Healthcare Professional Question Database

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Date Question  
Jan. 31, 2017What is the safety profile of Estrosmart? details
 

Response: The recommended dose by the manufacturer is 4 capsules per day. If taking 4 capsules of Estrosmart daily, the intake will include:
3,3'-Methylenebis-1H-indole (common name = indole-3-carbinol [I3C]): 100 mg
3-Hydroxymethylindole (common name = diindolylmethane [DIM]): 300 mg
Broccoli: 400 mcg
Green Tea (50% EGCG, no caffeine): 200 mg
Turmeric: 100 mg
Calcium D-glutarate 300 mg
Rosemary 50 mg

Safety with respect to dose/amount of each active ingredient:
The only evidence of broccoli is from dietary intake so there is no relevant safety information. No dosing recommendations are available for calcium-D glutarate.(4)
Some evidence suggests doses of I3C <200 mg daily can be used safely for up to 15 months.
Two studies have looked at DIM: the first used 2 mg/kg/day x 12 weeks with no problem.(1) The 2nd was a dose escalation study starting at 75 mg PO BID and ending with 300 mg PO BID.(2) Adverse effects were mild, though 2 of 4 patients taking 300 mg BID developed asymptomatic hyponatremia. As such, 225 mg PO BID was considered the appropriate dose for phase II trials; the amount in estrosmart is well below this amount.
The amounts of turmeric and rosemary in the recommended daily dose are much lower than usual doses (1g daily and 4-6g daily, respectively).(4)
Similarly with green tea, products tend to provide 75-400 mg epigallocatechin-3-gallate EGCG daily; this product’s EGCG content is 25 mg (50%). (4)
Adverse Effects(4)
The ingredients are well-tolerated.(4) Rash has been reported following I3C. Note the asymptomatic hyponatremia discussed above with DIM. Gastrointestinal adverse effects such as dyspepsia, diarrhea, and GERD have been associated with turmeric, though the low dose in this product will likely reduce incidence of these. Most adverse effects of green tea are on account of the caffeine content and this product is caffeine-free. No general adverse effects are documented for calcium-D glutarate or rosemary.
Interactions (4)
Due to the potential hyponatremic effect of DIM, use with caution in combination with diuretics or other drugs that can cause/exacerbate hyponatremia. Green tea (catechins), turmeric, and rosemary potentially have anticoagulant/antiplatelet effects. The interactions are theoretical, and this product contains very low doses of these ingredients, so they may not be as great of a concern. Green tea and rosemary may reduce absorption of dietary iron; the one study incorporated the extracts into the food and seems to exert the effect on release of heme-iron from the food.(3) Theoretically calcium-D glutarate may increase the clearance of drugs that undergo glucuronidation (e.g. acetaminophen, atorvastatin, diazepam, digoxin, lamotrigine, lorazepam, lovastatin, morphine, oxazepam).
Efficacy
The effectiveness of these ingredients has been made by extrapolating in vitro data.
References: 1.Del Priore G., Gudipudi, D. K., Montemarano, N., Restivo, A. M., Malanowska-Stega, J., and Arslan, A. A. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol.Oncol. 2010;116(3):464-467.
2.Heath, E. I., Heilbrun, L. K., Li, J., Vaishampayan, U., Harper, F., Pemberton, P., and Sarkar, F. H. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3'- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am.J.Transl.Res. 2010;2(4):402-411.
3.Samman S, Sandstrom B, Toft MB, et al. Green tea or rosemary extract added to foods reduces nonheme-iron absorption. Am J Clin Nutr 2001;73:607-12.
4. Ulbricht K, Basch E, editors. Online Natural Medicines[Internet]. Somerville (MA); c2017 [cited 14 Feb 2017]. Available from: https://naturalmedicines.therapeuticresearch.com/ Subscription required.

Feb. 8, 2017What are some potential reasons why phenytoin levels may increase or decrease? What is the best way to achieve a dose between 300mg-400mg daily using the 100mg capsules only? details
 

Patient Age: 83
Patient Sex: M
Medical Problems: Seizure disorder - last documented seizure 4 years ago
Serum albumin: 35 g/L
Total phenytoin: 30 umol/L
Medication History: Dilantin capsules 300 mg daily
spironolactone, furosemide, venlafaxine, warfarin, lorazepam
Response: Some potential factors causing reduced phenytoin levels might include (3):
- non-adherence
- ethanol intake; while it is thought acute heavy intake of ethanol will cause enzyme inhibition (and potentially increased phenytoin levels), this was not demonstrated in a single-dose kinetic study. (5) In terms of reduced levels, a kinetic study has demonstrated patients who drink at least 200g ethanol daily require higher phenytoin doses to maintain the same serum concentrations as non-drinkers. (5) However, this would mean the patient just recently started drinking heavily (upwards of 14 drinks per day) (6) on a daily basis.

Every other day dosing such as 300 mg alternating with 400 mg is a viable option.(4) As an alternative, give 3 x 400 mg doses per week on M, W, F with 300 mg given on the remaining days. A Monday morning trough level should give the trough of the whole week (since it's the only day with two consecutive days of 300 mg doses).
References: 1. http://www.globalrph.com/conv_si.htm#Parathyroid
2. http://clincalc.com/phenytoin/correction.aspx
3. http://mentalhealth.com/home/rx/phenytoin.html
4. Bauer LA. Phenytoin/Fosphenytoin. In: Bauer LA. eds. Applied Clinical Pharmacokinetics, 3e. New York, NY: McGraw-Hill; 2015. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1374§ionid=74720536. Accessed February 09, 2017.
5. Stockley's
6. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/what-standard-drink

Feb. 8, 2017What is the dosing regimen for amoxicillin, omeprazole, and clarithromycin for treating H. pylori in a child? details
 

Patient Age: 10
Medical Problems: H Pylori
Response: Amoxicillin:
25 mg/kg BID (max 2000 mg per day) (1,3)
Clarithromycin:
7.5 mg/kg BID (1) or
10 mg/kg BID (max 500 mg) (3)
Omeprazole:
0.5-1 mg/kg BID (max 20 mg) (1,3)
Best to treat children for 14 days. (2)
References: 1) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724145/table/t3-pch09709/
2) http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Hpylori.pdf
3) Lexi-peds

Feb. 8, 2017How do you treat arthritic pain in a hemochromatosis patient who has a contraindication for medications extensively metabolized by the liver (such as acetaminophen)? Would Gabapentin be a potential option? details
 

Patient Age: 58
Patient Sex: F
Medical Problems: hemochromatosis - told to avoid APAP but has not been told has any actual liver disease/damage
Response: Arthropathy is a common manifestation of hemochromatosis (HC) (1,4,12,13) that is generally not relieved by phlebotomy. (2, 6,12,13,15,16) The only information regarding treatment are statements in review articles in which options for arthritis are considered: NSAIDs (2,6,15) and intra-articular glucocorticosteroids (2,6,15,16). Colchicine may be used acutely as well if the cause of pain is seemingly pseudogout (6,15), and possibly at low dose for maintenance. (2,15,16) Short term systemic steroids are also considered. (2) APAP was only specifically listed in one paper, (15) though other papers refer to use of usual analgesics in general. (2,6,16) Toxicity from APAP occurs when there is not enough glutathione to bind to the intermediate and toxic metabolite, NAPQI. (8) Nothing directly states that APAP should not be used in HC; however, some preliminary research in animals suggests APAP toxicity may be potentiated by higher iron levels. (11) A clinical trial of anakinra for HC arthritis requires patients to have used and failed/not tolerated at least one month of maximal dose weak opioids, NSAID, colchicine, steroid injection, or a combination of the treatments. (13)
As for gabapentin, considering these are arthropathies, neuropathic agents would not be expected to be effective; there was no mention of use of neuropathic agents in any of the readings.
Therefore, if the arthropathy is akin to pseudogout, colchine would be reasonable for both acute attacks and long term. Also considered for acute attacks can be NSAIDs and intra-articular steroid injections. For non-pseudogout arthropathy, NSAIDs, intra-articular steroid injections (if confined to minimal joints), or short-term systemic steroids may be possibilities. Certainly each of these can cause long-term adverse effects; the lowest possible dose taken as infrequently as possible should be used.
References: 1. UTD - Clinical manifestations and diagnosis of hereditary hemochromatosis
2. UTD - Rheumatic manifestations of hereditary hemochromatosis
4. Lawrie PW. Hemochromatosis. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015. http://accessmedicine.mhmedical.com/content.aspx?bookid=1130§ionid=79754178. Accessed February 08, 2017.
6. https://www.hindawi.com/journals/arthritis/2014/375202/
7. https://gi.org/guideline/diagnosis-and-management-of-idiosyncratic-drug-induced-liver-injury/
8. http://emedicine.medscape.com/article/169814-overview#showall
11. https://academic.oup.com/toxsci/article/118/1/119/1661933/Iron-Potentiates-Acetaminophen-Induced-Oxidative
12. http://www.academia.edu/17265556/Arthritis_of_hemochromatosis
13. https://clinicaltrials.gov/ct2/show/NCT02263638
15. http://www.physicianspractice.com/articles/identifying-and-managing-hemochromatosis-arthropathy
16. Miscellaneous non-inflammatory musculoskeletal conditions. Haemochromatosis: the bone and the joint. Guggenbuhl P, Brissot P, Loréal O. Best Pract Res Clin Rheumatol. 2011 Oct;25(5):649-64. doi: 10.1016/j.berh.2011.10.014. Review. PMID: 22142745

Feb. 9, 2017If a patient has experienced anaphylactic reaction to ibuprofen in the past and has now been prescribed sulfasalazine, is there a potential for a cross-reaction? details
 

Response: There has only been one case report of sulfasalazine use in a patient with reported NSAID (ibuprofen) allergy.(4) Unfortunately, the details of the reported allergy were not documented and the child was not provided a challenge dose of sulfasalazine, rather they pre-emptively desensitized; as such, it cannot be known if the child would have also reacted to a therapeutic dose of sulfasalazine.(4) Considering ASA/NSAID reactions are related to COX inhibition, subsequent release of histamine, and synthesis of leukotrienes, a mechanistic phenomenon that has not been observed with 5-ASA is by inhibiting prostaglandin E2 and leukotrienes. (4) Furthermore, if this were a true IgE mediated reaction, it is specific to ibuprofen. (4,5) However, because the absence of reports does not prove it is not possible, to be prudent, a supervised test dose is a reasonable strategy. (4,5)
References: 4. Poh J, Knowles S. Safety of 5-Aminosalicylic Acid Derivatives in Patients with Sensitivity to Acetylsalicylic Acid and Nonsteroidal Anti-inflammatory Drugs. The Canadian Journal of Hospital Pharmacy. 2014;67(1):35-38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952906/
5. https://www.aaaai.org/ask-the-expert/mesalamine-nsaid

Feb. 9, 2017What are potential iatrogenic causes of anisocoria? details
 

Medical Problems: diffuse large B cell lymphoma
anisocoria x couple of months (may have been just noticed today)
atrial fibrillation
propranolol --> metoprolol Feb 2
loperamide new
apixaban --> Jan 17
a fib (relatively recent diagnosis)
Medication History: tazocin (feb 3), Vancomycin (Feb 7)
alendronate/Vit D weekly, apixaban (started Jan 17), Dilaudid, folic acid, metoprolol(switched from propranolol Feb 2), mirabegron 50 mg, pantoprazole, perindopril, prednisone 10 mg od, pregabalin
PRNs: APAP (none recently), dimenhydrinate, Buscopan (just started today), loperamide (had a few doses post-chemo), lorazepam, metoclopramide, Zofran
Post archop (day 22)
Response: Drug-induced anisocoria has been reported, and it is often due to anticholinergic drugs. (3,4,6) Most cases follow direct contact with the eye (3,14), such as removing a scopolamine patch and touching the eye (9,11) or several cases of misdirected ipratropium nebulization contacting one eye only. (7,10,12) There is one case in which perioperative systemic anticholinergic administration of IV butylscopolamine appeared to be the cause of anisocoria; though the author of this report was unsure as to why only one pupil had been dilated, not both. (13)
If the anisocoria occurs more in light environments, the large pupil is abnormal; if no ptosis/ophthalmoplegia, application of graded pilocarpine to the dilated eye can help confirm pharmacological causes. The recommendation is to use 0.1% first, and if there is no constriction, apply 1%. If there is still no or minimal constriction, it is likely pharmacological anisocoria. (3,14)
References: 1. http://sideeffects.embl.de/se/C0003079/
2. DrugDex
3. UTD - Approach to the patient with anisocoria
4. http://emedicine.medscape.com/article/1158571-clinical#b5
6.https://www.google.com/url?q=http://www.aaopt.org/sites/default/files/userfiles/outlines/outline25402.DOC&sa=U&ved=0ahUKEwj92cKmlobSAhUE2WMKHT94DxM4FBAWCBMwBw&client=internal-uds-cse&usg=AFQjCNENOjWGtTI55L_Zg6dxTwfZCm05zA
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159376/
9. Acute pupil asymmetry in a 6-month-old boy. Diagnosis: pharmacologic anisocoria. Osorio MJ, Zuckerbraun NS, Painter M. Pediatr Ann. 2009 Nov;38(11):622-4, 627. doi: 10.3928/00904481-20091016-07. No abstract available. PMID: 19968207
11. Transdermal scopolamine and perioperative anisocoria in craniofacial surgery: a report of 3 patients. Lee DT, Jenkins NL, Anastasopulos AJ, Volpe AG, Lee BT, Lalikos JF.
J Craniofac Surg. 2013 Mar;24(2):470-2. doi: 10.1097/SCS.0b013e318275ec4a. PMID: 23524718
12. PubMed: "anisocoria anticholinergic"
13. Transient anisocoria after intravenous administration of butylscopolamine. Kiyama S. Anesth Analg. 1991 Jul;73(1):97-8. No abstract available. PMID: 1859001
14. Anisocoria after open reduction and internal fixation of a mandible fracture under general anesthesia: a case report. Jarmoc M, Shastri K, Davis F. J Oral Maxillofac Surg. 2010 Apr;68(4):898-901. doi: 10.1016/j.joms.2009.02.010. No abstract available. PMID: 20022156

Feb. 9, 2017Is Cymbalta a good choice for treating anxiety with concurrent chronic pain in multiple sites? details
 

Patient Sex: F
Medical Problems: chronic pain
anxiety
Response: There is some literature of duloxetine in adolescents and pieced together, it seems a reasonable agent to trial.
Three fairly large trials have been conducted in adolescents for the treatment of depression. (6,8,9) These trials used placebo and fluoxetine comparators, included over 1000 adolescents (n=476 received duloxetine, n= 234 received fluoxetine) and assessed efficacy, safety, and pharmacokinetics.
Pharmacokinetics: conclusions from the study in 72 children between the ages of 7 and 17 were that "adjustment of total daily dose based on body weight or age is not warranted for pediatric patients, and different total daily doses may not be warranted for pediatric patients relative to adults." (6)
In terms of safety: no changes in ECG (8), blood pressure (9) or laboratory abnormalities were identified. (8,9) Pulse did increase on average 4 bpm in the duloxetine group compared to a reduction of 1.3 bpm in the fluoxetine group in the second trial. (9) Furthermore, a total of five patients in the duloxetine group sustained elevations in blood pressure compared to none in the fluoxetine group. (9) No differences in suicidal ideation (9) or worsening suicidal ideation (8) were reported compared to placebo. (8) However, in the first study, 2.7% in the duloxetine compared to 0.9% and 0.8% in the fluoxetine and placebo groups, respectively, had treatment-emergent suicidal behaviour during the 36 week study; (8) no differences were found in the second study. (9) Treatment-emergent adverse effects (not detailed) and drop outs due to adverse effects occurred more frequently in the duloxetine 60 mg group, but not the duloxetine 30 mg group in the first trial. (8) Conversely, no differences in these outcomes were reported in the second trial. (9)
In terms of efficacy: neither duloxetine nor fluoxetine demonstrated effectiveness compared to placebo. (8) However, keep in mind these trials were in pediatric depression. One trial in generalized anxiety has been conducted that enrolled 272 youth aged 7 through 17 years (n=135 duloxetine). (7) This trial included a 10 week placebo-controlled phase followed by an 18 week open-label extension. Following the first 10 weeks, duloxetine demonstrated a statistically significant improvement in GAD compared to placebo. This trial was designed for flexible dosing (30 mg-120 mg daily); the mean dose in the acute phase was 53.6 mg and 63.2 mg in the extension phase.
There appear to be no trials assessing the use of duloxetine for pediatric pain. Three case reports are available in which duloxetine (final doses of 40 mg (4) and 60 mg (5)) seemed to provide significant benefit for pain in a 13(4), 14(4) and 10 year old(5), respectively.
References: 1. UTD - Evaluation and management of pain in children
2. UTD - Pharmacotherapy for anxiety disorders in children and adolescents
3. UTD - Pediatric unipolar depression and pharmacotherapy: Choosing a medication
4. Meighen KG. Duloxetine treatment of pediatric chronic pain and co-morbid major depressive disorder. J Child Adolesc Psychopharmacol 2007; 17:121. PMID 17343560
5. Desarkar P, Das A, Sinha VK. Duloxetine for childhood depression with pain and dissociative symptoms. Eur Child Adolesc Psychiatry 2006; 15:496. PMID 16732464
6. Clin Pharmacokinet. 2014 Aug;53(8):731-40. doi: 10.1007/s40262-014-0149-y. Pharmacokinetics of orally administered duloxetine in children and adolescents with major depressive disorder. Lobo ED1, Quinlan T, Prakash A. PMID 24989060
7. Strawn JR, Prakash A, Zhang Q, et al. A randomized, placebo-controlled study of duloxetine for the treatment of children and adolescents with generalized anxiety disorder. J Am Acad Child Adolesc Psychiatry. 2015 Apr;54(4):283-93. doi: 10.1016/j.jaac.2015.01.008. Epub 2015 Jan 29. PMID 25791145
8. Emslie G, Prakash A, Zhang Q, et al. A double-blind, efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2014;24(4):170–9.
9. Atkinson SD, Prakash A, Zhang Q, et al. A double-blind, efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2014;24(4):180–9.

Feb. 10, 2017My patient with MS (who takes Tecfidera) is wondering if it's safe to use CBD hemp oil. details
 

Patient Age: 41
Patient Sex: F
Medical Problems: M.S.
Anxiety
stomach problems
Medication History: Tecfidera
Response: Currently, there is no evidence for a drug-drug interaction between Tecfidera and hemp oil. (1,2,3). Potentially an interaction could occur and hemp oil should be used with caution. Tecfidera causes immunosuppression and hemp oil studies in mice have also shown some immunosuppressive properties. (2) Therefore we may suspect potentially greater immunosuppression with the combination. Safety data currently says hemp oil use is likely safe in adults, but there is no evidence to suggest efficacy in treating any condition. (2) There may be greater risk than benefit in this case. Depending on what the hemp oil is being used for, it may be more appropriate to consider alternative therapy.
References: 1. AHFS® Drug Information. Lexi-Comp Online, Bethesda, MD: American Society of Health-System Pharmacists; 2017; accessed 13 Feb 2017
2. Ulbricht K, Basch E, editors. Online Natural Medicines[Internet]. Somerville (MA); c2017 [cited 13 Feb 2017]. Available from: https://naturalmedicines.therapeuticresearch.com/ Subscription required.
3. Ogbru O, Abedin S, editors. RxList. San Clemente, CA: WebMD; c2017 [cited 13 Feb 2017]. Available from: http://www.rxlist.com

Feb. 10, 2017If a patient has failed to have clinical success on a 10-day course of amoxicillin for Scarlet fever, and erythromycin is unavailable as an alternative, what may be some other alternative options for therapy? details
 

Patient Sex: 5
Medical Problems: NKA
no meds
20.8 kg
Medication History: Amoxicillin x 10 days, rash, sore throat persist
Response: While there would be no reason to continue treatment based on the rash alone (1), considering the continued presence of sore throat, further treatment may be warranted. Azithromycin and clindamycin are alternative treatments (2) though resistance is consdierable in Canada.(3) Cephalopsorins are also an alternative, but considering it is another beta-lactam, it may not be the best choice.
Suggest
Azithromycin 20 mg/kg/d x 3 days (2,3) or 12 mg/kg.d x 5 days (2,4)
Or
Cephalexin 25-50 mg/kg/day div QID or cefuroxime-AX 20 mg/kg/day divied BID x 10 days (4)
References: 1. UTD - Complications of streptococcal tonsillopharyngitis
2. UTD - Treatment and prevention of streptococcal tonsillopharyngitis
3. Bugs and Drugs
4. MUMS app

Feb. 10, 2017Zoloft is contraindicated in those with closed-angle glaucoma. Are there any other safer SSRIs for use in patients with CAG? details
 

Medical Problems: closed-angle glaucoma
hyperthyroidism
Response: SSRIs/SNRIs appear on lists of drugs that can exacerbate CAG.(1,2) One article suggests it is due to anticholinergic properties.(2) Antidepressants without anticholinergic activity include bupropion, trazodone, venlafaxine, fluvoxamine, sertraline(3) though they all have a warning to evaluate patients for narrow-glaucoma if they have not had an iridectomy. (4)
More information is required. If the patient is at risk of CAG or for some reason the patient has CAG but cannot have surgery or patient is waiting for surgery, buprioprion may be suggested as it was not included in the lists of antidepressants associated with CAG close monitoring. (1, 2)
References: 1. UTD - Angle-closure glaucoma Table - Medications associated with acute angle-closure glaucoma (AACG)
2. A review of drug-induced acute angle closure glaucoma for non-ophthalmologists. Ah-Kee EY, Egong E, Shafi A, Lim LT, Yim JL. Qatar Med J. 2015 May 10;2015(1):6. doi: 0.5339/qmj.2015.6. Review. PMID: 26535174
3. Clinical Handbook of Psychotropic Drugs, pg 60
4. Lexicomp

Feb. 10, 2017My patient would like information on treatment options for primary progressive multiple sclerosis, including ocrelizumab, and stem cell transplant information. details
 

Patient Age: 37
Patient Sex: M
Medical Problems: primary progressive multiple sclerosis dianosed last year
Medication History: n/a
Response: Primary progressive MS lacks effective medical treatment, potentially due to the absence of inflammation, unlike relapsing MS (1). There are currently no approved medications for PPMS however some medications have shown potential including methotrexate, rituximab, ocrelizumab, and stem cell therapy. (2, 3)

A. Methotrexate has ambiguous evidence for use in PPMS and evidence stems from a single RCT. (4, 5, 6) Based on the single RCT, it is possible that methotrexate may slightly improve the disease course of PPMS through alteration of the immune system. (5, 7) However a Cochrane review, limited to the single RCT, concluded that there was a non-significant trend in reducing disability progression and number of relapses. (7) More research needs to be completed to determine if the efficacy of methotrexate in PPMS outweighs its side effects.

B. Rituximab may delay disease progression in patients less than 51 years old with PPMS. (3) The examination of rituximab in MS is referred to as the OLYMPUS trial and a subgroup analysis of patients less than 51 years old showed a delay in confirmed disease progression. (8) The proportion of patients with confirmed disease progression at 96 weeks was 30.2% rituximab vs. 38.5% placebo (rituximab n= 272 vs placebo n= 147). (4, 8)

C. Ocrelizumab is the first drug to show a significant reduced risk of disability progression among patients with PPMS as in the ORATORIO trial. The trial has shown modest reduction of disability progression (ARR 6% at 12 and 24 weeks, compared to placebo), slowed deterioration from baseline of a timed 25-foot walk, and improvements in MRI T2 lesion volume and whole brain volume loss. Compared to placebo, Ocrelizumab has been associated with more neoplasms, infusion reactions, upper respiratory tract infections, and oral herpes. (9) Ocrelizumab is not currently available in Canada and a phase 3 trial is expected to finish in 2021. (10)

D. Stem cell therapy has been used experimentally in those with aggressive or unresponsive MS. It has shown some evidence slowing MS disease activity and repairing damage in the CNS. However stem cell therapy has been shown to increase mortality by 1-2%. The procedure includes collecting patient stem cells followed by exposure to chemotherapy to deplete the immune system, as immune system dysfunction is thought to be causing the MS damage. There is currently no approved stem cell therapy treatment for MS and there needs to be further analysis on the risks vs benefits of SC treatment. (11)

Impairment due to MS, such as spasticity, mobility, tremor, pain, fatigue, urinary symptoms, depression, and anxiety may be managed through nonpharmacological and pharmacological therapy when needed. (3)
References: References:
1. MS Society of Canada. Progressive MS.[homepage on the internet] Toronto Ont: MS Society of Canada; [updated NA; cited 2017 Feb 13] Available from : https://mssociety.ca/hot-topics/progressive-multiple-sclerosis
2. Hoffman La-Roche. Media release: FDA extends review of application for OCREVUS [homepage on the internet]. Switzerland, Hoffmann La-Roche; [updated NA; cited Feb 13, 2017]. Available from: http://www.roche.com/media/store/releases/med-cor-2016-12-20.htm
3. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 116285, Multiple sclerosis (MS); [updated 2017 Jan 27, cited Saskatoon, Feb 13 2017]; [about 35 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=116285&site=dynamed-live&scope=site. Registration and login required.
4. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 905968, Disease-modifying therapies for multiple sclerosis; [updated 2017 Feb 03, cited Saskatoon, Feb 13 2017]; [about 29 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=905968&site=dynamed-live&scope=site. Registration and login required.
5. Goodin D, Frohman E, Garmany G, Halper J, Likosky W, Lublin F et al. Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002;58(2):169-178.
6. Goodkin DE, Rudick RA, VanderBrug Medendorp S, Daughtry MM, Schwetz KM, Fischer J, Van Dyke C. Low dose (7.5mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Annals of Neurology 1995;37:30-40
7. Gray O, McDonnell GV, Forbes RB. Methotrexate for multiple sclerosis. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD003208. DOI: 10.1002/14651858.CD003208.pub2
8. Hawker K, O'Connor P, Freedman M, Calabresi P, Antel J, Simon J et al. Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial. Annals of Neurology. 2009;66(4):460-471.
9. Olek, Michael J. Treatment of progressive multiple sclerosis in adults. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 13 Feb 2017. Available from www.uptodate.com. Subscription and login required
10. Clinicaltrials.gov. A study of ocrelizumab in participants with primary progressive multiple sclerosis [homepage on the internet]: Bethesda, MD: Clinicaltrials.gov. [updated Jan 6 2017: cited Feb 13 2017]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT01194570?term=ocrelizumab&rank=6&show_locs=Y#locn
11. MS Society of Canada. Stem Cells. [homepage on the internet]. Toronto Ont: MS Society of Canada; [updated NA; cited 2017 Feb 13] Available from: https://mssociety.ca/hot-topics/stem-cells

Feb. 10, 2017We have rx for nitrofurantoin for a breastfeeding woman with UTI. My research suggests nitrofurantoin may be of concern. Is there any more data? What alternatives are available. details
 

Medical Problems: infant = 10 days old, 5 days out of NICU
NKA
maternal UTI
Medication History: nothing, no antibiotics in last year
Response: While it appears nitrofurantoin may be safe for maternal use in breastfeeding infants at least 8 days' old (1), this infant is just on the cusp and spent his first 5 days in NICU. Based on information below, consider trimethoprim alone or cephalexin.

Alternatives and safety in nursing:
Fosfomycin is 1st line, (2,3) however, due to limited information about use in breastfeeding infants, it is considered to be “likely safe,” especially if infant is 2 months old. (1)
Cephalexin is an alternative for 1st time cystitis with no antibiotic exposure in the last 6 months. (2) There are low levels detected in breastmilk, but it can possibly cause diarrhea/thrush in the breastfeeding infant. (1,3)
TMP/SMX is an alternative for 1st time cystitis and no antibiotic exposure within last 6 months. (2) It is acceptable after the newborn period (i.e. 1 month of age). (1)
Ciprofloxacin is an alternative for 1st time cystitis and no antibiotic exposure within last 6 months. (2)It is traditionally not used because of concerns regarding infant joint development. It's possible the calcium in the breastmilk may bind ciprofloxacin, thereby reducing exposure to the infant. Use in nursing mothers is acceptable with monitoring of the infant for diarrhea or thrush, and avoiding breastfeeding for 3-4 hours after a dose to decrease the exposure. (1)
Trimethoprim is found in low levels in breastmilk; it is not a concern.(1,3)
References: 1. Lactmed
2. Bugs and Drugs app
3. MUMS app

Feb. 13, 2017Can pregabalin or gabapentin be used in a patient on peritoneal dialysis (eGFR 5-7 ml/min)? details
 

Medical Problems: GFR 5-7 ml/min
Response: For both pregabalin and gabapentin, patients on peritoneal dialysis should be dosed as though CrCl < 15 ml/min.(4) Starting doses of gabapentin 50-100 mg once daily (1,2,4) or 25 mg pregabalin (1,2,4) once daily would be appropriate. Suggested maximum dose of pregabalin is 75 mg once daily. (1,2)
References: 1. Lexicomp
2. DrugDex
3. Dialysis of Drugs 2013
4. Renal Drug Handbook

Feb. 13, 2017My patient received a prescription for metoprolol 25 mg PO BID for benign PVCs. I am unsure if the cardiologist is aware her resting HR is 50-55 and resting BP is 112/68. Will metoprolol further reduce her HR and BP, making her feel worse? She also takes Neo-40, a natural product formulated of nitric oxide. Could it be contributing to her low HR and BP? details
 

Medical Problems: PVCs - not bothering her went on antibiotic in December and they flared, then resolved after antibiotic was stopped
Medication History: Pantoloc, zopiclone, premarin cream, Flonase, Ditropan
Response: The main treatment for PVCs is treating the underlying structural heart disease/ symptoms, if present.(1) For those with no structural disease but bothersome symptomatic PVCs, beta blockers may be useful, though have not been shown to improve survival in this population.(1) Certainly beta blockers can be expected to reduce heart rate(2,3), though this is less pronounced with beta blockers with ISA;(2) Metoprolol is not ISA positive.(3)
The formulation of Neo 40 is only available on the website as a 'patented formula' with Vitamin C and Vitamin B12.(4) One of the referenced studies included ingredients: beet root extract, hawthorn berry, vitamin C, L-citrulline, and sodium nitrite.(6) Hawthorn berry and L-citrulline theoretically can cause additive hypotension (7); however, the only ingredient that has any sort of evidence is hawthorn berry (it may be possibly effective for angina and HF).(7) One small pilot trial suggests the product may lower BP more than placebo with no change in heart rate, though the methodology is weak to make any firm conclusions. (5)
Therefore, it is possible the Neo40 is contributing to lower blood pressure. The metoprolol is likely to further reduce heart rate and it seems important to clarify if the cardiologist is aware of the patient's resting HR.
References:
1. UTD - Ventricular premature beats
2. UTD - Major side effects of beta blockers
3. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-HTN-bb.pdf
4. http://neogenis.ca/#/faq
5. http://neogenis.ca/articles/Prehypertension-Clinical-Trial.pdf
Biswas O, et al. Effects of an Oral Nitric Oxide Supplement on Functional Capacity and Blood Pressure in Adults With Prehypertension. J Cardiovasc Pharmacol Ther. 2014
6. http://neogenis.ca/articles/JCH%20final%20proofs.PDF
Houston M, et al. Acute Effects of an Oral Nitric Oxide Supplement on Blood Pressure, Endothelial Function, and Vascular Compliance in Hypertensive Patients. J Clin Hyper. 2014
7. Natural Medicines

Feb. 14, 2017I have a patient who takes up to 40 mg per day of ondansetron due to nausea associated with anxiety. Other than ECG changes and risk of serotonin syndrome, is there any information on the safety of long term ondansetron overuse? details
 

Response: Oral ondansetron is typically used for chemotherapy-induced nausea and vomiting at the dose of 8 mg PO twice daily for 3 days and highly emetogenic chemo has been dosed up to 24 mg PO 30 minutes before starting treatment. (1) Acute overdose of ondansetron has caused fever, rash, pruritus, restlessness, CNS depression, seizures, tachycardia, elevated liver enzymes, hypotension and temporary blindness. (1) Ondansetron, as a serotonergic agent, is also known to cause agitation (oral: ≤6%) and anxiety (oral: ≤6%). (2)
One case study describes a 25 year old man taking up to 40 x 4 mg ondansetron tablets per day for a week for nausea and vomiting following gastric bypass. The patient was admitted with severe headache of a week’s duration and imaging showed acquired cerebral edema, later experiencing near blindness and an intracranial hemorrhage. In this case it was recognized as posterior reversible encephalopathy syndrome which describes changes in neuroimaging potentially due to impaired cerebral blood flow and endothelial dysfunction. (3)
No human data is available regarding potential cumulative effects of chronic use of high dose ondansetron. The monograph describes animal studies in which dogs given oral ondansetron, at 7.5-25 mg/kg/day for 5 weeks, exhibited behavioral depression (at highest dose levels). In rats and mice, there was no evidence of tumourgenic effects with high-dose ondansetron taken for 2 years. (4)
Overall, there is limited safety evidence for chronic high dose ondansetron use.
References: 1. DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/ (cited: Feb/14/2017).
2. Lexi-Comp OnlineTM , Lexi-DrugsTM , Ondansetron, Hudson, Ohio: Lexi-Comp, Inc.; 2017; February 14, 2017.
3. Toxnet Toxicology Data Network. Hazadrous Drugs Data Base (HSBD) [homepage on the Internet]. Ondansetron. Bethesda, MD: U.S. National Library of Medicine; [updated 2016 Oct 25; cited 2017 Feb 14]. Available from: https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~GsRvmM:3
4. Product Monograph (not online). Product monograph for Ondansetron. Actavis Pharma Company. Mississauga, ONT. L5N 6J5. February 2017.

Feb. 14, 2017Is a washout period required when switching from Neupro patch to ropinirole? details
 

Patient Age: 64
Medication History: levocarb, amantadine
Response: Most studies address the switch from oral treatment to the patch. (2-4) While there was no report of how patients tolerated the switch, one study employed an overnight switch with patients changing from rotigotine patch to oral ropinirole or oral pramipexole.(5) Those switching to ropinirole did so at a 1:1 dose conversion.(5) This seems reasonable given the plasma levels decrease with a terminal half-life of 5-7 hours following patch removal.(1)
References: 1. eCPS - Neupro
2. Winkelman JW, Mackie SE, et al. A method to switch from oral dopamine agonists to rotigotine in patients with restless legs syndrome and mild augmentation. Sleep Med. 2016 Aug;24:18-23.
3. Kim HJ, Jeon BS, Lee WY, et al. Overnight switch from ropinirole to transdermal rotigotine patch in patients with Parkinson disease. BMC Neurol. 2011 Aug 10;11:100.
4. eWitt PA, Boroojerdi B, MacMahon D, et al. Overnight switch from oral dopaminergic agonists to transdermal rotigotine patch in subjects with Parkinson disease. L
Clin Neuropharmacol. 2007 Sep-Oct;30(5):256-65.
5. Chitnis S, Jaffery M, Dewey RB.Outcomes from switching from rotigotine patch to alternate therapies in Parkinson's disease. Int J Neurosci. 2012 Jan;122(1):22-5.

Feb. 14, 2017Are there any contraindications to give emergency contraceptive pills in a patient who has a copper IUD? details
 

Response: There are no contraindications to give ECP in the presence of a copper IUD. (1) It is likely not required in this case as copper IUDs are also used as a form of emergency contraception and are more effective than hormonal emergency contraception. (1) Educating the patient on the role of copper IUDs for emergency contraception may help reduce their anxiety.
References: 1. SOGC - Emergency Contraception 2012

Feb. 14, 2017My patient’s cardiologist prescribed dabigatran 110 mg BID as they are experiencing symptoms of atrial fibrillation again after being cardioverted 10 years ago. My software says verapamil (and theoretically diltiazem) increases dabigatran levels, what is the significance of this? My patient also has a history of GI bleeds (currently on pantoprazole) so increased dabigatran levels is concerning. details
 

Patient Age: 64
Patient Sex: M
Medical Problems: atrial fibrillation - converted 10 years ago, symptoms recurring
(has been to many specialists and had surgeries over the years)
hx GI bleed -
normal renal function
Medication History: diltiazem 30 mg up to TID, depending how feels (see notes in med problems)
furosemide, opioids, pantoprazole, zopiclone, trazodone, levothyroxine
T3, hydromorphone
topical testosterone
Response: Documentation of elevated dabigatran levels secondary to verapamil exists(1); despite this, no dose adjustment is recommended.(2) There is no documentation of the interaction with diltiazem.(1) It appears the MD has considered patients bleed risk and reduced dose to 110 mg po BID as suggested in the monograph (2). Pantoprazole, which not only acts as a gastic protectant, may actually reduce dabigatran levels, however no dose adjustment is recommended.(2) Considering all of these factors, the risk of bleeding does not appear to outweigh the anticoagulant benefits.
References: 1. Stockley's
2. eCPS - Pradaxa

Feb. 16, 2017Is a taper required for this prescription: Prednisone 50 mg po OD for 10 days? details
 

Medical Problems: Language barrier but caller thinks a TB treatment protocol caused something with platelets
Response: Risk of adrenal suppression (nausea, fatigue, shortness of breath, hypotension, hypoglycemia, myalgia, fever, dizziness) is low if systemic steroids are taken less than 3 weeks. (1,2,3) One may want to consider a short tapering course if there is risk of disease flare (e.g. autoimmune, poison ivy), or patient is ill or frail.(1,2,3)
References: 1. Canadian Pharmacist's Letter 2010; 26(5):260507
2. https://aacijournal.biomedcentral.com/articles/10.1186/1710-1492-9-30
3. eCPS - CPhA Monograph - Corticosteroids: Systemic
4. GeriRx Files, pg 178

Feb. 16, 2017What is unfractionated heparin? details
 

Response: Unfractionated heparin is the same as heparin (1). It is unlike low molecular weight heparins which would be ordered as the brand (eg. Innohep) or generic name (eg. tinzaparin).
References: 1. eCPS - CPhA Heparin: Unfractionated

Feb. 16, 2017Are there any drug interactions or generally harmful contents in this product? Any concerns with use in a patient with coronary artery disease? Product in question contains (serving size per 4 capsules): A. Proprietary testosterone support complex 2.1 g [containing Testofen - Trigonella foenun greacum (fenugreek) seed, Trigotest - Trigonella foenun greacum (fenugreek) seed, and Tribulus.] B. Proprietary DHT support complex 280 mg [containing saw palmetto extract, stinging nettle] C. Proprietary estrogen support complex 150 mg [containing hesperidin, apigenin , and resveratrol] D. Pyridoxine 10.5 mg E. Mg 90 mg F. Zinc 30 g details
 

Patient Age: 60
Patient Sex: M
Medical Problems: apigenin
fenugreek
hesperidin
resveratrol
saw palmetto, stinging nettle
tribulus
Medication History: Ticagrelor, ASA, metoprolol and atorvastatin. An Ace inhibitor will likely be started in next 24-48 hours.
Response: None of my references have any information about apigenin. (1-6) Fenugreek (1-5), or saw palmetto (1,3-5).

Saw palmetto may inhibit 3A4 but this was not documented when 3000 mg daily was taken for 8 weeks.(1) The concise dose of saw palmetto is indeterminable from the labelling but it would be no more than 280 mg per 4 capsules. Saw palmetto may have cardiovascular concerns. (1) NMCD states, “Occasional occurrences of hypertension, tachycardia, angina pectoris, arrhythmia, extra systole, angiopathy, myocardial infarction, and congestive heart failure have been noted in the clinical literature in association with oral saw palmetto use, although these reports have provided limited information to determine causality”.

Possibly resveratrol(1,4) and hesperidin(1) increase bleeding risk. Stinging nettle (1,4) and tribulus (1.4) may have hypotensive effects. None of the ingredients were considered harmful in general.(1-5)
References: 1. Natural Medicines - DI checker
2. Natural Medicines - monographs
3. Lexicomp
4. Micromedex
5. About Herbs
6. DerMarderosian A, McQueen C, eds. 2016. Review of Natural Products, The. St. Louis, MO. Facts and Comparisons® Publishing Group. ISSN 1089-5302. STAT!Ref Online Electronic Medical Library. http://online.statref.com/Document.aspx?docAddress=DpksYdH8U_LRqcmPeRdKIQ%3d%3d. 2/16/2017 10:45:01 AM CST (UTC -06:00).

Feb. 21, 2017What is the prednisone equivalent of oral budesonide? Our patient is not responding to budesonide at a daily dose of 9 mg. Her MD has a sense of what prednisone dose is effective for her so wants to know the equivalent. details
 

Patient Sex: F
Response: Unlike other glucocorticoids, no well-established equivalent dose to prednisone is available for oral budesonide. However, in trials comparing oral prednisone to oral budesonide, 40 mg prednisone and 9 mg budesonide (1) or 10 mg (2,3) have resulted in similar remission rates of Crohn’s disease.
References: 1. National Advisory Committee on Immunization. Update on the use of herpes zoster vaccine. Public Health Agency of Canada. 2014 Jan. Available at http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-92-2014-eng.pdf . Accessed 2014 Mar 14.
2. Roth M, Gross V, Scholmerich J, Ueberschaer B, Ewe K. Treatment of active Crohn's disease with an oral slow-release budesonide formulation. Am J Gastroenterol 1993; 88: 968-9.
3. Rutgeerts P, Löfberg R, Malchow H, et al. A comparison of budesonide with prednisolone for active Crohn’s disease. N Engl J Med 1994; 331: 842-5

Feb. 21, 2017Is there any evidence for lysine to prevent HSV-2? (We know there is some for HSV-1). details
 

Response: There is some research suggesting lysine may prevent recurrent HSV infection(3,4,13,14) and that it appears to be dose-dependent.(4,13,14) Generally, HSV-1 causes orofacial lesions and HSV-2 causes genital lesions; that said, HSV-1 can less commonly be the pathogen.(11) The only trial that included patients with genital herpes is not available for review.(3) The abstract does not report how many of the patients had genital HSV, if the strains were typed, and of those with gential HSV, how many experienced positive results.(3) Another study that included patients with genital herpes was a survey inquiring about subjective improvement of episodes following lysine supplmentation. All of the limitations of the former trial apply as well as methodological limitations of a survey.(17)
The proposed mechanism of lysine is that it acts as an antagonist of arginine, which is required for herpes simplex virus replication.(6,8,9) HSV-2 also relies on arginine for replication.(8) Considering the typical daily dietary intake of lysine is 6-10 g and the usual dose is 1000 mg PO TID, serious adverse effects are not expected.(4) Adverse effects that have been reported include abdominal pain and diarrhea with daily doses of 10 g; a more serious event is that of Fanconi's syndrome reported in one patient who took 3000 mg daily for 5 years.(4,18)
Therefore, while there is no clincial evidence lysine will be effective to prevent genital herpes, risks are low should the patient still want to try it.
References: 1. Beauman JG. Genital herpes: a review. Am Fam Physician. 2005 Oct 15;72(8):1527-34. Review. PMID: 16273819
2. Groves M. Genital herpes: a review. Am Fam Phys. 2016; 93(11):928-934.
3. Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. 1987;175:183–90.
4. http://www.medscape.com/viewarticle/406943_5
5. http://www.altmedrev.com/publications/12/2/169.pdf
6. Ara DerMarderosian, PhD, Cydney E. McQueen, PharmD, eds. 2016. Review of Natural Products, The. St. Louis, MO. Facts and Comparisons® Publishing Group. ISSN 1089-5302. STAT!Ref Online Electronic Medical Library. http://online.statref.com/Document.aspx?docAddress=nFetqneof3zaErDeI209Jg%3d%3d. 2/22/2017 8:40:10 AM CST (UTC -06:00).
7. Sen P, Barton SE. Genital herpes and its management. BMJ.2007;334(7602):1048-1052. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871807/
8. Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways.
Sanchez MD, Ochoa AC, Foster TP. Antiviral Res. 2016 Aug;132:13-25. doi: 10.1016/j.antiviral.2016.05.009. PMID: 27192555
9. Arginine inactivates human herpesvirus 2 and inhibits genital herpesvirus infection. Ikeda K, Yamasaki H, Minami S, Suzuki Y, Tsujimoto K, Sekino Y, Irie H, Arakawa T, Koyama AH. Int J Mol Med. 2012 Dec;30(6):1307-12. doi: 10.3892/ijmm.2012.1149. PMID: 23042569
10. National Center for Biotechnology Information. PubChem Compound Database; CID=5962, https://pubchem.ncbi.nlm.nih.gov/compound/5962 (accessed 22 Feb 2017).
11. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 114875, Genital herpes; [updated 2017 Feb 09, cited place cited date here]; [about 21 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=114875&site=dynamed-live&scope=site. Registration and login required.
12. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol. 1980; 60:85-7.
13. Thein DJ, Hurt WC. Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg. 1984; 58:659-66.
14. McCune MA, Perry HO, Muller SA et al. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis. 1984; 34:366-73.
15. DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infections. Arch Dermatol. 1984; 120:48-51.
16. Simon CA, Van Melle GD, Ramelet AA. Reply. (Failure of lysine in frequently recurrent herpes simplex infection.) Arch Dermatol. 1985; 121:167-8. Letter.
17. Walsh DE, Griffith RS, Behforooz A. Subjective response to lysine in the therapy of Herpes simplex. J Antimicrob Chemother 1983;12:489-496.
18. Natural Medicines

Feb. 22, 2017Does "Jian Pai cream" (NPH - 80038015) interact with any of the patient's current medications? (ingredients include: sophorae glavescentis, borneol, gromwell root, phellodednon bark) details
 

Patient Age: 84
Patient Sex: F
Medical Problems: Thoracic aneurysm/hypertensive urgency
Psoriasis (uses herbal cream for treatment)
Medication History: Acetaminophen, atorvastatin, gravol, docusate, labetalol, ramipril, zopiclone
Response: I found that two ingredients were also referred to as lithospermum (arnebia guttata or gromwell) and camphor (borneolum or zhang hao or bing pian) and used those in my drug interaction analysis. (1,2, 3, 4, 5) I was unable to include sophora flavenscens (Ku Shen or sophora root) in my drug interaction analysis on Natural Medicines as I could not find another name for the drug.
The analysis of lithospermum, camphor and phellodendron showed drug interactions with acetaminophen, atorvastatin, and labetalol. Camphor is potentially hepatotoxic and should be used with caution with concomitant acetaminophen, atorvastatin, and labetalol as there may be an increase in liver enzymes and risk of developing liver damage. Phellodendron and atorvastatin should be used with caution as phellodendron might inhibit CYP3A4 enzymes, potentially increasing levels of atorvastatin and other CYP3A4 substrates. (6)
Patient is using topical products which likely decreases the chance of significant drug interactions however due to the lack of evidence of drug interactions with this product it should be used cautiously or discontinued.
References: 1. https://www.sacredlotus.com/go/chinese-herbs/substance/zi-cao-groomwell-root-arnebia-lithospermum
2. https://www.sacredlotus.com/go/chinese-herbs/substance/bing-pian-borneol
3. http://acupuncturetoday.com/herbcentral/borneol.php
4. http://08hachi.blogspot.ca/2011/08/dryobalanops-aromatica-gaertn.html
5. https://www.sacredlotus.com/go/chinese-herbs/substance/zhang-nao-camphor
6. Natural medicines database interaction checkler: https://naturalmedicines.therapeuticresearch.com/#

Feb. 24, 2017Patient is switching from Warfarin to Eliquis 5mg BID. The literature states to initiate apixaban when INR is less than 2.0 When stopping warfarin, what is a reasonable estimate of how long it would take for INR to decrease to less than 2? Patient's last INR was 2.0 on Feb 13th, and is due to repeat on Monday Feb 27th. My plan was to have patient go for INR on the 27th, and depending on what the result was, discontinue warfarin for 48 hours (2 doses) and then initiate apixaban. details
 

Patient Age: 80
Patient Sex: F
Medical Problems: 200 lbs
Atrial Fibrillation
Diabetes Type 2
Hypertension
Medication History: Warfarin 3mg EOD with 4mg, Starting Eliquis 5mg BID
Metformin 1000mg BID
Lisinopril HCTZ 20/25mg OD
Metoprolol 200mg BID
Forixga 10mg OD
Glyburide 5mg OD
Trazodone 50mg HS
Venlafaxine 225mg HS
Digoxin 0.0625mg OD
Rosuvastatin 20mg OD
Response: NOACs have a rapid onset of action and patients should wait until INR is 2.0 or lower before starting a NOAC. If INR testing isn’t readily available, it is reasonable to wait 2-3 days after last warfarin dose before starting a NOAC. (1,2) In the the ROCKET AF trial the highest INR prior to transition was 3.0 for starting rivaroxaban and the highest INR was 2.3 in trials for switching to dabigitran (RE-LY, RE-SONATE, and RE-MEDY). (3) These trials showed no indication that overlap of therapy was associated with increased bleeding risk. (3)
References: 1. Thrombosis Canada: New/Novel Oral Anticoagulants (NOACs): Comparison and Frequently-Asked Questions. Accessed Feb 28 2017. http://thrombosiscanada.ca/?page_id=18#
2. RxFiles
3. Schulman, S., & Crowther, M. A. (2012). How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood, 119(13), 3016-3023. Accessed February 27, 2017. https://doi.org/10.1182/blood-2011-10-378950.
4. Lexi-drugs

Feb. 24, 2017We have a patient who started Lantus 3 weeks ago and has had nasal congestion since. Is there any information available on that effect? Will it resolve on it's own? details
 

Medical Problems: no other medical problems disclosed
Medication History: Lantus insulin
Response: Sinusitis and rhinitis are relatively common adverse events associated with Lantus; sinusitis occuring in ~3-18% and rhinitis occuring in ~3-6% of patients. (1, 2, 4, 5). These side effects may go away with time as the product is being used. (4) Recommmend continuing on with Lantus as the side effects may become resolved or reduced over time. If the symptoms are moderately bothersome the patient could try a saline nasal spray or an intranasal corticosteroid. (3)
References: 1. SIDER- Lantus
2. Lexidrugs- Lantus
3. M. Varghese, M. C. Glaum and R. F. Lockey, Clinical & Experimental Allergy, 2010 (40) 381–384
4. https://www.drugs.com/sfx/lantus-side-effects.html#refs
5. Lantus product monograph (Sanofi-Aventis)

Feb. 27, 2017When will the drug Dupilumab be available? It is used for "itchy, scratchy skin" (urticaria?) details
 

Response: Dupilumab does not have a notice of compliance yet. (1) Sanofi hopes to get FDA approval around the end of March 2017.
In two phase 3 trials it showed a reduction of 2 or more points from baseline and a score of 0 or 1 (clear or almost clear) in approx 37% of dupilumab compared to the 10% who received placebo in atopic dermatitis. The studies were over 16 weeks therefore longer term efficacy studies are required(2).
References: 1. Health Canada Notice of Compliance
2. http://www.nejm.org/doi/full/10.1056/NEJMoa1610020
3. http://www.pmlive.com/pharma_news/sanofi_eyes_march_approval_for_dupilumab_in_atopic_dermatitis_1144809

Feb. 27, 2017Can you use an oral DHEA as an alternative to topical DHEA 0.5% for the purpose of vaginal dryness? details
 

Patient Age: 45
Patient Sex: F
Medical Problems: hx breast cancer (currently in remission)
vasomotor symptoms + vaginal dryness (menopausal)
Mental health (depression + anxiety)
insomnia
osteoporosis
Medication History: gabapentin 900mg daily ( hot flashes)
sertraline 100mg qhs( depression + anxiety)
tamoxifen 20mg qam
topical DHEA 0.5% 1.3 mms daily (vaginal dryness)
Response: DHEA cream (applied vaginally or to the thigh) and intravaginal suppositories have shown to be effective in treating vaginal atrophy in post menopausal woman. (1) DHEA is the precursor of sex steroids and supposedly acts on local tissues to convert precursors into estrogens and androgens. (2)DHEA has been taken safely by mouth for 12-24 month, a DHEA 1-10% cream up to 12 months, and inside the vagina for 12 weeks. DHEA is possibly unsafe when used orally for long term at higher doses; long term use of 50 to 100 mg of DHEA daily can produce higher DHEA serum levels and potentially puts them at risk for cancer including breast cancer. (1)
It is reported that oral DHEA supplements may stimulate growth of mammary cancer cells in presence of low level estrogen. (3) This may be due to a DHEA metabolite directly affecting mammary cells, indirectly increasing estrogen levels, or through an increased concentration of free-insulin like growth factor that may stimulate oestrogen receptors. (3) Studies have reported a positive correlation between higher serum concentrations of DHEA and increased breast cancer risk in postmenopausal woman (but not premenopausal women). (3) Vaginal localized DHEA has minimal to none changes in serum steroids as patients have remained within normal post menopausal ranges. (4) It is not suggested to use vaginal estrogen therapy or vaginal DHEA in patients on aromatase inhibitors with breast cancer, however low dose use in breast cancer patients with a low risk of recurrence may be reasonable and should be determined by the patient’s oncologist. (4)
References: 1. Natural Medicine Database- DHEA
2. Sage Journals: treatment of vaginal atrophy- http://journals.sagepub.com/doi/full/10.2217/WHE.14.9
3. http://www.nature.com/ejcn/journal/v53/n10/abs/1600889a.html
4. UptoDate

Feb. 27, 2017How long does it take for antihypertensives to have a full effect? Specifically amlodipine. Patient is on multiple blood pressure medications and we are wondering when we should try to increase their dose of amlodipine 5 mg po BID? details
 

Medical Problems: BP > 160/90 sometimes up to 200/90
Medication History: Hydrochlorthiazide 12.5 mg - increasing 25 mg (feb 28th)
Candesartan 32 mg
Metoprolol 50 mg po BID
Amlodipine 5 mg po BID
Response: Amlodipine steady state is usually reached within 7-8 days of consecutive daily dosing. (3 ) BP response should be evaluated 2 to 4 weeks after initiating or making changes in therapy. (2). Amlodipine will have significant reductions in BP at 24-48 hours after first dose. (1)
References: 1. http://accesspharmacy.mhmedical.com/drugs.aspx?GbosID=133634#monoNumber=133634§ionID=153409904&tab=tab0
2. Depiro Pharmacotherapy textbook - hypertension
3. Drug product database- amlodipine accel pharma

Feb. 28, 2017An MD has prescribed Albendazole 400mg OD x 1 wk for what they think is cutaneous larva migrans (the patient has recently returned from a trip to Jamaica). This medication is only available through SAP so is there some other medication that can be used? details
 

Patient Sex: F
Medical Problems: ?cutaneous larva migrans (CLM)
Medication History: no info available
Response: The drugs of choice are Ivermectin and albendazole (ivermectin preferred). (1,2,3) Both are only available through SAP. Dose of ivermectin: 12mg or 200mcg/kg po x 1 dose. (1,2,3) No other available treatments are recommended. In fact, there is a Canadian article which addressed the fact that CLM "treatment in Canada is only available through the Special Access Program (SAP) of Health Canada, thus, many patients are prescribed ineffective courses of non-targeted therapy" and the importance of using the first line treatments: ivermectin and albendazole. (2)
References: 1. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 115661, Cutaneous larva migrans; [updated 2015 Nov 01, cited 2017 Feb 28]; Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=115661&site=dynamed-live&scope=site. Registration and login required.
2. Kincaid L, Klowak M, Klowak S, Boggild AK. Management of imported cutaneous larva migrans: A case series and mini-review. Travel Med Infect Dis. 2015 Sep-Oct;13(5):382-7 PMID: 26243366
3. Helmut Albrecht, M.D., Carlos Franco-Paredes, M.D., MPH. Cutaneous Larva Migrans. Antimicrobe: Infectious Disease & Antimicrobial Agents. http://www.antimicrobe.org/b08.asp#t7

Mar. 1, 2017What is the long term safety of tranexamic acid? Patient had fibroids removed and has had 5 courses of it to date. details
 

Medical Problems: fibroids removed
Medication History: Tranexamic Acid
Response: Information is available from one observational study looking at long-term effects of tranexamic acid being used cyclically for menorrhagia. This study included 723 women who were followed for 27 cycles of 1.3 g TID for up to 5 days per cycle. The discontinuation rate was 69.5%, the reason being adverse in 17.8%.
Specific adverse events reported:
- severe blurred vision occurred in one patient which resulted in discontinuation from the study
- nausea was one of the most frequently reported treatment-emergent gastrointestinal adverse events occurring in 14.4% (104/723) of patients
- the mean decrease in platelet count from baseline to study termination was -13,233 (from 298,791 to 282,689)
- a case of severe allergic reaction (dyspnea, throat tightening, and facial flushing) that required emergency medical treatment was reported in a patient on her fourth treatment cycle
- arthralgia occurred in 14.5% (105/723) of patients
- back pain occurred in 31.4% (227/723) of patients
- migraine occurred in 10.8% (78/723) of patients (1)
References: 1. DrugDex
2. Ophthalmological examination of patients in long-term treatment with tranexamic acid. Theil PL. Acta Ophthalmol (Copenh). 1981 Apr;59(2):237-41. PMID: 7257742

Mar. 1, 2017UTIs are a common SE of Invokana. How are they usually managed? Patient was put on chronic MacroBID daily. details
 

Medical Problems: diabetes (T2DM)
Medication History: Invokana
MacroBID
Response: Patients on long-term treatment of MacroBID for 6 months or longer are at increase risk of developing chronic pulmonary reactions, including diffuse intersistial pneumonitits, pulmonary fibrosis or fatalities. Pulmonary fibrosis has most frequently occurred in post menopausal woman and most cases have been reversible following discontinuation of MacroBID and beginning steroid therapy. (1) The most serious chronic effects involve the pulmonary and hematologic systems, as well as various peripheral neuropathies. (2) Neuropathy has occurred in elderly, renal dysfunction or chronic use of macrobid patients. (2)
References: 1. Micromedex- Macrobid
2. Toxnet - Macrobid

Mar. 1, 2017I am giving a presentation on pre-exposure prophylaxis (PrEP). How much does a month of PrEP cost? Does a GP prescribe it? details
 

Response: Truvada is currently the only drug indicated for PrEP in Canada.(5) The cost of this drug is ~$850/30 day supply. The drug is not covered on the Saskatchewan formulary for this indication so all Saskatchewan formulary patients would pay out of pocket. Some third party insurers are covering on a case-by-case basis but maximums and deductibles may result in incomplete coverage.(6) It appears NIHB patients are covered for this drug as there are no restrictions to its indication.
The GP can prescribe. However, prescription of PrEP should include a comprehensive prevention strategy as well as routine follow-up (every 3 months) to monitor HIV status, adverse effects, and re-inforce prevention strategy.(2,5) If a GP is not comfortable with this, they can refer patients to Infectious Disease physicians (this is the case in Saskatoon.)(6)
References: 1. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf
2. RxTx - Truvada
3. NIHB
4. PharmaClik
5. http://www.catie.ca/en/fact-sheets/prevention/pre-exposure-prophylaxis-prep
6. Phone communication with Pharmacist, Positive Living Saskatoon, 655-0688

Mar. 1, 2017Patient is on Dexilant and finding it expensive. What is a PPI that is as effective and less expensive? details
 

Medical Problems: Likely dyspepsia (patient said there is no actual diagnosis)
Response: All of the PPIs are of equal equivalence(1); none are superior so cost and formulation are the major decision factors. Patient has no third party insurance and is covered by the Saskatchewan formulary (SDPEBB). The SDPEBB has recently implemented a MAC policy for PPIs: pantoprazole and rabeprazole are covered under this policy.(2) All other PPIs will be more expensive by virtue of their higher cost/dose and that the SDPEBB will only cover up to the cost of rabeprazole or pantoprazole.(2) Suggested to switch to pantoprazole or rabeprazole.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-GI-EvidencePearls.pdf
2. http://formulary.drugplan.ehealthsask.ca/News.aspx

Mar. 1, 2017Our patient is on a fentanyl 25 mcg patch. We tried to reduce her to the 12 mcg patch but she is having intolerable "crawling skin feeling". She experiences sweats and shakes and says that she can tolerate that but the skin crawling feeling is not tolerable. Are there any options for this? We were considering adding on clonidine for withdrawal but the patient is concerned with this as she tends to have low BP. She has not tried anything else in the meantime. details
 

Medication History: Taking buproprion x 150mg OD
Temazepam 30 mg HS
Response: Clonidine may reduce physical symptoms of withdrawal. To ensure it will be tolerated a test dose of 0.1 mg can be given with HR and BP being checked 1 hr after the dose administration. If BP < 90/60, postural hypotension or HR < 60 it shouldn’t be further prescribed. (3)
Methadone and buprenorphine have shown to be superior over clonidine in treatment of supervised withdrawal as two meta-analysis showed patients were more likely to complete treatment and reduce withdrawal symptoms. (1) Baclofen has also been used in opioid withdrawal. (2)
References: 1. Uptodate
2. Dynamed: opioid abuse or dependence
3. Rx files- slow opioid taper
4.RxTx: drug withdrawal syndromes

Mar. 1, 2017Ondansetron 4-8mg BID is given to chemotherapy cancer patients for a couple days following treatment to prevent nausea. There is often a drug interaction showing up if the patient is on other agents that prolong the QTc interval. Is this a concern when the patient is on a low dose on Ondansetron for a couple days? All I have found is it would be an issue with IV Ondansetron. details
 

Response: Ondansetron prolongs QT interval in a dose dependent manner, especially in doses greater than 32 mg IV. (1, 3) Arrythmias, torsades de pointes, atrial fibrillation and other cardiac dysfunction have been reported during post marketing use of ondansetron IV injection although causation has not been confirmed. (4) In a RCT cross-over trial with healthy patients, researchers found a maximum mean difference in QTc interval of 19.5 milliseconds with a single dose 32 mg IV ondansetron which was significantly higher than the mean QTc max of 5.6 msec with 8 mg IV ondansetron (doses were infused over 15 minutes). (4). Risk of dose dependent QT prolongation is expected to be greater with faster and larger IV infusions of ondansetron. (6) The initial IV dose of ondansetron in patients > 75 years old must not exceed 8 mg and patients < 75 years old must not exceed 16 mg IV. (6) Infusions should be no less than 15 minutes. (6) Oral ondansetron is approximately 85% bioavailable in cancer patients and approximately 50-70% bioavailable non cancer patients due to first pass metabolism. (10) There however have been no recommended changes for oral dosing. (6)

Be aware of common QT prolongation drugs including quinolones, macrolides, and antipsychotics. (8) If patient has multiple risk factors (female, elderly, electrolyte disturbances, cardiac dysfunction etc.) for QT prolongation or is on combination of medications known to cause QT prolongation a baseline ECG may be warranted. (1) A good website specifically for QT prolongation and TdP risk with medications commonly prescribed for cancer patients is Credible Meds for Healthcare Professionals OncoSupport Drug List. (9) In conclusion, it seems ondansetron high dose IV has the most risk for QT prolongation. Suspect that occasional low dose oral ondansetron would have less/minimal significant QT prolongation (Rx files threshold < 10 msec) however patient factors and medications may contribute to increased QT prolongation and patient should be assessed appropriately. (1)
References: 1. Downey, S. Jensen, B. Reiger, L.QT prolongation and torsades de pointes: drugs and sudden death. 10th ed. Saskatoon, SK: Saskatoon Health Region. [updated 10 Oct 2014; accessed 02 March 2017]. Available from: http://www.RxFiles.ca
2. Credible meds
3. SIDER
4. Micromedex
5.FDA https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm310219.htm
6. Health Canada http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/39943a-eng.php?_ga=1.67850004.406906479.1452788418

Mar. 1, 2017A patient undergoes PD dialysis QID. Cephalexin 500 mg QID has been prescribed. The dose adjustment for hemodialysis is 250 mg every 12-24 hrs with supplemental dose 250 post dialysis. Does PD dialysis remove as much as hemodialysis? Is this dose too much? details
 

Response: The manufacturer does not provide dosing adjustment for cephalexin however some clinicians follow the guidelines 250 to 500 mg every 12 to 24 hrs. (1) Patients with PD should receive the same dose as those with renal failure. (2)
References: 1. Lexidrugs

Mar. 2, 2017We have an ALS patient using Atropine Drops. His sister is asking if they can harden the saliva. Apparently he is coughing a lot now - a choking type of cough and they feel it is because his secretions are too thick. details
 

Patient Sex: M
Medical Problems: ALS
Medication History: Scopolamine patch
Atropine Drops SL qid
Response: ALS patients do have problems with thickening secretions for 3 reasons:
1) drying of secretions with medications such as the Atropine and scopolamine
2) low airflow as a person’s breathing capacity declines
3) loss of diaphragm muscle strength which diminishes the ability to cough. (1)
Guaifenesin is a recommended treatment: 400mg po every four hours. (1,2) Other medications that can help break up thick secretions are nebulized salbutamol, Combivent or Mucomyst used up to QID on a regular basis. (2)
References: 1. Secretion Management in ALS @ http://www.alsphiladelphia.org/document.doc?id=1983&frsid=5848
2. Catherine Lomen-Hoerth. Amyotrophic Lateral Sclerosis from Bench to Bedside Semin Neurol. 2008;28(2):205-211. @ http://www.medscape.com/viewarticle/572273_6

Mar. 2, 2017I work at the LTC facility in Duck Lake. I'm sure that Versed can be used SC in palliative patients, but our local pharmacy says it can't. What can you tell me? details
 

Response: Subcutaneous administration of Versed is an off-label use, however, it is often used this way in palliative care. (1,2,3) I'm including a link to a SHR document listing meds that can be used SC in palliative care. (1) If you need more information, please let us know.
References: 1. https://www.saskatoonhealthregion.ca/about/NursingManual/1074.pdf
2. Masman AD1,2,3, van Dijk M4,5, Tibboel D4,5, Baar FP4,6, Mathôt RA. Medication use during end-of-life care in a palliative care centre. Int J Clin Pharm. 2015 Oct;37(5):767-75.
3. Nathan Cherny. Palliative sedation. In: UpToDate, Arnold, RM (Ed),UpToDate, Waltham, MA. (Accessed on March 2, 2017.)UpToDate, Waltham, MA. (Accessed on November 25, 2013.)

Mar. 2, 2017Is there any information about an association between PPI use and glaucoma? details
 

Patient Age: 57
Patient Sex: F
Medical Problems: Glaucoma diagnosed Oct 16
Medication History: Pantoprazole 40 mg daily started in Feb 16
Response: Drugs which are known to cause or exacerbate glaucoma include corticosteroids, antimuscarinic drugs (antihistamines, antidepressants, antispasmodics), and topiramate. (2). Pantoprazole is known to cause visual disturbance in less than 1% of patients. (1) In post marketing surveillance there have been reports of ischemic optic neuropathy and blurred vision. In another study treating patients with Zollinger-Ellison syndrome or hypersecretory conditions, 4 of 34 patients experiencd visual disturbances including blurry vision and eye floaters, appearing or worsening during pantoprazole use. (1) Spontaneous and slow resolution over six months was reported. (1) I did not find anything specifically that pantoprazole can contribute to or cause glaucoma however it does appear to cause eye disturbances in very few patients.
References: 1. Micromedex- Pantoprazole
2. Rxtx - glaucoma
3. Rxfiles- glaucoma

Mar. 3, 2017We have received a prescription for Demerol 50mg 1-2 tabs qid prn. The patient is 72 years old. Is this appropriate? Is dosing too high? details
 

Patient Age: 72
Patient Sex: F
Medical Problems: Not known
Medication History: Not known
Response: Demerol should not be used for the treatment of acute pain unless other opioids are contraindicated or unavailable, especially if pain is expected to last > 3 hours. It's metabolite,- normeperidine, is neurotoxic and its accumulation can cause seizures or other CNS side effects such as tremors and hallucinations. Due to slower rate of metabolism in elderly and hepatic or renal impairment, use is not recommended in this population. (1,2)
The dosage seems fine. 50 to 150 mg every 3 to 4 hours as needed is recommended. (3)
References: 1. RxTx [Internet}. Ottawa (ON): Canadian Pharmacists Association; 2017. Bailey, B. Acute Pain; [updated August 2016; cited 03 March 2017]. Available from:https://www.e-therapeutics.ca/.
2. Mariano ER. Management of acute perioperative pain. In: UpToDate, Fishman S (Ed), UpToDate, Waltham, MA. (Accessed on March 3, 2017.)
3. Lexicomp Online

Mar. 3, 2017Can Forxiga be given with insulin - in this case - Lantus and Humalog? details
 

Medical Problems: T2DM
Medication History: Lantus
Humalog
Response: Yes, if blood glucose is not well-controlled with the insulin combination. The dosage of the insulins should be decreased on initiation of the Forxiga because of the possibility of hypoglycemia (1,2) and adjusted as needed. (1,2)
References: 1. David K McCulloch. Management of persistent hyperglycemia in type 2 diabetes mellitus in UpToDate
2. Lexicomp interactions

Mar. 6, 2017Is there any new information on the benefits of Lodalis? We are seeing more prescriptions for it. Any real evidence? I have someone with previous MI with stenting who is currently on ezetimibe only and cannot tolerate statins. Please reply to all details
 

Medication History: ezetimibe
Response: Lodalis (colesevelam) is a bile acid sequestrant used to lower cholesterol. It is indicated for use in those who cannot tolerate a statin or in addition to regular/reduced dosed statins. It works by preventing reabsorption of bile acids. Once bile acids are depleted, the hepatic enzyme cholesterol hydroxylase is increased which further converts cholesterol to bile acids. This in turn increases demand for cholesterol in liver and increases clearance of LDL from the blood. (2)

Lodalis is more potent than other bile acid resins (so smaller doses are appropriate), has fewer GI effects, and less influence on absorption of other drugs. (2) Some commonly reported side effects include constipation, dyspepsia, and nausea. (2) Lodalis will lower total cholesterol about 7-10%, LDL 15-18% and increase HDL about 3%. (2) It can increase triglycerides about 10% so it should be avoided in patients whom TG > 3.4 mmol/L. (2) It may reduce the absorption of ezetimibe. Therefore ezetimibe should be given two hours before or 4 hours after Lodalis. (3) I did not find evidence for Lodalis and associated CV risk reduction unlike statins.
References: 1. DynamedColesevelam
2. Pharmacists letter PL Detail-Document, New Drug: Lodalis (Colesevelam). Pharmacist’s Letter/Prescriber’s Letter. May 2012.
3. Lexi-drugs Colesevelam
4. Uptodate lipid lowering with drugs other than statins and fibrates

Mar. 6, 2017A patient is on a second round H. pylori treatment (the doctor wants to do second round for insurance of efficacy). Patient could not do original Hp-PAC. Is Pepto Bismol (bismuth subsalicylate) compatible with Pradaxa therapy? It was presumed the stomach bleed was caused by H. pylori so a blood test was redone and found to be positive. Pepto was not taken during the first course of therapy (thought it was only used for as needed therapy). Are there other options for treating H pylori in penicillin allergic patients? What is the Pepto there for? details
 

Medical Problems: Pencillin allergy
Medication History: Prevacid, bismuth subsalicylate, tetracycline, metronidazole
Pepto Bismol (bismuth subsalicylate) - 2 tabs QID for 14 days
Pradaxa 150 BID- second month filled today (was on warfarin for prevention of clots and then got a clot)
Response: No major drug interaction between Pepto Bismol and dabigatran. Each of these agents possess the potential to cause bleeding. Their combined use would seem to increase that potential. Recommended monitoring for increased signs of bleeding.
Increase monitoring diligence for signs and symptoms of bleeding if these agents are used concomitantly. (1, 2)
First line therapy for H pylori infections in penicillin allergic patients includes: Pepto Bismol, PPI, metronidazole and tetracycline. (3) An alternative therapy in pencillin allergic patients includes pantoprazole + clarithromycin + metronidazole. (3) Bismuth subsalicylate may exhibit antisecretory, antimicrobial, and anti-inflammatory effect. (5) Serology cannot be used to determine cure from infections (antibodies still detectable 6-12 months after eradication). (4)
References: 1. Lexidrug interaction checker
2. Stockleys drug interaction checker
3. Bugs and Drugs
4. Rxfiles h pylori testing and eradication
5. Lexidrugs- bismuth subsalicyclate

Mar. 6, 2017A 15 year old male (67 kg) with severe nodular acne (non responsive) was initiated on Accutane. He was tolerating 20 mg BID for 1 month well and then was increased 30 mg BID (1 month). Since the increase he's experienced a severe skin reaction (arms red, chapped breaking down, from wrist down, bilateral)- no other rashes on his arms. Front of neck is diffusely bright red, sharp demarcated line on the front (not extending to the back of the neck) - essentially where cold air come into contact with skin. The rash appeared about a week into his new dose. Skin is bright red and there is some dryness and chapping/chafing. He has been putting sunscreen on those areas. Is it safe to reduce to the dose of his accutane or should I discontinue it? details
 

Patient Age: 15
Patient Sex: M
Medication History: concerta
Response: Post marketing reports of severe skin reactions associated with Accutane, like Stevens-Johnson syndrome, toxic epidermal necrolysis, and erthema have been reported. A Roche global safety database (as of 2009) reported 66 incidences of severe skin reactions in adults and children worldwide, however there are approximately 16 million medication users. (2) Stevens-Johnson is generally associated with a fever, painful rash with lesions or vesicles and bullae, and can influence oral, ocular, and genital mucosa regions. (1) I agree the rash you described sounds like a photosensitivity as the redness is localized to exposed skin whereas more severe reactions tend to occur on various parts of the body and the rash is only presenting as redness. To manage the photosensitivity you can trial a decreased dose of Accutane or apply hydrocortisone cream to a small area to see if it helps reduce the redness and itchiness. (4)
References: 1. Uptodate
2. Health Canada- http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2010/14064a-eng.php
3. Micromedex- isotretinoin
4. http://emedicine.medscape.com/article/1049648-treatment

Mar. 6, 2017A patient was prescribed Metoclopramide for gastroparesis BEFORE starting Ralivia and Wellbutrin. She is wondering if she can start her metoclopramide again as her symptoms have returned. I'm getting mixed results on the severity of the interaction between Ralivia(tramadol) and metoclopramide. What is the mechanism behind this interaction? details
 

Patient Age: 45
Patient Sex: F
Medical Problems: Gastroparesis
Pain
Medication History: Cortef
Wellbutrin
Ralivia 100-200 mg OD
Metoclopramide
Response: Tramadol and metoclopramide may have drug interactions varying from increased sedation to increased seizures and serotonin syndrome. (2, 5) The risk of serotonin syndrome is potentially due to tramadol’s active metabolites binding to μ-opiate receptors in the CNS and inhibition of reuptake of norepinephrine and serotonin. (1)
High doses of metoclopramide block dopamine and serotonin receptors in the CNS and it is not recommended in addition to drugs with potential for extrapyramidal side effects due to increased seizure risk. (2)
Additionally, tramadol (CYP2D6 substrate) concentrations may be increased when given with CYP2D6 inhibitors such as bupropion. Tramadol’s opioid activity is due to conversion of metabolite whereas the parent compound has serotonergic activity. Therefore, reduced tramadol metabolism may further increase serotonergic activity with decreased opioid effect. (2, 4,7)
Overall, patient preference and risks vs benefits should be considered before restarting metoclopramide.
References: 1. Lexi-drugs tramadol
2. stockleys drug interaction checker
3. Lexi interaction checker
4. Lexi-drugs buproprion
5. Micromedex- tramadol and bupropion
6. Lexidrugs metoclopramide
7. RxTx- opioids

Mar. 6, 2017I have a 2 month old who vomits after every feeding. Is ranitidine the DOC? details
 

Patient Age: 0
Patient Sex: M
Medical Problems: 2 month old vomits after feeding
Response: Acid suppressing medications have a limited role in the treatment of infants with regurgitation. They are not valuable in treating children less than one year of age with uncomplicated GER ("happy spitters").
When pharmacotherapy is chosen as a treatment, or for a limited trial, a PPI is generally preferred over histamine type 2 receptor antagonists (H2RA). (1)
Gastroesophageal reflux: Limited data available: Corrected age <44 weeks: Oral: 2 mg/kg/dose every 8 hours (2)
References: 1)UTD - Gastroesophageal reflux in infants
2)Lexicomp - (Birch, 2009; Sutphen, 1989, Wheatley, 2012)

Mar. 7, 2017Does amlodipine interact with grapefruit juice? I've always told patients it did but now I'm looking on Lexicomp, Pharmacists Letter and eCPS and I am not finding any information. details
 

Response: There are some interactions with grapefruit juice and calcium channel blockers however none were recognized with amlodipine. (1,3,4) The sensitivity of the reaction with grapefruit juice may be related to the calcium channel blocker bioavailability. (1) Amlodipine has high bioavailability and is minimally affected by grapefruit juice whereas lower bioavailable CCBs such as felodipine are significantly affected by grapefruit juice. (1) The influence of grapefruit juice on bioavailablity of amlodipine seems to be neligible and not clinically significant. (1)
References: 1. Stockleys drug interaction checker
2. Pharmacists letter
3. Micromedex
4. Food and Drug interactions book

Mar. 7, 2017A patient is allergic to fentanyl patch (redness / welts on patch site). They have tried hydroxyzine and rotating patch sites. Are steroid creams or other dosage forms (e.g. Flovent spray) a possibility? details
 

Response: Topical steroids may be used in treating mild-moderate contact dermatitis.(1) Systemic steroids also provide relief within 12-24 hrs and are used if severe or widespread contact dermatitis occurs.(1) Trying another brand may be beneficial for the patient as the different brands have different adhesives. If skin irritation occurs with fentanyl patches, steroidal sprays have been used; wait 1 minute after spraying before applying the new patch.(2) There is minimal evidence for the steroid spray with allergic dermatitis and the sprays can be rather expensive if the patient has no coverage. However they can be used as a last resort.
References: 1. Dynamed
2. Rxfiles- opioid analgesics

Mar. 7, 2017Could Invokana lead to elevated oxalates in the urine? Is there a list of medications causing elevated oxalates in the urine or information on what causes elevated oxalates? details
 

Response: It appears as if there are three conditions that can cause high oxalate content in urine or hyperoxaluria; an inherited genetic disorder, eating too many oxalate rich foods, and/or intestinal diseases that increase absorption of dietary oxalates such as gastric bypass, Crohn’s disease, short bowel syndrome or other malabsorption issues. With a genetic disorder the liver doesn’t create or produce enough enzyme to prevent over-production of oxalate (likely not influenced greatly by diet). In disorders with excess absorption via diet or intestinal disorder it may be more important to reduce oxalate content in diet. (3) Foods known to be high in oxalate content include rhubarb, spinach, potatoes, legumes and nuts (1) Patient may also require a low-fat diet. (1) It also appears that high dose vitamin C may increase absorption of oxalate. (1) If there is excess absorption of oxalate then calcium carbonate or cholestyramine may be used to reduce absorption. (1) Patient should undergo testing to determine if they have a genetic disorder or excessive absorption causing high oxalate content in the urine. (2) I did not find information regarding Invokana increasing urine oxalate levels.

An association of oxalates and vulval pain was found involving a woman with vulvodynia. She presented with high levels of oxalate in her urine. Her symptoms resolved and oxalate levels declined after starting a low-oxalate diet and calcium citrate to remove oxalate from the body. In the US, a low oxalate diet is widely used for treatment of vulvodynia. (4)
References: 1. Up to date- prevention of recurrent calcium stones in adults
2. Uptodate – primary hyperoxaluria
3. Ohf.org – oxalosis and hyperoxaluria foundation
4. Vulval pain society- http://www.vulvalpainsociety.org/vps/index.php/treatments/the-low-oxalate-diet

Mar. 7, 2017Are there any drug interactions with azithromycin and this patient's medications? details
 

Medication History: Alprazolam
Cyclobenzaprine
Ranitidine
Response: No interactions identified (2).
References: 1. Lexi-drug interaction checker
2. Stockleys drug interaction checker

Mar. 7, 2017A patient is just starting Invega Sustenna and his mother would like to know in advance how one discontinues it. (There have been some bad experiences.) details
 

Response: Potential consequences of abrupt discontinuation (or large dose reduction) of an antipsychotic include discontinuation syndrome (flu-like), psychosis, and movement disorders.(1) However, because plasma concentrations of depot antipsychotics gradually decline, there is less concern of discontinuation syndrome and movement.(1) Certainly return of underyling condition is still a concern if not replaced by another antipsychotic.
References: 1. Clinical Handbook of Psychotropic Drugs, 20th Ed, pg 110

Mar. 10, 2017What schedule is Synvisc? details
 

Response: Synvisc (hyaluronic acid in concentrations of 5% or more) is Schedule II.(1,2) The hyaluronic acid products for which concentrations are available (Euflexxa, Durolane, Monovisc, Neovisc, Synvisc, Synvisc-One) are <5% (3-5) and, therefore, unscheduled.
References: 1. NAPRA National Drug Schedule
2. http://scp.in1touch.org/uploaded/web/refmanual/Administrative_Bylaws_CURRENT.pdf
3. RxTx
4. Lexicomp
5. http://www.durolane.com/img/document/DUROLANE_Science_of_the_single_injection.pdf

Mar. 10, 2017A patient is currently on Butrans patches and is switching to medical marijuana? How do I go about this? details
 

Response: There is no equivalent dose of opioids and marijuana. Tapering of high dose opioid can be considered before starting marijuana as there may potentially be additional CNS depression with the combination. (4)
A taper may be considered to reduce withdrawal symptoms if receiving a higher dose buprenorphine patch, however withdrawal is generally mild and resolves in 2 weeks. (2) You may want to begin by reducing the patch every 10 days to the lowest dose tolerated. (2) Additionally, there is an estimated dose equivalency for the patch and other opioids on RxFiles Q and A: Butrans Patch for Weekly Application for converting opioids to Butrans patches which may be of some assistance.
Levels of the drug usually decline 50% after removal of the patch after approximately 12 hrs. (2) Administration of other opioids should be delayed at least 24 hrs after removal of patch. (2)
The initial usual dose of smoked marijuana is 65-195 mg. (5) The Health Canada website is a useful resource for further information about medical marijuana.(6) If the patient is in the process of seeking medical marijuana, do not begin the taper until it is approved because approval may take some time.
References: 1. Health Canada drug product database- buprenorphine
2. RxFiles: BuTrans Patch Buprenorphine Transdermal System (BTDS) for Weekly Application
3. http://www.helpmegetoffdrugs.com/taper#form
4. Pharmacists Letter- Medicinal Marijuana
5. Rxfiles: Cannabindoids
6. http://www.hc-sc.gc.ca/dhp-mps/marihuana/med/index-eng.php

Mar. 10, 2017How significant is the interaction between mycophenolate and PPI? Can they just monitor the levels and adjust the dose as needed? details
 

Medical Problems: indications unknown
Response: Proton pump inhibitors (PPIs) may decrease serum mycophenolate acid levels, depending on the product used.(1,2) Several studies have suggested significant reductions (17-37%) in the active metabolite, mycophenolic acid (MPA), when PPIs have been combined with mycophenolate mofetil (MMF).(2) However, other studies have shown no significant difference in MPA levels with MMF and PPI use.(2) The clinical significance and apparent interaction is unclear so caution is warranted with the combination.(2)
It appears as if the enteric coated mycophenolate sodium tablets (EC-MPS) are less sensitive to the PPI interaction and it may be an alternative to patients needing a PPI.(1,2) Most studies reported no significant change in MPA levels with enteric coated mycophenolate sodium and PPI.(2)
Those receiving higher doses of PPIs may be at increased risk of lower MPA levels.(2) Data suggests pantoprazole may not affect mycophenolate and one study suggested low dose rabeprazole didn’t affect mycophenolate concentrations.(1) Serum/plasma monitoring is not undertaken for MMF (3) so monitoring takes the form of observation of clinical response. If the MMF is being used post organ transplant, one may want to consider avoiding PPIs or using EC-MPS.
References: 1. Stockleys Drug Interactions
2. Lexicomp Drug Interaction Checker
3. eCPS

Mar. 10, 2017A patient has been on amantadine 100 mg TID with food. It is shorted. What can we do? details
 

Patient Age: 78
Patient Sex: M
Medication History: Levodopa/carbidopa CR and regular
Trihexyphenidyl 2 mg TID
Quetiapine 12.5 mg TID
Response: Referred to Amantadine shortages document.(1)
References: 1. http://medsask.usask.ca/documents/drug-shortages/Amantadine%20Hydrochloride.pdf

Mar. 10, 2017How frequent/severe is cross-sensitivity reaction with nortriptyline and carbamazepine (prescribed yesterday for TMJ)? The patient had a rash with nortriptyline and there is very little/weak information about the cross sensitivity with CBZ. He is NOT of Asian descent but is of Lebanese heritage (is a landed immigrant). Not sure if the cross sensitivity is a factor in developing the fatal skin reaction. Can you weigh in? details
 

Patient Age: 54
Patient Sex: M
Medical Problems: Chronic Pain
TMJ
HTN
Migraine (unsure if with/without aura)
Allergies: Nortriptyline : RASH Note: tolerating Amitriptyline
Medication History: Nabilone, Amitriptyline, Hydromorph contin, Botox injections (for migraines)
**Carbamazepine 100mg (chew) BID ** (new not dispensed)
Metoprolol
Response: It is true that TCAs and carbamazepine (CBZ) share similar structures. CBZ has been associated with serious skin reactions including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS).(3) Furthermore, there are five reported cases of patients who experienced a hypersensitivity reaction to a TCA after a prior reaction to CBZ.(2)
However, only if your patient’s reaction to nortriptyline involved more than rash (i.e. systemic effects such as chills, fever) or was severe would complete avoidance of CBZ be warranted. The fact your patient is tolerating amitriptyline is reassuring. I think it’s important the patient be educated to immediately report any dermatological reactions but there appears to be no reason to avoid CBZ altogether.
References: 1. Lexicomp Aromatic Anticonvulsant Allergy/Hypersensitivity (Drug Allergy and Idiosyncratic Reactions)
2. Seitz CS, Pfeuffer P, Raith P, et al. Anticonvulsant hypersensitivity syndrome: cross-reactivity with tricyclic antidepressant agents. Ann Allergy Asthma Immunol. 2006 Nov;97(5):698-702. PMID 17165282
3. DrugDex

Mar. 10, 2017Patient has been treated for parasites in the intestine with Vermox, then Combantrin; both failed. MD has prescribed Humatin but the family can't afford it. Are there any other agents that could be used? details
 

Patient Age: 8
Patient Sex: M
Medical Problems: Intestinal parasite - dientamoeba fragilis, blastocytis hominis
Medication History: Tried Vermox and Combantrin
Response: Metronidazole 50 mg/kg/day PO divided TID x 10 days is the most suitable alternative.(1) It is effective for blastocystis hominis and is an alternative for dientamoeba fragilis.(1) The preferred treatments for dientamoeba fragilis are iodoquinol, which is no longer available(2) and paromomycin, which was prescribed but is not affordable.
References: 1. Bugs and Drugs app
2. DPD

Mar. 10, 2017Do I need to document the sale of Olex like I do for Tylenol #1? details
 

Response: Schedule II means a pharmacist needs to be involved in discussion with the patient.(1) There is no legislation for omeprazole compelling pharmacies to document sales, whereas this is the case with Tylenol #1.(2)
References: 1. http://scp.in1touch.org/uploaded/web/refmanual/Regulatory_Bylaws_Current.pdf
2. http://scp.in1touch.org/uploaded/web/refmanual/Exempted_Codeine_Products_20140610.pdf

Mar. 10, 2017How should I manage the Dostinex drug shortage? What are some alternative therapies? details
 

Response: Shortage is estmated to be resolved April 6th. Please see medSask Drug Shortages cabergoline PDF on how to manage cabergoline shortages.
References: 1. http://www.drugshortages.ca/searchresult.asp
2, http://www.medsask.usask.ca/documents/drug-shortages/Cabergoline.pdf
3. Pharmaclic - Cabergoline

Mar. 10, 2017Dose prednisone decrease ASA levels? Is this of concern for someone taking low-dose ASA? Should the ASA dose be increased? details
 

Response: Serum salicylate levels are reduced by steroids; however the main concern is following steroid withdrawal in those taking moderate to high doses of ASA.(1) The discontinuation of the steroid may result in increased ASA levels (has been associated with a 3 to 9 fold increase) and symptoms of toxicity.(2) As low-dose ASA is not expected to interact,(1) no dose adjustment is required.
References: 1. Stockleys Drug interactions
2. Lexidrugs interaction checker

Mar. 13, 2017A patient was prescribed Zofran orally dissolving tablet but the regular tablet was dispensed. What is the difference? It says they have the same bioavailability, but do the dissolving tablets work faster? details
 

Response: There is no difference in terms of bioavailability or onset of action between the two products.(1,2) The ODT tablets are placed on the tongue and swallowed after disintegration; as such, they are also absorbed orally.(3) The ODT tablets may be advantageous for those who have trouble swallowing tablets, or for those who are too nauseous to drink liquid/swallow a tablet or capsule.(3)
References: 1. Micromedex- Ondansetron
2. Lexidrugs - Ondansetron
3. Canadian Pharmacist's Letter 2013; 20(11):291130

Mar. 14, 2017Is melatonin safe in breastfeeding? (The infant is 6 days old.) details
 

Response: There is minimal data for melatonin supplementation during breastfeeding and effects are relatively unknown.(1,2) Melatonin is naturally excreted in the breastmilk and infants have been safely given melatonin directly in doses higher than what would be expected from breastmilk.(2) That said, due to the limited information regarding the safety of melatonin supplmentation in breastmilk and that the infant is a neonate some recommend against its use.(1)
References: 1. Briggs in Pregnancy and Lactation
2. LactMed

Mar. 14, 2017My patient has an LDL 0.3, HDL 0.7, with a history of MI and is taking atorvastatin 40 mg once daily (recent increase from 20mg daily). Is there any evidence for statin therapy in low LDL patients? What is considered "too low"? Is there a benefit or is therapy still indicated if cholesterol levels are very low? details
 

Patient Age: 68
Patient Sex: M
Medical Problems: Previous MI
Heart failure
(No history of diabetes or hypertension)
Response: The common guidelines for statin therapy, such as that of the American College of Cardiology do not mention how to manage low LDL, but some articles have explored targeting lower LDLs to assess if there is a greater benefit with more aggressive treatment.
This patient would have been put on a statin following the heart attack, as this would be considered clinical atherosclerotic cardiovascular disease. (2) One of the four benefit groups according to the American College of Cardiology is patients with atherosclerotic disease; and it is recommended to put them on moderate to high intensity statin. (1) According to UpToDate, the existing data does not support any specific recommendations for patients that happen to present with an initial LDL baseline below 1.29 mmol/L, but they suggest that if therapy seems to be warranted, a low dose of statin is acceptable. (5)
Once statin therapy is initiated, however, there is not a lot of information on handling very low LDL levels; most studies look at “low” LDL (likely higher than 0.3mmol/L) or explore theoretical implications of very low LDL levels. According to the atherosclerotic Cardiovascular disease Primary Prevention Guidelines, it is not recommended to lower statin therapy in response to low LDL levels, saying “Expert opinion is that no LDL level is too low.” (11) With respect to there being benefit of continued therapy, DynaMed reported that all levels of cholesterol that are treated with statin therapy show a decrease in mortality and CV events, though the actual LDL numbers in that range were not disclosed. (2) Though there may not be mention of levels as low as 0.3mmol/L, some studies have mentioned that patients with conditions that create very low LDL levels (hypobetalipoproteinemia) with LDL below 1.86mmol/L have a lower risk of CV disease, as well as those on statin therapy with LDL below 1.7 mmol/L had a greater reduction in the occurrence of cardiovascular events. (10,12) The PROVE-IT trial found that a more aggressive target (<1.86mmol/L) showed a 16% relative risk reduction of primary composite endpoint that included all-cause mortality, MI, unstable angina requiring hospitalization, requiring a PCI or CABG, and stroke. (9) LDL <1.6 mmol/L was also shown to improve survival. (4)
As far as the risks associated with having a low LDL, statin patients with LDLs below 0.8mmol/L to 1.07mmol/L had side effect frequency comparable to those that had higher LDL levels on statin therapy, (6,12) with a slight increase in myopathy and risk of developing diabetes. (12) In studies that looked at the newer non-statin drug for lowering cholesterol (alirocumab), patients with LDL as low as 0.4mmol/L to 0.67mmol/L did not have a higher frequency of side effects, apart from a slight increase in risk of cataracts. (7) Low LDL is sometimes believed to be a risk for cognitive impairment. A systematic review of RCTs of statin therapy found no association between being treated with statins and cognitive decline; the LDL numbers of the study were not disclosed but it did include participants on higher intensity statin therapy. (3) Critical capacities of steroid hormone and bile acid production are preserved, and the cholesterol blood-brain barrier continues to protect cells of the central nervous system even at extremely low LDL-C levels. (13)
Bottom line is that therapy is likely still beneficial for secondary prevention in a post MI patient with low LDL levels, but it may be up to clinical judgement to determine the most appropriate dose to use for treatment.
References: 1. Micromedex
2. DynaMed
3. Ott B, Daiello L, Dahabreh I, Springate B, Bixby K, Murali M et al. Do Statins Impair Cognition? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of General Internal Medicine. 2015;30(3):348-358.
4. Leeper N, Ardehali R, deGoma E, Heidenreich P. Statin Use in Patients With Extremely Low Low-Density Lipoprotein Levels Is Associated With Improved Survival. Circulation. 2007;116(6):613-618.
5. UpToDate
6. Wiviott S, Cannon C, Morrow D, Ray K, Pfeffer M, Braunwald E. Can Low-Density Lipoprotein Be Too Low? The Safety and Efficacy of Achieving Very Low Low-Density Lipoprotein With Intensive Statin Therapy. Journal of the American College of Cardiology. 2005;46(8):1411-1416.
7. Robinson J, Rosenson R, Farnier M, Chaudhari U, Sasiela W, Merlet L et al. Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab. Journal of the American College of Cardiology. 2017;69(5):471-482.
8. Healthline
9. PROVE-IT: Atorvastatin 80 mg reduces major CV events by 16% compared with pravastatin 40 mg in ACS patients
10. John C. LaRosa, MDa, , , Scott M. Grundy, MD, PhDb, John J.P. Kastelein, MDc, John B. Kostis, MDd, Heiner Greten, MDe. Treating to New Targets (TNT) Steering Committee and InvestigatorsSafety and Efficacy of Atorvastatin-Induced Very Low-Density Lipoprotein Cholesterol Levels in Patients With Coronary Heart Disease (a Post Hoc Analysis of the Treating to New Targets [TNT] Study). The American Journal of Cardiology. 2017;100(5):747–752.
11. Cohen A. © 1996 Kaiser Foundation Health Plan of Washington. All rights reserved. 1 Atherosclerotic Cardiovascular Disease (ASCVD) Primary Prevention Guideline [Internet]. Kaiser Permanente. 2016 [cited 14 March 2017]. Available from: https://www.ghc.org/static/pdf/public/guidelines/ascvd-primary.pdf
12. Kostis W. How Low an LDL-C Should We Go With Statin Therapy?. Current Atherosclerosis Reports. 2014;16(2).
13. Olsson A, Angelin B, Assmann G, Binder C, Björkhem I, Cedazo-Minguez A et al. Can LDL cholesterol be too low? Possible risks of extremely low levels. Journal of Internal Medicine. 2017.

Mar. 14, 2017What are the treatment options for eosinophilic esophagitis? A patient was prescribed an Advair MDI but told to swallow the treatment; would a nasal spray be better? Are allergy shots warranted? The patient's allergy specialist told her it would be beneficial but to research it herself. details
 

Medical Problems: eosinophillic esophagitis (EoE)
Medication History: Advair, PPI- using for esophagitis (but not effective)
PO prednisone in the past
Response: Treatment of eosinophilic esophagitis (EoE) consists of:
1. Acid Suppression with PPIs- PPIs may be beneficial for EoE by reducing acid production in patients with co-existent GERD or through other anti-inflammatory mechanisms. As the esophagus may be inflamed, PPIs will confer protection to potential acid exposure. Approximately 1/3 of patients have good results with PPI alone. In a randomized study patients received esomeprazole 40 mg for 8 weeks along with swallowed fluticasone; treated patients experienced significant improvement in symptoms of dysphagia regardless of GERD status.(1) These may not be appropriate if the patient is not finding any benefit from the PPI.
2.Topical glucocorticoids: Most patients receive swallowed fluticasone which is administered using an MDI without a spacer. The medication is sprayed into the mouth and swallowed; the patient should not eat or drink for 30 minutes after administration. Adults should use 500 mcg twice daily. If treatment is not beneficial, the dose may need to be increased or the patient can be switched to oral viscous budesonide (budesonide nebules mixed with sucralose [4]). Budesonide can also be administered using a nebulizer and having the patient swallow the accumulated liquid. Patients generally continue with treatment for 8 weeks and if relapse is an issue afterwards a maintenance dose or dietary changes may be considered. (1)
Desensitization with purified known allergen could be effective in controlling EoE. It may reduce the burden of allergy and risk of anaphylaxis however there is the possibility that the immunotherapy may trigger the EoE (as seen in mice). Further research is needed to determine safety and efficacy. (2)
Other potential therapies for EoE include systemic steroids (especially if patient has severe disease) and esophageal dilation. Esophageal dilation will relieve dysphagia but not improve the underlying inflammation. (1)
References: 1. Uptodate: Treatment of Eosinophilic Esophagitis
2.Doughtery T, Stephen S, Borum M, Doman D. Emerging Therapeutic Options for Eosinophilic Esophagitis. Gastroenterology & Hepatology Volume 10, Issue 2 [published Feb 2014, cited March 2017]. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011375/
3. Uptodate: Management of benign esophageal strictures
4. Dohil R, Newbury R, Fox L, et al. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology. 2010 Aug;139(2):418-29.

Mar. 14, 2017What do you know about a short chain fatty acid enema for use in diversion colitis? details
 

Medical Problems: Not available
Medication History: Not available
Response: Diversion colitis is characterized by inflammation of the defunctionalized, bypassed colon following surgery. Most patients with diversion colitis are asymptomatic, but in a small proportion of patients, symptoms can significantly impact quality of life.(1) Diversion of the colon results in deficiency of short-chain fatty acids (SCFA) along with other nutrients. Bacterial metabolism results in SCFA synthesis. SCFA are absorbed by the lumen which then supplies fuel to mucosal cells, modulates fluids and electrolytes, enhances colonic motility and mucosal blood flow, and production of inflammatory cytokines. (1) SCFA enemas may be used as initial therapy for diversion colitis in those unable to undergo surgery. They may be used in IBD along with ASA and glucocorticoids. The enemas must be compounded and consist of sodium acetate (60 mmol), sodium propionate (30 mmol), and sodium n-butyrate (40 mmol) with additional sodium chloride (22 mmol). This yields a similar osmolality to plasma and pH is adjusted to 7.0 with sodium hydroxide. The enema is instilled twice daily for 6 weeks at a dose of 60 mls. Frequency may be reduced if improvement occurs. (1)
Sodium butryrate instillation has been shown to increase colonic mucin synthesis. (2) Further studies need to be done to determine the relationship between the mucous layer and diversion colitis. (2)
Results for SCFA enemas have been conflicting. In one randomized crossover trial of 10 patients with IBD and colectomy, SCFA enema use for 3 weeks was not shown to improve inflammation compared to placebo. However these patients had severe inflammation which may have been due to IBD. (1) Another study of 8 patients received SCFA and had significant increased proliferation of rectal mucosa compared to placebo. (3)
References: 1. Uptodate- Diversion Colitis
2. Kabir S, Kabir S, Richards R, Ahmed J, MacFie J. Pathophysiology, clinical presentation and management of diversion colitis: A review of current literature. International Journal of Surgery. [accessed March 14, 2017]. Available from: http://www.sciencedirect.com/science/article/pii/S1743919114008346
3. Mortensen F, Langkilde N, Jorgenson J, Hessov I. Short chain fatty acids stimulate mucosal cell proliferation in the closed human rectum after Hartmann’s procedure. International Journal of Colorectal Disease [published August 1999, accessed March 14, 2017]. Available from: http://link.springer.com/article/10.1007%2Fs003840050201

Mar. 14, 2017Is there an interaction between carbamazepine and vaginal estrogen cream? If so, what is the mechanism? details
 

Medical Problems: indication for carbamazepine unknown
dry vaginal symptoms
Medication History: amitriptyline, Premarin vaginal cream
Response: Carbamazepine is an enzyme inducer that may increase estrogen metabolism, thereby reducing its effectiveness; however, this is not relevant for locally applied estrogen used for menopausal vaginits.(1) The combination has no effect on carbamazepine levels. (1,2)
References: 1. Stockleys Drug Interaction Checker
2. Lexicomp Drug Interaction Checker: carbamazepine, estrogens (conjugated, equine) systemic

Mar. 15, 2017Is Aclasta interchangeable with the generic? details
 

Medication History: Taro no stock, Aclasta
Teva - d/c
Dr. Reddy's - inventory
Response: Taro and Teva (5mg /100 ml) generics are available and approved for osteoporosis treatment but they aren't available right now. (1,2) There is a Dr. Reddy's zoledronic acid 5mg/100ml product available however is it only indicated for prevention of postmenopausal osteoporosis in women with osteopenia and Paget's disease.(1,2) More concentrated generics are available but they are indicated only for bone metastases . (1) We don't know why the Aclasta is the only version covered by EDS.
References: 1. eCPS
2. DPD
3. NOC database
4. http://www.gov.pe.ca/photos/original/PIDL.pdf
5. http://formulary.drugplan.ehealthsask.ca/PDFs/PREFACE_Updated_March_1_2017.pdf

Mar. 15, 2017With the discontinuation of dehydrated alcohol injection, we are looking for alternative treatments for methanol/ethylene glycol poisonings. We carry Fomepizole in one of our hospitals, but have not stocked it in all locations due to cost implications. - How quickly after ingestion does antidote therapy need to be instituted (ie: would we have time to transport a patient to another facility?) -What alternative therapies have good evidence? Is oral alcohol a good option- if so, looking for dosing parameters/protocols for both adult & pediatric patients details
 

Response: How quickly after ingestion does antidote therapy need to be instituted (ie: would we have time to transport a patient to another facility?)
- Other than the general recommendation of “begin treatment ASAP for better outcomes” (1,2), there was one study that specifically looked at the timing of providing the antidote and how it impacted outcomes (3). They found that delaying the antidote more than 6 hours increased rates of death OR prolonged renal insufficiency and associated morbidity significantly (composite end-point, odds ratio of 3.34). They do not conclude that giving the antidote within 6 hours is optimal (it could be within 1-2 hours, for example), but delaying more than 6 hours definitely leads to more harm. The optimal time to begin treatment is “as soon as possible.”

What alternative therapies have good evidence? Is oral alcohol a good option? If so, what are the dosing parameters/protocols for both adult & pediatric patients?
- Other than Fomepizole and intravenous ethanol, oral ethanol is the only other antidte; hemodialysis is the best treatment in the setting of severely poisoned treatments.(2)
o Note that oral dosing of ethanol is considered inferior to fomepizole or IV ethanol because (2):
-difficult to dose, and maintain appropriate levels -> necessitates frequent testing and infusion adjustments.
-higher likelihood of side effects
-lower cost, but increased monitoring makes it similar, or possibly worse, in terms of cost effectiveness compared to fomepizole (4). This is not definitive, however: a study from Europe (5) found using IV-ethanol was significantly more cost-effective than fomepizole in 96 poisonings. This World Health Organization suggests fomepizole is likely more cost-effective depending on regional costs of acquisition and staffing (6).
Oral ethanol dosing protocols suggested (for both pediatric and adult):
- Distilled spirits (40 to 50 percent vol/vol) intended for human consumption can be diluted to a 20 percent solution, and administered orally or via nasogastric tub, at a loading dose of 5 mL/kg of a 20 percent solution to raise ethanol serum concentrations by 1000 mg/L (22 mmol/L), and 0.5 mL/kg per hour for the initial maintenance dose.

O Another protocol (1) (basically the same, slightly lower dose):
- Oral ethanol may be used as a temporizing measure until intravenous ethanol or fomepizole can be obtained, but it is more difficult to achieve the desired stable ethanol concentration. The loading dose is 0.8 grams/kg (4 mL/kg of 20% {40 proof}) ethanol diluted in juice administered orally or via a nasogastric tube. Maintenance dose is 80 to 150 mg/kg/hour (of 20% {40 proof}) ethanol; 0.4 to 0.7 mL/kg/hour for a non-drinker; 0.8 mL/kg/hour for a chronic alcoholic). Concentrations greater than 30% (60 proof) ethanol should be diluted. For both modalities, blood ethanol levels must be monitored hourly and adjusted accordingly, and both require patient monitoring in an ICU setting.
References: 1. Micromedex, Toxdex: Treatment of ethylene glycol poisonings
2. UpToDate, treatment of ethylene glycol poisoning
3. https://www.ncbi.nlm.nih.gov/pubmed/24371252 - J Intensive Care Med. 2015 Jul;30(5):270-7. doi: 10.1177/0885066613516594. Epub 2013 Dec 26. Predictors of Death and Prolonged Renal Insufficiency in Ethylene Glycol Poisoning.
4. https://hero.epa.gov/hero/index.cfm/reference/details/reference_id/1230439
5. http://www.jccjournal.org/article/S0883-9441(17)30334-9/fulltext?rss=yes
6. http://www.who.int/selection_medicines/committees/expert/19/applications/Fomepizole_4_2_AC_Ad.pdf

Mar. 16, 2017At what rate do you suggest titrating Lipitor? Can you start at 10 mg and double the dose every 7 days to 80 mg? details
 

Medical Problems: Hx MI
high TG
high Framingham
Medication History: Statin-naïve, no interacting meds
Response: There is no indication to titrate statin doses.(1-4) Start with the required dose (in this case 80 mg); reduce if not tolerated.(4)
References: 1. http://www.cfp.ca/content/61/10/857.full
2. eCPS - Lipitor
3. RxTx - Post-myocardial Infarction
4. http://www.rxfiles.ca/rxfiles/uploads/documents/Lipid-Statin-Intolerance.pdf

Mar. 16, 2017What are alternate topical treatments for molloscum contagiosum? I usually use imiquimod but it's very expensive and often not covered. I thought I saw something about potassium hydroxide but I don't know how that would be used? details
 

Response: Treatments for molluscum in immunocompetent children with the most evidence include:
-No treatment(1,2)
-Curettage(1,2)
-Cantharidin(1,2)
-Podophyllotoxin(2) (children 10 years and older)
Treatments with limited evidence of benefit include potassium hydroxide, salicylic gel, tretinoin cream, and several others.(1,2)

Cantharidin is available from pharmacies as the brand name Canthacur®. It is applied with the blunt end of cotton swab to lesion only in the office. Application is painless and does not cause bleeding. The area can be washed with soap and water within 2-6 hours. The agent causes small blisters at the lesion site. If lesions persist, treatment can be repeated in 2-4 weeks.(1)

Podophyllotoxin 0.5% solution is the active ingredient of podophyllin, an antimitotic agent; pharmacies can order the brand Condyline®. This solution can be applied at home once or twice daily 3–4 days per week for up to 4–6 weeks. Pain, burning, erosions, pruritus and bleeding may occur. If applied to large areas (>10 cm2) or in high concentrations, systemic absorption may result in neurotoxic effects, limiting use.(4)

The only information availabel for the application of potassium hydroxide comes from the only RCT that wasn’t terribly helpful. In the methods it described(4):
"The parents or caretakers were given verbal and written instructions outlining how to apply the solution to each lesion twice daily with a cotton swab until the lesions showed signs of inflammation. Treatment was to be discontinued if inflammation occurred."
References: 1. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 -2017. Record No. 116448, Molluscum contagiosum; [updated 2015 Aug 20, cited 16 Mar 2017]; [about 15 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=116448&site=dynamed-live&scope=site. Registration and login required.
2. UTD - Molluscum contagiosum
3. Short K, Fuller C, Higgins M. Double-Blind, Randomized, Placebo-Controlled Trial of the Use of Topical 10% Potassium Hydroxide Solution in the Treatment of Molluscum Contagiosum. Pediatr Dermatol 2006 May-Jun;23(3):279
4. CTMA - Viral Skin Infections: Common and Flat Warts

Mar. 16, 2017Can melatonin be used for sleep in an individual who is 17 weeks pregnant? details
 

Patient Sex: F
Response: Melatonin: No Human Data—Animal Data Suggest Moderate Risk. (3) Melatonin doses very near the human dose based on body weight did adversely affect the development of the neuroendocrine reproductive axis in female rat fetuses. There is probably no relationship of this toxicity in pregnant humans consuming occasional low (≤10 mg) doses, but high doses or frequent use during gestation should be avoided. (3)
Schaefer has these recommendations:
▪ For sleep disorders requiring medication, sedating antihistamines, trazodone, amitriptyline, and, if necessary benzodiazepines or zolpidem are recommended
▪ Benzodiazepines are the drugs of choice for the brief treatment of acute symptoms and, in certain cases, sleep disturbances during pregnancy
▪ For sleep disorders requiring continuous medication, the antidepressants trazodone or amitriptyline are preferable.
(1)
References: References :
1. Schaefer, C., Wisner, K. Drugs During Pregnancy and Lactation Third Edition, 2.11, 293-339
2. UpToDate - Teratogenicity, pregnancy complications, and postnatal risks of antipsychotics, benzodiazepines, lithium, and electroconvulsive therapy. Accessed on-line 08Sep2016
3. Briggs, Gerald G.; Freeman, Roger K.; Yaffe, Sumner J., Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th Edition

Mar. 17, 2017A woman in her early 60's who has never had chicken pox is wondering about getting Zostavax. Will it be harmful? Should she get chicken pox vaccine instead? details
 

Response: As per Canadian Immunization Guidelines, Canadians 50 years of age and older with no known history of varicella infection are still eligible for herpes zoster vaccination. Patients should not obtain lab confirmation - there are no known safety concerns of herpes zoster vaccine in healthy patients susceptible to varicella virus. Only if lab confirmation of varicella virus has been obtained in the past for other reasons would one vaccinate with two doses of univalent varicella vaccine. (1)
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html

Mar. 31, 2017A 92 year old patient is not taking anything orally. Can amoxcillin capsules be administered rectally? Or would a compounded suppository work? details
 

Patient Age: 92
Patient Sex: F
Medical Problems: audible crackles, SOB - pneumonia?
Response: The only information available is from an abstract in which ampicillin rectal suppository was compared to amoxicillin suspension administered rectally. While the abstract provides information about plasma concentrations for ampicillin, but not amoxicillin, 86% in the amoxicillin group (n=229) achieved cure plus clinical improvement compared to 89% of the ampicillin group (n=454). There was less perianal irritation in the amoxicillin group (5.2%) than the ampicillin group (12.1%).(1)
Amoxicillin may be sufficiently absorbed when administered rectally.
References: 1. J Int Med Res. 1988 Sep-Oct;16(5):376-85. Clinical evaluation of rectally administered ampicillin in acute otitis media. Bergström BK1, Bertilson SO, Movin G. - access to abstract only.
*Pubmed, Alt ROA resources

Mar. 31, 2017What can be done about the phosphate tablet shortage? details
 

Response: There are liquid sodium phosphate solutions (marketed for laxative use) and contain 4.14 mmol phosphorus and 4.8 mmol sodium per ml (9,10), such that ~4ml is ~ 1 Phosphate-Novartis tablet. The products available at McKesson are Phoslax by Odan (NPN 80000689 ) and Phosphates Solution by PMS (NPN 02230399).(7). Note: while the Phosphate-Novartis tablets have been discontinued(11), a similar product by JAMP is said to be available the end of April.(7)
Also, dietary intake can be increased. Dieticians of Canada phosphorus content of foods available.(14)
References: 1. UpToDate - Evaluation and treatment of hypophosphatemia
2. eCPS (Supplied section all that available)
3. Martindale
4. CTMA Constipation
5. https://www.medicines.org.uk/emc/medicine/25270
6. LNHPD
7. PharmaClik
8. http://sunnybrook.ca/uploads/PTBull36_Phosphate_IV.pdf
9. Phone communication with Christine, Odan Customer Service, 1-800-387-9342, Mar 31, 2017
10. http://www.globalrph.com/phosphate_supplements.htm
11. Phone communication with , Novartis Customer Service, 1-800-465-2244, Mar 31, 2017
12. DPD
13. http://pendopharm.com/product/phosphates-solution/
14. https://www.dietitians.ca/Downloads/Factsheets/Food-Sources-of-Phosphorus.aspx

Mar. 31, 2017I have a patient on Hydroxyurea 500 mg BID (I now reduced it to 500mg od). This to reduce her essential thrombocythemia. Problem is her K+ keeps going above 5.0. She is now on Lasix 40 mg BID just to reduce her K+; there is no other indication for it. I have been able to keep her K+ to 4.8 but now her platelets are slowly rising - now at 682 because of the lower hydroxyurea dose for the last week. Any suggestions as to how to proceed with this case especially keeping her K+ down?? details
 

Patient Age: 68
Patient Sex: F
Medical Problems: Platelets usually 580
highest was 5.5 last week, ECG not conducted
BP good and not dehydrated (drinks plenty of fluids)
atrial fibrillation
no thromboembolism
Medication History: metoprolol, amiodarone, warfarin, ranitidine 150 mg BID, ferrous gluconate, bupropion 150 mg XL, clondine 0.05 mg BID
Response: I found but one case report of hydroxyurea (HU)-associated hyperkalemia in a patient with polycythemia vera.(2) Unfortunately, it’s a typical case report with few details. While the authors describe normalization of potassium levels with discontinuation of the HU, they do not provide any information about how the condition was subsequently managed.
There have been three cases reported via MedEffect(3); however, all of these seem to be tumour lysis syndrome as other metabolic abnormalities (hyperuricemia, hyperphosphatemia, hypocalcemia) were present, which is typical of tumour lysis syndrome.(4) This patient has no other lab abnormalities.
No reason to believe any of the other drugs would be a causative factor, whether by interaction or adverse effect profile was found.(11-13)
Pseudohyperkalemia. There is a decent amount of information regarding pseudohyperkalemia in patients with myeloproliferative disorders.(15-18) In these reports, pseudohyperkalemia was defined as a difference of ≥0.4 mmol/L between serum and plasma concentrations.(16,17) Generally, some blood cells leak potassium that causes a false increase in serum samples, but not plasma samples.(16) If this were the case, the patient's potassium levels would be expected to increase with reduced dose of HU (because her platelets increased) but in fact her potassium levels decreased. Because it is possible furosemide was affecting potassium simultaneously, if simultaneous plasma and serum samples can be ordered, pseudohyperkalemia can easily be ruled in or out.
Should this be a true hyperkalemia,low dose Kayexalate (sodium polystyrene sulfonate – SPS) is reasonable to try. One case series describes use of 15 g once daily (required lowering in some patients) who were experiencing hyperkalemia due to ACEI/ARB therapy.(19) The SPS was added to be able to maintain the ACEI/ARBs. They followed these patients for a mean 14 months; baseline potassium was 6.4 mmol/L which was reduced to 4.6 mmol/L (time span is not noted so close monitoring at the beginning will be important). Some did experience nausea but this subsided with continued use. It is best to use the sorbitol-free product(19), which is powder.(21)
Dietitians of Canada have a good resource of how to maintain a low potassium diet, which includes potassium content of foods without labels (e.g. fruits/vegetables)(20)
Finally, the US has a couple of new products for hyperkalemia that seem to be better tolerated than SPS.(14) One that seemed most appropriate for chronic use is patiromer.(14) This agent isn’t available in Canada. I did contact the Special Access Programme on the off-chance it’s available through them. I haven’t heard back from them and I really do not expect it to be on the program.
References: 1. http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Hydroxyurea_monograph_1Oct2013.pdf
2. Hyperkalaemia associated with hydroxyurea in a patient with polycythaemia vera. Marusic S, Gojo-Tomic N, Bacic-Vrca V, Bozikov V. Eur J Clin Pharmacol. 2011 Jul;67(7):757-8. doi: 10.1007/s00228-010-0962-7. Epub 2010 Dec 14. No abstract available. PMID: 21153897
3. MedEffect Adverse Drug reaction database
4. UTD - Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors
5. UTD - Prognosis and treatment of essential thrombocythemia
6. Buemi M., Fazio M.R., Bolignano D., et al. Renal complications in oncohematologic patients. J Invest Med 2009; 57(8):892-901
7. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf
8. DPD
9. NOC database
10. UTD - Treatment and prevention of hyperkalemia in adults
11. DrugDex
12. Stockley's
13. Lexicomp
14. Core Evid. 2017 Mar 23;12:11-24. doi: 10.2147/CE.S129555. eCollection 2017. Clinical utility of patiromer, sodium zirconium cyclosilicate, and sodium polystyrene sulfonate for the treatment of hyperkalemia: an evidence-based review. Beccari MV1, Meaney CJ1
15. Pseudohyperkalemia in patients with increased cellular components of blood. Sevastos N, Theodossiades G, Savvas SP, Tsilidis K, Efstathiou S, Archimandritis AJ. Am J Med Sci. 2006 Jan;331(1):17-21. PMID: 16415658
16. When is a high potassium not a high potassium? Teh MM, Zaman MJ, Brooks AP, Li Voon Chong JS. J R Soc Med. 2003 Jul;96(7):354-5. No abstract available. PMID: 12835454
17. Pseudohyperkalemia occurring in a patient with chronic renal failure and polycythemia vera without severe leukocytosis or thrombocytosis. Fukasawa H, Furuya R, Kato A, Yonemura K, Fujigaki Y, Yamamoto T, Hishida A. Clin Nephrol. 2002 Dec;58(6):451-4. PMID: 12508968
18. Unexplained hyperkalemia: The tip of the iceberg. Meka NP, Malik YO. Am J Case Rep. 2012;13:125-7. doi: 10.12659/AJCR.883151. Epub 2012 Jun 22. PMID: 23569507
19. Secondary prevention of hyperkalemia with sodium polystyrene sulfonate in cardiac and kidney patients on renin-angiotensin-aldosterone system inhibition therapy. Chernin G, Gal-Oz A, Ben-Assa E, Schwartz IF, Weinstein T, Schwartz D, Silverberg DS. Clin Cardiol. 2012 Jan;35(1):32-6. doi: 10.1002/clc.20987. Epub 2011 Nov 6. PMID: 22057933
20. https://www.healthstandnutrition.com/wp-content/uploads/2011/09/Low-K-diet.pdf
21. eCPS
*Pharmacists letter (drug-induced hyperkalemia)

Mar. 31, 2017How long after receiving Zostavax do you need to wait before taking prednisone? Dose is for prednisone 10 mg PO OD x 10 days then 5 mg PO OD for 2 months. details
 

Response: The threshold dose of prednisone considered sufficient to interfere with immune response such that Zostavax should not be given (or prednisone started after Zostavax) is 20 mg once daily.(1) Since this patient's dose does not exceed 10 mg, there is no concern.
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html

Mar. 31, 2017Can breastfeeding be continued when using topical fluorouracil? Any considerations? details
 

Medical Problems: 18 month old infant
some sort of sun spot about the size of the tip of one's pinkie finger
Response: There is no need to discontinue breastfeeding if using topical fluorouracil on small areas.(1,2) Contact of the infant's skin to the treated area needs to be avoided.(1)
References: 1. Lactmed
2. Hale - Medications and Mothers' Milk

Mar. 31, 2017Does clonidine need tapering? details
 

Patient Age: 54
Patient Sex: F
Medical Problems: vasomotor symptoms
Medication History: clonidine 0.1 mg OD x 4-5 days then 0.2 mg x 3 days (only was on total 7-8 days)
asked caller and no beta-blocker on board
Response: Clonidine can cause some withdrawal symptoms such as agitation, insomnia, nervousness/anxiety, flushing, nausea, sweating, tachycardia, and tremor if discontinued abruptly.(1,2) The risk increases with: use over 1-2 months, concomitant beta-blocker use, hypertension, cardiovascular disease, daily dose >=1.2 mg.(1) In such cases, a taper of 25% every 2-7 days has been recommended.(1,2)
This patient has only been on the drug for a week and is on a low dose; therefore, tapering is not necessary. That said, if she has some 0.1 mg tablets at home, there is no harm in going to those for a few days before final discontinuation.
References: 1. Geri RxFiles, pg 177
2. Clincial Handbookd of Psychotropic Drugs for Children and Adolescents, 3rd ed. pg 39

Mar. 31, 2017Are there any contraindications, precautions, disease, or drug interactions to be aware of when considering use of evolocumab and adalimumab? Patient is young and high CV risk with uncontrolled LDL on crestor and ezetrol, and cardiologist wants to start evolocumab. Patient is receiving adalimumab for unknown indication. details
 

Response: No drug interactions between evolocumab and adalimumab were identified.(1-4) According to a recent review, "A possible mechanism of interaction with these combinations [two or more monoclonal antibodies] would involve the FcRn-mediated recycling. However, given the total amount of endogenous IgG of 50–100 g, the usual dose of most mAbs of <10 mg/kg is not predicted to affect the total IgG plasma concentration and thus the “salvage pathway” is not affected by the risk of saturation process."(5)
The possibility of additive immunosupppression was considered; however while adalimumab does cause immunosuppression,(4) the target of evolocumab, PCSK9, is not involved in the immune system and there is no indication evolocumab affects the immune system.(3,6)
As such there is no reason to believe any interaction exists between adalimumab and evolocumab.
References: 1. Stockley's
2. Lexicomp
3. eCPS - Repatha
4. ECPS - Humira
5. Pharmacol Res. 2016 Sep;111:592-9. doi: 10.1016/j.phrs.2016.07.015. Epub 2016 Jul 18. Pharmacokinetics interactions of monoclonal antibodies. Ferri N, Bellosta S, Baldessin L, et al.
6. http://www.tandfonline.com/doi/full/10.1080/21678707.2016.1189323?src=recsys
*Pubmed: evolocumab immunosuppression

Apr. 1, 2017How long can a risperidal consta be left out of the fridge? details
 

Response: The Risperdal Consta Kit should be stored under refrigeration, however, if there is no refrigeration available, it can be stored at room temperature (<25 degress C) for 7 days. Once the product is reconsituted it should be used immediately, however it is stable for 6 hours.
References: 1. Risperdal Consta Drug Product Monograph

Apr. 3, 2017I have permethrin 5% prescribed for a 4 month old but my references say not to use in under 2 year. What to use for scabies in 4 month? details
 

Response: Permethrin 5% can be used on infants greater than 2 months, though it is off label use. The hairline, neck, temples, and forehead may be infested in infants and geriatric patients. In these populations, permethrin should also be applied to the scalp and face, sparing the eyes and mouth.
References: 1. UpToDate, treatment of scabies

Apr. 3, 2017Is it ok to crush Onglyza? details
 

Response: The tablets are film-coated(1) and immediate release.(3) While the monograph says not to split or cut, this is due to the absence of kinetic data of altered tablets.(3) This drug does not appear on the Do Not Crush list(2) and the manufacturer was unable to provide any reasons (such as taste/mucosal irritation) to avoid crushing.(2) As such, crushing is reasonable so long as they are crushed immediately prior to administration.
References: 1. eCPS
2. http://www.ismp.org/tools/donotcrush.pdf
3. Phone communication with AST medical information, (question originally emailed to: questions@ASKmedical.ca), Apr 4, 2017
*Alt Route Admin

Apr. 3, 2017I want to treat a 5 year old with rogaine 5%. She has alopecia areata. Any evidence for safety or efficacy? details
 

Patient Age: 5
Patient Sex: F
Medical Problems: alopecia areata
Medication History: failed diprosone cream
Response: Rare cases of hypertrichosis have been associated with topically applied minoxidil.
There is a reported case in the Brazilian literature of generalized hypertrichosis affecting a 5-year-old child, following use of minoxidil 5%, 20 drops a day, for hair loss. The laboratory investigation excluded hyperandrogenism and thyroid dysfunction. Topical minoxidil should be used with caution in children. (An Bras Dermatol. 2016 Jan-Feb;91(1):87-8.)

Hypertrichosis is a common side effect of topical minoxidil treatment in women. Although usually localized to the face, it may occasionally involve limbs and other body areas.

Systemic absorption of the drug is typically minimal with topical therapy, with 1.4% of the applied dose being absorbed. However, hypotheses on the pathogenesis of the diffuse hypertrichosis reaction routinely include systemic absorption, as well as high sensitivity of the follicular apparatus to minoxidil.

In the case of a 2 year old, the excessive dose (both in terms of concentration and daily quantity) in combination with the patient’s low body weight favoured systemic adsorption. Further support for systemic effects are noted in the reported cardiovascular side affects in three patients from 10 to 14 years of age treated for alopecia areata with minoxidil 2% topically twice a day 8. These effects included sinus tachycardia, sensation of palpitation and dizziness.

The efficacy of topical minoxidil in alopecia areata has never been definitively proven. The possibility of systemic absorption contraindicates, in some reasearchers opinion, this treatment in young children, who can develop serious cutaneous or systemic side effects. ( F1000Res. 2013 Oct 28;2:226. doi: 10.12688/f1000research.2-226.v1. eCollection 2013.)
References: 1. PMID: 26982785
An Bras Dermatol. 2016 Jan-Feb;91(1):87-8. doi: 10.1590/abd1806-4841.20164010.
Infantile generalized hypertrichosis caused by topical minoxidil.
2.PMID: 24555107
F1000Res. 2013 Oct 28;2:226. doi: 10.12688/f1000research.2-226.v1. eCollection 2013.
Minoxidil induced hypertrichosis in a 2 year-old child.

Apr. 3, 2017Can a person have the Zostavax injection on the same day they had Prolia? Person is 69 years old. details
 

Medication History: aventyl 25, synthroid 50mcg, zolmitriptan 2.5mg, prolia a few months ago
Response: There are no drug interactions or contraindications for getting zostavax after having the prolia injection.

Unlike other live vaccines, because HZ vaccine is not used for eliciting a primary immune response, it is reasonable to consider HZ vaccine in people receiving low dose immunosuppressive therapy.

Prolia is used with caution in patients with impaired immune systems or using concomitant immunosuppressive therapy; may be at increased risk for serious infections.
References: 1. Pharmacist Letter
2. Micromedex
3. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html
4. lexicomp

Apr. 3, 201715 yo anemic patient taking 35 mg elemental iron tid. He is intolerant to this, is there an injectable version? details
 

Patient Age: 15
Patient Sex: MALE
Medical Problems: 15 yo with anemia
Medication History: 35 mg elemental iron tid
Response: Has patient tried taking iron with a meal to decrease GI side effects? (Will decrease absorption, but may have meal/snack high in vitamin C to slightly increase absorption- will still be decreased overall though)
Yes, a parenteral version is available. Dexiron 50 mg/ml (2 ml vial) is available for IV administration.
IM generally not recommended as it is painful, stains the buttocks, and has variable absorption and case reports of sarcoma (1)
IV Dexiron is the cheapest and most convenient form of IV Iron. Dexiron and Venofer not available for another couple of weeks. Dexiron and the other option Venofer are not available from the manufacturer for at least a few weeks.
Dose for Dexiron:
Iron-deficiency anemia: IV Dexiron
Dose (mL) = 0.0442 (desired hemoglobin - observed hemoglobin) x LBW + (0.26 x LBW)
Desired hemoglobin: Usually 14.8 g/dL
LBW = Lean body weight in kg
This is to be diluted in NS before administering via IV
Max= 1-1.5g/dose
***Initial test dose needed (Sensitivity test)- Administer slow IV >5min of 0.5 mL (25 mg iron), observe >1 hour for sensitivity rxn before giving the remainder. (3)
References: 1- UptoDate
2- Lexicomp Dexiron
3- RxFiles –Iron Management

Apr. 3, 2017Have you ever heard of using patenolol eye drops in the nostrils? I have an Rx for it and wonder if this is an acceptable way to administer the drops? details
 

Patient Age: 13
Patient Sex: M
Medication History: nasonex, reactin
Response: Olopatadine comes in a nasal spray called Patanase 0.6%. It is used for seasonal allergic rhinitis at 2 sprays in each nostril twice daily.(1) It is not available in Canada. (2)(3)(4)
References: 1. micromedex
2. DPD
3. cps
4. Pharmaclik

Apr. 3, 2017I have a 14 year old with generalized anxiety and migraines. She's on nortriptyline 25mg at bedtime. I'd like to start something for anxiety. Was planning on getting a baseline EKG and then start escitalopram (if insurance covers) or sertraline (if escitalopram isn't covered) at low dose and increase slowly to target dose of 10 escitalopram to 100 of sertraline over 6 weeks. Anything else I should be aware of? I discussed risk of serotonin syndrome.' details
 

Medical Problems: headaches
Medication History: nortriptyline 25mg hs
Response: Escitalopram is predicted to increase the exposure to nortriptyline. The serotonin syndrome has, rarely, been seen in patients given SSRIs with tricyclics. Nortriptyline has been associated with QT prolongation or torsade de pointes (mainly in overdose) but an effect is not established, whereas escitalopram has some risk of prolonging the QT interval. Some consider that concurrent use might increase the risk.

Since both citalopram and escitalopram are thought to be among the SSRIs least likely to alter the metabolism of other drugs, escitalopram is likely the best choice among the SSRI's to use with someone also taking nortriptyline. Monitor concurrent use for tricyclic toxicity (dry mouth, sedation, confusion), and adjust the dose if necessary. Some suggest a small initial SSRI dose. Increasing age, female sex, cardiac disease, and some metabolic disturbances (notably hypokalaemia) predispose to QT prolongation: in their presence consider ECG monitoring, which you are doing.

Escitalopram and citalopram are considered weak inhibitors of CYP2D6.
References: 1. Stockleys
2. lexicomp

Apr. 3, 2017Rabeprazole tablets are enteric coated and I am wondering why? Can they be crushed? details
 

Response: Rabeprazole is enteric coated because it is unstable in acidic media and undergoes pH-dependent decomposition especially rapidly below pH 4-5; therefore it should not be crushed. (1)
Alternative Formulations & Administration: - Capsules: dexlansoprazole, lansoprazole, omeprazole - Open capsules & sprinkle intact granules onto soft, cold food. Swallow immediately; do not crush/chew granules; Suspension from solid dosage form for po or NG tube: use dexlansoprazole, esomeprazole (tablet NEXIUM & some generics, granules), lansoprazole (capsule granules, FASTAB)(2)
References: 1. DPD - apo-rabeprazole monograph
2. RxFiles - Acid Suppression Drug Comparison Chart

Apr. 4, 2017Can you crush morphine IR? details
 

Response: Morphine IR can be crushed (2). Manufactuer says there is no specific kinetic/pharmacologic reasons for their warning, but rather it is based on abuse potential (3)
References: 2. ISMP do not crush
3. Manufactuer call to Purdue Pharma

Apr. 5, 2017We were at a nurses’ meeting today and the question came up about aspirin monitoring. What is the recommendation for low dose (81mg OD PO)? – The background to this question is, a resident was on low dose aspirin and she had melena recently (aspirin now on hold) details
 

Response: For low-dose aspirin, there are not any specific recommendations for monitoring, beyond what a patient would already have done. For example:
- Consider monitoring renal function periodically (every 6-12 months) in someone with compromised renal function, or at risk of poor renal function (eg. Diabetics, also on diuretics , other NSAIDs) -- these populations likely already have renal function testing done, so low dose ASA would not impact this. If a person has no risk factors for compromised renal function, then extra testing would not be necessary based on just being on ASA 81mg.
- Iron related lab tests would not be regularly indicated for someone on low-dose ASA. If a person has a history of anemia or GI bleeds / ulcers, then periodic monitoring would be reasonable (every 6-12 months)--otherwise, instructing the patient to watch for blood in the stool will be more effective in detecting a bleed than lab monitoring would be.
- For your patient, it is prudent to discontinue the ASA if a bleed does occur.
- Probably the most important aspect to sometimes re-evaluate is making sure a patient actually requires ASA 81, especially if it's just for primary prevention.
References: 1. Monograph for ASA 81mg
2. Micromedex, aspirin monitoring

Apr. 6, 2017Can dextromethorphan be used to effectively to treat anxiety accompanied by bouts of screaming and shouting? details
 

Response: A combination product, DM 20 mg/quinidine 10 mg, has been approved in the US for pseudobulbar affect.(2) Pseudobulbar affect is “characterized by sudden, unpredictable and involuntary episodes of crying, laughing, or other emotional displays that are exaggerated relative to or incongruent with the mood and feelings of the patients."(2) There is also very limited evidence of use in autism.(2)
The DM/quinidine product is not approved in Canada.(3) The quinidine is only included to exploit its CYP2D6 inhibition.(2,4)
References: 1. A placebo double-blind pilot study of dextromethorphan for problematic behaviors in children with autism. Woodard C, Groden J, Goodwin M, Bodfish J. Autism. 2007 Jan;11(1):29-41. PMID: 17175572
2. Pharmacol Ther. 2016 Mar;159:1-22. doi: 10.1016/j.pharmthera.2016.01.016. Epub 2016 Jan 28. Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders. Nguyen L1, Thomas KL2, Lucke-Wold BP3 PMID 26826604
3. NOC database
4. Lexicomp
*Clinical handbook of psychotropic drugs for children and adolescents, DrugDex, PubMed "dextromethorphan anxiety ";

Apr. 6, 2017We package bubble packs for long term care about a week in advance so those getting Florinef are at room temperature for ~35 days. The monograph says it can stay at room temperature for 30 days but a New Zealand site says 3 months. Will 35 days be okay? details
 

Response: Florinef is known to be stable up to 30 days at room temperature.(1-3) However, no stability beyond 30 days is available as studies of greater duration were not conducted.(3) It should be noted this product used to be stored at room temperature and storage recommendations were changed in ~2005, not based on reformulation but more sophisticated analysis techniques. (2)
References: 1. Previous phone communication with Marie, medical information, Paladin Labs 1 888-550-6060 #395 5/30/2008
2. Phone communication with Kayla, Paladin Labs, 1-888-550-6060 Jan 24/11
3. Phone communication with Julia, Paladin Labs, 1-888-867-7426 07 Apr 2017

Apr. 6, 2017Is there a place to look for metabolites of drugs of abuse? When a NP gets a urine screen back and sees results she often asks if it’s a metabolite of a drug the patient is taking. What about a morphine equivalent chart? details
 

Response: One resource that has fairly comprehensive list of metabolites is drugbank.ca
eCPS has an equivalent table in the dosage section of the CPhA Opioids monograph
Global RPh has two calculators - http://www.globalrph.com/narcoticonv.htm and http://www.globalrph.com/opioidconverter2.htm (for methadone)

Apr. 6, 2017A nursing home patient with partial gastric outlet obstruction and severe gastric reflux has been getting dilatation q4wks from surgeon and her pantoprazole dose was increased to 80 mg PO BID yesterday. The surgeon wants to know what can be used for breakthrough reflux. The monograph for Diovol Plus says it's contraindicated when distention is due to partial or complete gastric obstruction. What is the reason for this? If Diovol Plus really can't be used, what else could be tried? details
 

Patient Age: 82
Patient Sex: F
Medical Problems: severe reflux
partial gastric outlet obstruction - not completely emptying, severe gastric reflux
Medication History: pantoprazole started at 40 mg BID, increased to 60 mg BID 2 weeks ago and now surgeon is increasing to 80 mg BID
rosuvastatin 10 mg HS, candesartan 8 mg OD, pregabalin 75 mg BID, Slow K i bid, Symbicort
salbutamol,
PRNs: Gravol 50 mg, Anodan HC suppositories, lactulose, APAP 1000 mg TID PRN, Senokot-S artificial tear
reviewed non-pharmacological strategies. Surgeon wants to know what can use for breakthrough? Diovol? Monograph - Plus - CIs - alkalosis, where disteneion may be due to partial or complete gastric obstruction. Had been on 10 mL TID PRN but d/c and not sure why. Had been on domperidone d/c.
Response: While it is not stated in monographs, it would seem the reason for the contraindication of antacids in patients with intestinal obstruction may be due to risk of bezoar formation, which has been reported in earlier literature.(2-4) Reduced intestinal motility, dehydration, and reduced gastric acid have been proposed as reasons these patients experienced bezoar formation.(2-4) While larger doses are surely to increase risk (4), a report of bezoar formation in a patient taking 45 ml MgO twice per week in combination with a diuretic has been published.(2)
It seems reasonable to try an antacid at reocmmended doses followed by a full glass of fluid; this should be discontinued if it does not provide relief. Possibly bezoar formation can be monitored during dilatations.
References: 1. eCPS
2. Small bowel obstruction caused by a medication bezoar: report of a case. Tatekawa Y, Nakatani K, Ishii H, Paku S, Kasamatsu M, Sekiya N, Nakano H. Surg Today. 1996;26(1):68-70.
PMID: 8680127
3. Intestinal obstruction from medication bezoars. Korenman MD, Stubbs MB, Fish JC. JAMA. 1978 Jul 7;240(1):54-5. No abstract available. PMID: 307067
4. South Med J. 1986 Jul;79(7):917-8. Small bowel obstruction from an antacid bezoar: a ranitidine-antacid interaction? Burruss GL, Van Voorst SJ, Crawford AJ, PMID: 3726597

Apr. 6, 2017Any suggestions for alternatives to the IV lasix shortage besides PO lasix? It would be much appreciated to have another alternative to recommend to physicians. details
 

Response: Furosemide is available as an oral solution. Clearly it has a slower onset of effect (30-60 minutes) for diuresis compared to 5 minutes for IV.(6)
There is an available alternative to IV furosemide. Ethacrynic acid is a loop diuretic available as injectable (DIN 00268313).(3) The usual dose is 50 mg or 0.5-1 mg/kg (max 100 mg).(4,5) The problem is this product’s acquisition cost is $545 per dose (vials of 50 mg).(3) It can be irritating at the injection site so if a 2nd dose is required, it should be administered at a new site to reduce the risk of thrombophlebitis. It has a higher risk of ototoxicity than other loops and should be avoided in those with CrCl <10 ml/min.(5)
Unfortunately, the ethacrynic acid is the only other IV diuretic available in Canada.(2)
References: 1. eCPS - CPhA monograph
2. DPD
3. PHarmaClik
4. Ottawa Hospital Parenteral drug Manual
5. https://www.ashp.org/drug-shortages/current-shortages/Drug-Shortage-Detail.aspx?id=636 (including Table 2)
6. Lexicomp

Apr. 6, 2017We received a prescription for azithromycin 500 mg x 1 day then 250 mg x 1 month. (Prednisone prescribed as well.) What would be the indication for this length of therapy? details
 

Patient Age: 72
Patient Sex: M
Medical Problems: COPD
T2DM
Medication History: Spiriva, salbutamol,
statin, Lantus, metformin, amlodipine

clarithromycin 500 mg BID x 7 days, 10 days ago with prednisone
not sure if hospitalized
Response: Chronic, prophylactic antibiotics have been shown to reduce exacerbations in COPD compared to placebo in patients with moderate to severe COPD.(2,3) Azithromycin has been studied at 250 mg PO OD x 1 year (as well as a pulsed regimen).(3) However, this intervention would be considered after other means of reducing exacerbations have been instituted including inhaled corticosteroids.(3) Furthermore, it seems this patient may be experiencing an exacerbation at this time and prophylaxis was only started in patients who were exacerbation free for at least 4 weeks.(3) Assuming this is an exacerbation that did not respond to clarithromycin, azithromycin is not a good choice. If it is strongly felt the etiology is bacterial, amoxicillin-clavulanate is a better choice in this complicated patient.(1,2) If there is no response within 72 hours, consider sputum culture and reconsider etiology.(2)
References: 1. UTD - Management of exacerbations of chronic obstructive pulmonary disease - Outpatient management of exacerbations of COPD
2. CTC - Chronic Obstructive Pulmonary Disease
3. Herath SC, Poole P. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD). Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD009764. DOI: 10.1002/14651858.CD009764.pub2.

Apr. 6, 2017I'm wondering if there is any difference in efficacy between chewable and enteric coated aspirin in terms of primary and/or secondary prevention. From what I can tell, chewable aspirin seems like a better choice for acute/emergency situations, but I'm looking more for information regarding long-term use for prevention. Additionally, is enteric coated aspirin much safer in terms of preventing adverse effects like GI bleeds? details
 

Response: The reason for enteric coated ASA is to reduce dyspepsia. Because both formulations contain the same drug, there is no difference in terms of effectiveness for primary/secondary prevention between the two. When taken during a suspected MI, it is preferred to chew ASA for faster absorption; certainly chewables are easier to chew and taste better. The next best option in this case would be a regular tablet though enteric coated can be used if it's all that's available - it may be more difficult to chew.
The risk of GI bleed is a systemic effect of ASA and is not reduced by use of enteric coated products. As stated above, enteric coated products serve to reduce dyspepsia, but not reduce GI bleeding. (1)
References: 1. Canadian Pharmacist's Letter; November 2012; Vol: 19

Apr. 7, 2017We have rx for Kdur 20 mmol which has been d/c. We have Euro K 20 (DIN 02242261). Is this interchangable? details
 

Response: Euro-K 20 would be expected to act similarly as K-Dur as K-Dur is the brand reference(2); however, none of the potassium chloride products are interchangeable.(2)
References: 1. http://formulary.drugplan.ehealthsask.ca/
2. http://www.euro-pharm.com/en/products-detail_c.php?prodName=Euro-K+20&fromSearch=true
3. http://www.euro-pharm.com/en/products-detail_c.php?prodName=Euro-K+600&fromSearch=true
4. http://scp.in1touch.org/uploaded/web/refmanual/Regulatory_Bylaws_Current.pdf

Apr. 7, 2017I have a patient who cannot tolerate much exercise and I'm trying to figure out if either ivabradine or entresto would be worth trying to improve this? details
 

Patient Age: 83
Patient Sex: M
Medical Problems: CHF, AF, aortic valve stenosis.
EF and NYHF class not available
Never smoked, lived healthy all his life, ran until his hip replacement and then biked well into his 70's.
Medication History: Dig .125 mg daily, Atorvastatin 10mg daily, Diltiazem 120mg daily, ramipril 2.5mg daily, bisoprolol 5mg daily, spironolactone 25mg daily, Furosemide 40mg daily, Warfarin to keep INR btwn 2 and 3
Eltroxin 0.05mg daily
Response: Because of the presence of AF in your patient, ivabradine is not an option. (4,8)
Entresto could be considered, which is discussed below. However, some other tweaks can be made before considering Entresto:
1. Diltiazem worsens exercise tolerance (4,5,7) and therefore should be discontinued. Whether it’s being used for hypertension (though not listed as a medical condition) or AF, other drugs can pick up the slack.
2. The dose of ramipril is not optimal.(6,7) The target dose of ramipril in HF is 5 mg PO BID or 10 mg PO OD. Perhaps his dose has been limited by side effects such as hyperkalemia but this should be investigated.
3. The dose of bisoprolol is not optimal.(6,7) The target dose of bisoprolol in HF is 10 mg PO OD. Again, it is possible this dose has been limited by heart rate, his exercise intolerance and/or others. As such, concentrate on optimizing ramipril first.

Suggest to d/c diltiazem and look into optimizing the others as a first step. If after this his symptoms still persist, consider adding Entresto. Note: Entresto will REPLACE ramipril and ramipril needs to be discontinued at least 36 hours before starting Entresto to reduce the risk of angioedema.(1,8) EDS criteria for Entresto include:
For the treatment of heart failure (HF) with reduced ejection fraction in patients with New York Heart Association (NYHA) class II or III to reduce the incidence of cardiovascular (CV) death and HF hospitalization, if all of the following clinical criteria are met:
• Reduced left ventricular ejection fraction (LVEF) (<40%)
• Patient has NYHA class II-III symptoms despite at least four weeks of treatment with a stable dose of an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor antagonist (ARB) in combination with a beta-blocker and other recommended therapies, including an aldosterone antagonist (if tolerated).
• Plasma B-type natriuretic peptide (BNP) ≥ 150 pg/mL or N-terminal prohormone-B-type natriuretic peptide (NT-proBNP) ≥ 600 pg/mL; or plasma BNP ≥ 100 pg/mL or NT-proBNP ≥ 400 pg/mL levels if the patient has been hospitalized for HF within the past 12 months.
• Patients should be under the care of a specialist experienced in the treatment of HF for patient selection, titration, follow-up and monitoring.
(2)
Based on the extensive HF meds list, likely the first bullet is satisfied. The plasma B-type natriuretic peptide level will need to be investigated. Also the NHYA class will need to be confirmed. One note with Entresto is it caused more symptomatic hypotension than the comparator (enalapril) in the trials.(1)
References: 1. Zack’s presentation Drug Therapy Sep 2016
2. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf
3. http://www.onlinecjc.ca/article/S0828-282X(15)00475-4/pdf
4. Clinical Resource, New Drug: Lancora (Ivabradine). Pharmacist’s Letter/Prescriber’s Letter. April 2017.
5. PL Detail-Document, Improving Heart Failure Care. Pharmacist’s Letter/Prescriber’s Letter. February 2016.
6. PL Detail-Document, Target Doses of Meds for Systolic Heart Failure. Pharmacist’s Letter/Prescriber’s Letter. November 2013.
7. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-Heart-Failure.pdf
8. PM from DPD

Apr. 7, 2017If a baby has failed oral nystatin for thrush, what is the next step? details
 

Medical Problems: 2 month old

oral thrush

22 days ago
9 days ago
Medication History: nystatin oral suspension x 7 days (2 courses; 2nd course started 6 days after the end of the 1st cours).
Response: It is possible the nystatin was not used optimally. Nystatin should be used for 7-14 days (1,3,6) until 2 days after the infection has cleared.(2,3) If the child's symptoms had not been cleared for at least 2 days at the end of the last course, a third course of 1-2 ml QID (3,4,6) for 7 days or until 2 days after symptoms resolution, whichever comes later, can be considered. If the nystatin has been used appropriately, fluconazole 3 mg/kg is listed in pediatric references for oropharyngeal candidiasis in infants one month old and up. (5,7) If the mother has symptoms of candidiasis on her nipples, it may be more effective to use a cream such as clotrimazole or nystatin for greater contact time, though there is nothing to suggest the suspension would not be effective. If the mother does not have symptoms, there is no need to switch from the suspension.
Furthermore, toys, pacifiers, feeding bottles/nipples should be sterilized to prevent re-infection.(1,3)
References: 1. CTMA - Oral Candidiasis
2. http://www.caringforkids.cps.ca/handouts/thrush
3. Dynamed - Oral candidiasis in infants
4. Canadian Pharmacist's Letter 2016; 32(12):321231
5. SickKids drug handbook
6. Bugs and Drugs
7. BNF for children 2016-2017

Apr. 7, 2017Wondering if you can help me better understand the possible effects of pregabalin in the developing brain. I treat children and adolescents, and occasionally use pregabalin to treat anxiety when other agents have been found ineffective. A patient found this article: http://fibromyalgiaawareness.info/2017/03/27/clinical-research-finds-neurontin-lyrica-death-sentence-new-brain-synapses/ It certainly is inflammatory and seems to exaggerate concerns, however it claims that pregabalin inhibits new synapses from forming. It's based on this study: http://www.cell.com/cell/abstract/S0092-8674(09)01185-4?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867409011854%3Fshowall%3Dtrue I'm having a hard time differentiating truth from hype. Can you help me understand -- is this something that is being over exaggerated or something that should give me pause before prescribing to the developing brain. One of my colleagues told me, "prevention of excitatory effects is probably a feature and not a bug." details
 

Response: The underlying premise of the article is that inhibiting synapse formation is harmful. Certainly I understand that first impression – wouldn’t one stagnate, or worse, regress if synapses are no longer being formed? How can that not have deleterious effects on cognition/learning/development?

In my reading, it seems part of the pathogenesis of epilepsy (1-4), neuropathic pain (1-4), and possibly anxiety (5 is ‘rogue’ synapse formation. In other words, synapses are being formed uncontrollably (or at least aberrantly), causing disease. So, while the animal studies indicate pregabalin and gabapentin do inhibit synaptogenesis, in this sense they are controlling chaos as opposed to interfering with normal development.

Obviously the brain is an extremely complex organ of which humans maybe understand 1% - and of that I may understand 0.001%! As such, I make no claims that gabapentinoids do not or cannot cause long-term negative effects on neuropsychiatric development. All drugs carry risks and these risks are amplified in the pediatric population due to their intense state of development (of all facets) as well as the dearth of medical studies conducted in them. It always comes down to risk vs. benefit.

This study by no means proves gabapentinoids are harmful to the neurodevelopment of a child or adolescent. To me, it does give reason for pause – that there is much we don’t understand about the body and drugs. For this reason the usual tenets of drug use apply:

- use pharmacotherapy only when non-pharmacological strategies are ineffective
- use the lowest effective dose; if no benefit is documented, discontinue
- treat for the shortest duration possible; if benefit has been achieved, discontinue periodically to assess for ongoing need
References: 1. Dolphin AC. Calcium channel α2δ subunits in epilepsy and as targets for antiepileptic drugs. In: Noebels JL, Avoli M, Rogawski MA, et al, editors. Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
2. Risher M, Sexton H, Risher W, et al. Adolescent intermittent alcohol exposure: dysregulation of thrombospondins and synapse formation are associated with decreased neuronal density in the adult hippocampus. Alcohol Clin Exp Res. 2015 Dec;39(12):2403-13.
3. Toth C. Pregabalin: latest safety evidence and clinical implications for the management of neuropathic pain. Ther Adv Drug Saf. 2014;5(1):38-56.
4. Eroglu Ç, Allen NJ, Susman MW, et al. The gabapentin receptor α2δ-1 is the neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell. 2009;139(2):380-392.
5. Baldwin DS, Ajel K, Masdrakis VG, Nowak M, Rafiq R. Pregabalin for the treatment of generalized anxiety disorder: an update. Neuropsychiatr Dis Treat. 2013;9:883-92.

Apr. 7, 2017Patient experiences leakage of insulin even after holding needle in place for 15 seconds. Would switching to a longer needle help or is there another issue to address? details
 

Patient Age: 50
Patient Sex: M
Medical Problems: T2DM
Medication History: Lantus
Insupen Needles 32G 4mm
Response: The resounding consensus is needle length has no effect. I have outlined some strategies to manage and information that I gathered from these references. There is conflicting information about what angle to hold the pen, but there are several other suggestions. Your patient may already be practicing all these strategies in which case the information may be more helpful (basically reassurance that it’s not typically a problem).

Strategies to reduce leakage
- Leave pen in for 10 seconds to prevent leakage(1,2)
- After removing needle, place finger on site for 5-10 seconds (1)
- Always remove the needle from the pen after injection(1-3); leaving the needles attached can cause air to enter the cartridge and it will take longer to inject the insulin (1) or affect the dose (2)
- Try injecting at 45-degree angle rather than 90 (1)
o however, another says: 4-mm needle should be inserted at 90 degrees, not an angle (2)
- Larger doses may be split to reduce the volume of insulin (2)
- Use needles with thin-wall or extra-thin-wall technology (2,4)
- Direct observation of self-injection is important for those who report frequent skin leakage.(2)

Information about leakage
- Leakage following withdrawal of the needle is not unusual.(1)
o usually the amount is clinically insignificant.(1,2)
- Insulin appearing on the skin after removing needle = backflow (5)
o occurs with both syringes and pens (5)
o occurs with all needle gauges (5)
o occurs with all needle lengths (2,4-6)
o occurs with all body compositions (4,5)
- Studies show backflow is a consistent percentage of the injection such that as the dose increases, the percentage of backflow increases so this does not interfere with dose adjustment. (5)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Diabetes-Insulin-ManagmentTool.pdf
2. http://www.rxfiles.ca/rxfiles/uploads/documents/Insulin-Longer-Shorter-InfoGraphic-RxFiles.jpg
3. Dubois W. Everything you wanted to know about injecting insulin. Diabetes Self Management. [updated 04 Oct 2016; cited 07 Apr 2017] Available at https://www.diabetesselfmanagement.com/managing-diabetes/treatment-approaches/everything-you-ever-wanted-to-know-about-injecting-insulin/
4. Campbell A. Injecting insulin: tips for success. [11 Jul 2016; cited 07 Apr 2017]. Available at https://www.diabetesselfmanagement.com/blog/injecting-insulin-tips-success/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380785/
6. http://www.sciencedirect.com/science/article/pii/S0025619616303214
7. http://journals.sagepub.com/doi/pdf/10.1177/0145721716648017
8. https://www.diabeteseducator.org/docs/default-source/legacy-docs/_resources/pdf/research/injectioneducationpracticeguide.pdf?sfvrsn=2

Apr. 7, 2017What is the final volume of vancomycin injectable when reconstituted? DIN 02394634, 1 g vial. details
 

Response: Reconstitute the 1 g vial with 20 ml sterile water for injection to provide ~50 mg/ml. (1)
References: 1. Product monograph from DPD

Apr. 7, 2017How long can the client be off the tamsulosin and not end up with urinary retention again? Is there an another option to use? Upcoming cataract surgery and concern with floppy iris syndrome. details
 

Patient Age: 76
Patient Sex: M
Medical Problems: Post CVA several years lives at home. Had significant urinary retention post stroke and now continent on tamsulosin.
Booked for cataract extraction and was told to be off it for a month. has two eyes so will likely be up to three months off the med.
Medication History: Tamsulosin 0.4 mg daily
Senokot S 2 tabs daily
Omeprazole 20mg daily
citalopram 20 mg daily
Response: Bottom line: the most current guidelines state discontinuation of alpha-1 blockers prior to cataract surgery does not prevent intraocular floppy iris syndrome (IFIS). In the case of a patient established on tamsulosin therapy and requiring cataract surgery, mitigating factors lie largely with the surgeon. Switching to a less selective alpha-antagonist would seemingly be a good compromise of risk reduction and maintenance of control of lower urinary tract symptoms (LUTS); however, there is no evidence to support this strategy.
--------------
The half-life of tamsulosin is approximately 14-15 hours2 such that return of urinary symptoms would be expected to start about 48 hours following discontinuation. Other drugs used for LUTS include other alpha-1 blockers, 5-alpha-reductase inhibitors, antimuscarinics in combination with alpha-1 blockers and tadalafil.3 Switching agents prior to surgery is unlikely to be an effective strategy based on pharmacology of some of the other agents but mainly due to the reported long-term effect of tamsulosin on the risk of IFIS.

The effects of tamsulosin on the iris have been reported to occur even several years after discontinuation,2,4-7 likely because some of the effects are irreversible.5,8 Apparently, though, in most cases, the discontinuation had been only 2-14 days prior to surgery.2 Tamsulosin appears to have a greater impact on IFIS than other alpha-1 antagonists5 which could be because it is the only alpha blocker selective for the 1a receptor - which dominates the iris dilator muscle8- and has the greatest affinity for this receptor subtype. However, it needs to be mentioned the estimate of the hazard ratio of tamsulosin compared to other alpha blockers has been wide from study to study which could be because in most studies either the tamsulosin cohort was significantly larger than the others or the cohort in general was small.5 A case-control study found moderate-to-severe IFIS was statistically significantly more common in patients taking tamsulosin (34.3%) than alfuzosin (16.3%) and no alpha blockers (4.4%).9

The most recent ASCRS and AAO Educational Update Statement (2014) makes no recommendation to switch alpha blockers and clearly states, "It is well recognized that simply discontinuing oral α1‐antagonists does not prevent IFIS." 1 The effect is that the surgery may be more difficult but surgical techniques are recommended to overcome the challenges.5,8 Intuitively, one may consider switching tamsulosin to alfuzosin – an alpha blocker not selective for 1a - in hopes that effects are reversible in this particular patient and that alfuzosin will not induce the same changes. Unfortunately, the only research to address this is a small case series published in abstract only.10 These researchers switched patients from tamsulosin to alfuzosin (n=5; 9 eyes) four weeks prior to surgery and found 7 of the 9 eyes to be suboptimally dilated prior to surgery and 7 had undulating iris with subsequent iris prolapse. Of course, given the sample size and uncontrolled nature of this report, one could argue it’s possible the complications were reduced by switching to alfuzosin.

I realize this leaves you in a difficult position. What is known with near certainty is your patient’s LUTS is likely to start worsening within several days of tamsulosin discontinuation. There is also a good chance his use of tamsulosin will complicate the surgery. What is certainly less clear is if tamsulosin discontinuation prior to surgery does reduce the risk of IFIS significantly (we know it doesn’t eliminate the risk). Furthermore it is unclear if substitution with alfuzosin allows for continued LUTS control and a lower risk of IFIS than continued use of tamsulosin. The research to date suggests likely not on both of these last points, but it is too limited to make conclusions. Hopefully with this information you, your patient and the surgeon can reach a best-fit solution.
References: 1. eCPS
2. Clinical Key: BOOK CHAPTER Cataracts. R. Scott Hoffman M.D. Ferri's Clinical Advisor 2017, 251-252.e1
3. Handzel DM, Briesen S, Rausch S, Kälble T. Cataract Surgery in Patients Taking Alpha-1 Antagonists: Know the Risks, Avoid the Complications. Deutsches Ärzteblatt International. 2012;109(21):379-384. doi:10.3238/arztebl.2012.0379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371631/#!po=45.0000
4. Prospective masked comparison of intraoperative floppy iris syndrome severity with tamsulosin versus alfuzosin. Chang DF, Campbell JR, Colin J, Schweitzer C; Study Surgeon Group.. Ophthalmology. 2014 Apr;121(4):829-34. doi: 10.1016/j.ophtha.2013.10.031. Epub 2013 Dec 4. PMID: 24314842
5. Cardiovascular and ocular safety of α1-adrenoceptor antagonists in the treatment of male lower urinary tract symptoms. Oelke M, Gericke A, Michel MC. Expert Opin Drug Saf. 2014 Sep;13(9):1187-97. doi: 10.1517/14740338.2014.936376. Epub 2014 Jul 29. Review.PMID: 25073735
6. ASCRS and AAO Educational Update Statement; Intraoperative Floppy Iris Syndrome (IFIS) Associated with Systemic Alpha‐1 Antagonists - Apr 2014 https://www.aao.org/clinical-statement/intraoperative-floppy-iris-syndrome-ifis-associate-2
7. CTC - Norman R, 01 Jun 2015; Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia
8. Storr-Paulsen A, Nørregaard JC, Børme KK, et al. Intraoperative floppy iris syndrome (IFIS): a practical approach to medical and surgical considerations in cataract extractions. Acta Ophthalmol. 2009 Nov;87(7):704-8. PMID 19558575
9. Skorin L. How to avoide intraoperative floppy iris syndrome. Rev Optomet. 2010 Nov; available at https://www.reviewofoptometry.com/article/how-to-avoid-intraoperative-floppy-iris-syndrome
10. Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg 2005;31:664-73. PMID: 15899440
11. Blouin MC, Blouin J, Perreault S, et al. Intraoperative floppy-iris syndrome associated with alpha1-adrenoreceptors: comparison of tamsulosin and alfuzosin.J Cataract Refract Surg. 2007 Jul;33(7):1227-34.
12. Jan Teper S, Dobrowolski D, et al. Complications of cataract surgery in patients with BPH treated with alpha 1A-blockers.Cent European J Urol. 2011;64(2):62-66. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921715/
13.Chan T, O'Keefe P, Mather R. Can switching tamsulosin to alfuzosin prevent intra-operative floppy iris syndrome in patients with benign prostate hypertrophy?; Paper #P-00051. Canadian Ophthalmological Society Annual Meeting; Quebec: 2010. http://www.cos-sco.ca/annualmeeting/2010/program/COS2010AbstractBook.pdf
*Dynamed

Apr. 11, 2017I have a 69 yo female patient with a history of breast cancer (remission since 2012) wanting to use Vagifem for post-menopausal vaginal atrophy. Is this okay? details
 

Patient Age: 69
Patient Sex: FEMALE
Medical Problems: Post menopausal vaginal atrophy
Breast Cancer (2012)
Medication History: tomoxifen
synthroid
vitamins
asa 81
Response: Product monograph of course contraindicates in women with past or previous breast cancer history. However, in February 2017 The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists (ACOG) has issued an opinion in support of vaginal estrogen in breast cancer survivors.

Nonhormonal treatments remain first-line therapy. The committee found that vaginal estrogen usually has minimal systemic absorption and delivers lower doses of estrogen closer to normal menopausal levels. While acknowledging controversy about recurrence risk with the use of vaginal estrogen in women with breast cancer who are receiving aromatase inhibitors, the committee concludes that such women "may benefit" from short-term topical estrogen combined with tamoxifen, followed by a return to aromatase inhibitors. Current data indicate no increased risk for recurrence among women receiving tamoxifen, they write.

The committee also emphasizes an individualized approach and informed decision making, in which women can thoroughly weigh the risks and benefits of vaginal estrogen in coordination with an oncologist.
(1)
The North American Menopasue Society support use in consultation with an oncologist.
(2)
References: 1. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013;20(9):888–902.DOI:10.1097/GME.0b013e3182a122c2

2. Veronica Hackethal. ACOG Supports Vaginal Estrogen in Breast Cancer Survivors. Obstet Gynecol. 2016;127:e93-e96.

Apr. 11, 2017Can I add on a CCB like Adalat for my patient? She really loves grapefruit juice and has a prolonged QT interval. details
 

Patient Age: 30
Patient Sex: FEMALE
Medical Problems: Essential HTN
Prolonged qt- sent to internist
Medication History: Marvelon
Coversyl Plus- responded well but needs additional lowering.
Response: Suggested amlodipine instead as grapefruit interaction is not thought to be clinically significant (1). No QT prolongation for amlodipine. Advised to be extra conservative could start at lower dose and titrate up while monitoring for hypotension and tachycardia, but again this interaction is not thought to be clinically significant (7-16% increase). (1)
References: 1. Stockley's Drug Interactions- Nifedipine and Grapefruit Juice
2. RxFiles- CCBs
3. RxFiles QT Prolongation

Apr. 12, 2017Could you check into the area of meningococcal vaccine in pregnancy? Previously, the polysacharide has been the one recommended. However, with the variety of conjugates now available, there might be more/better information on other suitable options. details
 

Response: One resource suggests conjugated meningococcal vaccine is preferred over polysaccharide in pregnant women(2); however, this statement was not referenced and not found elsewhere. One study has been published containing 103 reports of meningococcal conjugate vaccine exposure during pregnancy to the Vaccine Adverse Events Reporting System, in which no safety concerns were identified.(11)
Recommendations of agencies:
PHAC - "the use of conjugate meningococcal vaccines in pregnancy may be considered" (9) There is no mention of polysaccharide vaccine in pregnancy so perhaps this is an endorsement of the conjugated.
CDC -"pregnancy should not preclude vaccination with MenACWY or MPSV4, if indicated" (4)
WHO- "both conjugate and polysaccharide vaccines are efficacious and safe when used in pregnant women"(10)
References: 1.https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-16-pneumococcal-vaccine.html#a15
2. Clinical Key - Schaeffer -Vaccines and immunoglobulins Benedikte-Noël Cuppers and Christof Schaefer, Drugs During Pregnancy and Lactation, 2.7, 177-192
3. Brigg's
4. https://www.cdc.gov/vaccines/pregnancy/hcp/guidelines.html
5. Elwood C, Immunization in pregnancy. Presentation https://fmf.cfpc.ca/wp-content/uploads/2016/11/T136622_Immunization-in-Pregnancy.pdf
6. UTD - Immunizations during pregnancy - Barss V.
7. Maternal immunization with pneumococcal 9-valent conjugate vaccine and early infant otitis media. Daly KA, Scott Giebink G, Lindgren BR, Knox J, Haggerty BJ, Nordin J, Goetz S, Ferrieri P. Vaccine. 2014 Dec 5;32(51):6948-55. doi: 10.1016/j.vaccine.2014.10.060. Epub 2014 Oct 30. PMID: 25444821
8. Chaithongwongwatthana S, Yamasmit W, Limpongsanurak S, Lumbiganon P, Tolosa JE. Pneumococcal vaccination during pregnancy for preventing infant infection. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.: CD004903. DOI: 10.1002/14651858.CD004903.pub4.
9. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-13-meningococcal-vaccine.html#p4c12a3
10. Wkly Epidemiol Rec. 2011 Nov 18;86(47):521-39. Meningococcal A conjugate vaccine: updated guidance, November 2011. PMID 25702330 http://www.who.int/wer/2011/wer8647.pdf?ua=1
11. Zheteyeva Y, Moro PL, Yue X, et al. Safety of meningococcal polysaccharide-protein conjugate vaccine in pregnancy: a review of the Vaccine Adverse Event Reporting System. Am J Obstet Gynecol 2013;208:478.e1-6.
12. https://mothertobaby.org/fact-sheets/meningococcal-disease-bacterial-meningitis-vaccine-pregnancy/
13. http://www.immunize.org/catg.d/p4210.pdf
14. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/mening.html
15. https://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/meningococcal-disease
16. Vaccine. 2012 Jul 6;30(32):4717-8. doi: 10.1016/j.vaccine.2012.04.093. Epub 2012 May 20. Pneumococcal vaccines WHO position paper - 2012 - recommendations. WHO Publication. PMID 22621828

Apr. 13, 2017Client takes lamotrigine and clobazam. She would like to take doxycycline as her antimalarial. Is this okay? details
 

Medical Problems: travel to malarial area
seizure disorder
Medication History: lamotrigine, clobazam
Response: This is not a problem. While some anticonvulsants induce doxycycline metabolism, neither lamotrigine nor clobazam do.(1-3)
References: 1. Stockley's
2. Lexicomp
3.Updated Malarial Screening Tool, Jun, 2016

Apr. 13, 2017I have a question about the use of hormones/contraceptive use to delay menstruation. I have a 21 year old female, who was contraindicated for COC-birth control use due to migraines with aura. She had a Mirena IUD inserted a couple of months ago and is returning for follow up at 10am this morning. The issue is that her wedding date falls around her regular menstrual period and we have been trying to find a way to delay it by a few days. Norethisterone is used in the UK, but not here, so I am out of ideas. details
 

Patient Sex: F
Response: For future reference, I often recommend norethindrone (=norethisterone) (Norlutate®) in appropriate patients, based on the UK indication. However, norethindrone is metabolized to ethinyl estradiol (EE); when taking Micronor (norethindrone 0.35 mg daily), the amount of EE generated is negligible. However, in a woman taking 15 mg norethindrone daily, research suggests about 25 mcg EE would be generated.(2)

Unfortunately, as you state, options in this patient are limited. The next best option is based on one very small open-label study in which medroxyprogesterone 10 mg TID taken on days 12 to 25 was as effective as norethindrone 5 mg TID taken on days 12 to 25 at reducing heavy menstrual bleeding.(2) This is a different situation than that of the patient. Theoretically, taking the MPA 2-3 days before the expected onset of bleeding, as one does with norethindrone, should delay bleeding. If the wedding is not before the patient's next cycle, she could experiment beforehand.

Otherwise, I find no other options. NSAIDs taken at therapeutic doses (e.g. naproxen 250-500 mg BID) should reduce bleeding but would not be expected to stop altogether or delay.(4)
References: 1. Lexicomp
2. J Fam Plann Reprod Health Care. 2012 Jul;38(3):148-9. doi: 10.1136/jfprhc-2012-100345. Epub 2012 Jun 12. Safer prescribing of therapeutic norethisterone for women at risk of venous thromboembolism. Mansour D1. PMID 22691698 http://jfprhc.bmj.com/content/early/2012/06/11/jfprhc-2012-100345.full
3. http://www.dorsetccg.nhs.uk/Downloads/aboutus/medicines-management/Other%20Guidelines/Delaying%20menstruation%20during%20holidays.pdf
4. UTD - Management of abnormal uterine bleeding

Apr. 18, 2017For Raynaud's Syndrome, what can be used to help with extremely red, hot feet / legs? details
 

Patient Age: 58
Patient Sex: F
Medical Problems: Raynaud's Syndrome
Medication History: Diltiazem CD 120mg Daily
Atorvastatin 40mg Daily
Rabeprazole 20mg Daily
Response: The evidence for pharmacological treatment of Raynaud’s phenomenon (RP) is quite weak. Nonetheless, dihydropyridine calcium channel blockers (DHP CCB) are considered more effective than non-DHP CCBs. (1-3) As such, it may be advantageous for your patient to be switched to nifedipine XL (30-120 mg daily), felodipine (5-10 mg daily) or amlodipine (5-10 mg daily). Typically symptoms of RP are triggered by cold or emotional stress. (1-3) If she has regular exposure (e.g. the outdoor temperature triggers attacks and she goes for walks daily at the same time), it may be helpful for her to take the dose 30-60 minutes before encountering the trigger. The other consideration is perhaps the red, hot feet are indicative of an underlying pathology also related to the RP symptoms.

Agents with even less evidence include phosphodiesterase-5 (PDE-5) inhibitors, prazosin and topical nitrates. Prazosin is likely to cause more problems with your patient’s BP than the diltiazem and PDE-5 inhibitors may be cost-prohibitive. Dosing is as follows1,3:
PDE-5 inhibitors: sildenafil 50 mg PO BID; vardenafiil 10 mg PO BID; or tadalafil 20 mg every other day or 5 mg PO once daily
topical nitrate ointment 2%: ¼ to ½ inch applied topically once daily
prazosin: 1-2 mg PO BID

I’m sure your patient is well-versed on the non-pharmacological methods but perhaps something in here she has not tried (1-3):
- minimize cold exposure; avoid sudden temperature changes and cold breezes
- dress warmly (including head and neck) and use warming devices in mitts/boots
- smoking cessation if applicable
- during attacks, vasodilation can be increased by:
- placing hands under warm water
- promoting distal blood flow to fingers by swinging arms vigorously (windmill effect) or raising arms above shoulders and forcefully swinging across body
- avoid carrying bags by handles, which may reduce blood circulation to fingers
- consider using general relaxation techniques to minimize emotional stress
References: 1. RxTx[Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. Roussin A. Raynaud’s phenomenon; [updated 01 Mar 2017; cited 18 Apr 2017].Available from: https://www.e-therapeutics.ca/
2. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 -2017. Record No. 115788, Raynaud phenomenon; [updated 18 Aug 2016, cited 18 Apr 2017]; [about 11 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=115788&site=dynamed-live&scope=site. Registration and login required.
3. Rothaus C. Rayaud’s phenomenon. Now@NEJM. 11 Aug 2016; cited 18 Apr 2017. Available at http://blogs.nejm.org/now/index.php/raynauds-phenomenon/2016/08/11/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+Nownejm+%28Now%40NEJM%29
*CPG

Apr. 19, 2017Patient brought these medications from Mexico -- "ASIP" and "ASMAPRET" -- any idea what they are? details
 

Response: 1. I've searched every variation of what those names look like, and cannot find anything. Verify spelling, try to get dosage and milligram strength to help.

Asipral = azithromycin in Chile
Asmapax = ephedrine + theophylline in the UK
Aspmapen = theophylline in Brazil
(4)
References: 1. MIMS
2. Lexi-international
3. Google search
4. Micromedex
*http://www.who.int/selection_medicines/country_lists/Mexico_medicamentos2009.pdf, http://www.saludymedicinas.com.mx/directorio-de-servicios/medicinas/

Apr. 20, 2017What is the optimal anti-coagulation regimen for someone with antiphospholipid syndrome? Received a prescription for Arixtra 10mg and all McKesson carries is 2.5 and 7.5 mg, which means she has to inject herself twice daily. Is there a 10 mg syringe? details
 

Patient Age: 34
Patient Sex: F
Medical Problems: kidney function normal
clotting disorder but until recently not clinically symptomatic
tested positive for lupus anticoagulant markers but no official dx Lupus
no weight change
Medication History: failed on warfarin, tinzaparin (during pregnancy), Xarelto (i.e. throws clots), then back on tinzaparin in Nov 2016 - threw several clots
Dec 2016 - started fondaparinux 7.5 mg + Plaquenil (not tolerating so stopped)
last week said bumped up to 10 mg (maybe bc Plaquenil d/c?)
Response: This patient did not disclose the actual bleeding disorder, though her history suggests it may be antiphospholipid syndrome (APS).(8) As such, the following information pertains to APS. Secondary thrombosis prophylaxis is usually undertaken with warfarin(5,6,8); whether the target INR should be 2.5 or 3.5 is under debate.(6,8) This is one area that could be investigated. Following warfarin, therapies typically go to heparins or direct acting anticoagulants(6,8), though trials are ongoing, but none have been published.(8) No discussion of management following failure of all three of these agents was found. Indeed, only one case report of fondaparinux for APS was found (10); the patient, an adolescent, was given 7.5 mg daily. 7.5 mg daily is the VTE treatment dose of fondaparinux for patients weighing 50-100 kg; 10 mg is treatment dose for those > 100kg (2)
Other agents are discussed including hydroxychloroquine (HCQ),(6) which is thought to reduce thrombosis and considering many patients with APS have concurrent lupus, it is a reasonable agent. Otherwise, biologics such as rituximab may be considered, though immunotherapy is only considered in those who need them for other reasons (e.g. lupus nephritis.(5,6) Immunotherapy does not provide any carry-over effect so needs to be taken on a long-term basis along with anticoagulation (in those who have already experienced a VTE.(5)
The treatment course this patient has followed seems very logical. There is also some logic to increasing fondaparinux after discontinuing HCQ, since HCQ could have some VTE prophylactic properties. As such, nothing revolutionary can be recommended. Perhaps the patient was not adherent with previous treatments and the requirment for two injections per day could motivate her to be adherent? This should be investigated for all of the agents. Also, her intolerance of HCQ should be explored to see if it could be managed and/or if it would be something expected to abate with time. Again, she may be more willing to put up with these effects if it means reducing the number of injections. Finally, what about considering a DOAC with a different MOA? Dabigatran has a different MOA to that of rivaroxaban, which has the same MOA of fondaparinux.(2) Certainly there is no evidence to suppport this strategy.
References: 1. DPD
2. eCPS
3. Phone communication with GND Distribution (how answered when called Aspen PharmaCare, who took over Arixtra in Jan 2017) 1-877-827-1306, Apr 20, 2017
4. [Recurrent thromboembolisms despite full anticoagulation in a patient with antiphospholipid syndrome]. Wernicke S, Selleng K, Felix SB, Greinacher A, Hammer F. Internist (Berl). 2017 Mar 6. doi: 10.1007/s00108-017-0211-6. [Epub ahead of print] German. PMID: 28265683
5. Antiphospholipid syndrome. Cervera R. Thromb Res. 2017 Mar;151 Suppl 1:S43-S47. doi: 10.1016/S0049-3848(17)30066-X. PMID: 28262233
6. Prevention of Recurrent Thrombosis in Antiphospholipid Syndrome: Different from the General Population? Legault KJ, Ugarte A, Crowther MA, Ruiz-Irastorza G. Curr Rheumatol Rep. 2016 May;18(5):26. doi: 10.1007/s11926-016-0573-0. Review. PMID: 27032789
7. RxTx - CTC - Venous Thromboembolism Jan 2017. Wells P, Forgie M.
8. http://thrombosiscanada.ca/?page_id=18# (each identified thrombophilias)
9. Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in antiphospholipid syndrome. Noel N, Dutasta F, Costedoat-Chalumeau N, et al. Autoimmun Rev. 2015 Aug;14(8):680-5. doi: 10.1016/j.autrev.2015.03.007. Epub 2015 Apr 9. Review. PMID: 25864630
10. Use of fondaparinux in a patient with antiphospholipid antibody syndrome and heparin-associated thrombocytopenia. Holtan SG, Knox SK, Tefferi A. J Thromb Haemost. 2006 Jul;4(7):1632-4. No abstract available. PMID: 16839370

Apr. 20, 2017I have a patient with a sulfa allergy. Is this okay with Proctol, which contains framycetin sulfate? details
 

Medical Problems: allergy to sulfa antibiotic
Response: Sulfa allergy refers to sulfonamide antibiotic or sulfonamide non-antibiotic reactions; while hypersensitivity reactions can be experienced following expsoure to sulfites and sulfates, they are not cross-sensitive to sulfa antibiotic or sulfa non-antibiotics.(1)
References: 1. Lexicomp - Sulfonamide Antibiotic Allergy (Drug Allergy and Idiosyncratic Reactions)

Apr. 20, 2017Is there an interaction between Malarone and St. John's wort? details
 

Response: No. St. John's Wort potentially interacts with chloroquine, mefloquine and doxycycline (CYP3A4 substrates), but not Malarone.(1)
References: 1. Travel Clinic Nurses' Tool updated 2016 Jun

Apr. 20, 2017A patient is getting Prolia today. Can she get Zostavax in the next few days? details
 

Response: Denosumab acts on a receptor called RANKL, which is related to TNFα;(1) other drugs that act on TNFα do cause immunosuppression. However, the fact the receptors are related does not mean they have the same action. No precautions or contraindications are available in monographs or other literature with respect to denosumab and live vaccines.(2-6) The manufacturer has been contacted in the past regarding any concerns of denosumab with live vaccines told simply that in the trials participants were not told to avoid live vaccines(7); however, there is also no data on how many participants did receive live vaccines during the trials and their outcomes. There is not enough evidence to avoid vaccination (live or otherwise) in patients on denosumab but at the same time, it is something to monitor in hopes of finding some more definitive information. (1)
References: 1. http://www.hindawi.com/journals/scientifica/2013/125705/
2. AHFS
3. PubMed
4. Lexicomp
5. DrugDex
6. eCPS
7. Phone communication with Valerie, Amgen Medical Information, Jan 21, 2016 1-866-50AMGEN (502-6436)

Apr. 20, 2017What is the evidence for use of phenytoin in trigeminal neuralgia? Are there any guidelines or studies for typical doses used or doses with effectiveness? Studies that include when a patient is on carbamazepine as well possibly. Would like some evidence to help support what kind of doses should be using for this indication? details
 

Medical Problems: uncontrolled trigeminal neuralgia
Medication History: Carbamazepine 600 mg BID, gabapentin 600 QID and phenytoin added on the weekend (loaded with IV 1500 mg, then has been on 300 mg IV BID since April 16).
Response: The American Academy of Neurology/European Federation of Neurological Societies practice parameter on treatment of trigeminal neuralgia consider carbamazepine (CBZ), oxcarbazepine (OXCB), and lamotrigine (LMG) as agents with evidence to support use in TN.(1) The following are considered to have insufficient evidence to support or refute efficacy: clonazepam, gabapentin, phenytoin (PHT), valproate, IV medications.(1)

RCTs are available for CBZ, OXCB, and LMG, whereas only uncontrolled evidence is available for PHT. The evidence supporting PHT is based on three uncontrolled studies involving a total of 30 patients. (2-4) Nearly all patients took 300 mg daily, though up to four took 400 mg daily. Of the 30 patients, 16 experienced complete pain relief, 7 partial pain relief, and 6 no effect.

I was unable to locate any case reports/studies of CBZ + PHT used for trigeminal neuralgia to give dosing guidelines with the combination. In general, when CBZ has been added to PHT, it has had variable effects on PHT levels; when PHT has been added to CBZ, CBZ levels tend to decrease and levels of the active metabolite, CBZ-10,11-epoxide (also responsible for toxicity) have increased.(5) As such, CBZ dose may need to be increased to maintain the current analgesic effect, but this is at the risk of greater adverse effects (more than additive). While in some studies LMG has not affected CBZ levels, in a study of three patients, it increased CBZ-10,11-epoxide without affecting CBZ levels; two of these patients developed symptoms of toxicity.(5)

Based on the greater level of evidence and potentially less complicated interactions with CBZ, LMG may want to be considered. Unfortunately, I do not have access to the paper in which LMG was added to CBZ. According to the abstract, patients were maintained on steady state CBZ and LMG was titrated from 50 to 400 mg/day.(6) There is no information available as to adjustment of CBZ or if all patients achieved the 400 mg daily LMG dose. UpToDate suggests for patients taking enzyme inducing drugs, including CBZ, to start LMG at 50 mg daily, titrating upward as needed to 100 mg daily at week 3, 200 mg daily at week 5, 300 mg daily at week 6, and 400 mg daily at week 7.(7) This is a much slower titration than the study above considering the combination was only assessed for 2 weeks in the study.
References:
1. Gronseth G, Cruccu G, Alksne J, et al. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7;71(15):1183-90
2. Iannone A, Baker AB, Morrell F. Dilantin in the treatment of trigeminal neuralgia. Neurology 1958; 8:126–8.
3. Braham J, Saia A. Phenytoin in the treatment of trigeminal and other neuralgias. Lancet 1960; 2:892–3.
4. Chinitz A, Seelinger DF, Greenhouse AH. Anticonvulsant therapy in trigeminal neuralgia. Am J Med Sci 1966; 252:62–7.
5. Baxter K (ed), Stockley’s Drug Interactions. [online] London: Pharmaceutical Press (accessed 21 Apr 2014); available at http://www.medicinescomplete.com. Subscription required.
6. Zakrzewska JM, Chaudhry Z, Nurmikko TJ,et al. Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain. 1997 Nov;73(2):223-30.
7. Bajwa Z, Ho C, Khan S. Trigeminal neuralgia. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 21 Apr 2017. Available from www.uptodate.com. Subscription and login required

Apr. 20, 2017Does chronic benign neutropenia cause immunosuppression and is thus an issue with receiving Zostavax. details
 

Response: Those with chronic benign neutropenia do not have an increased risk of infection.(1,5) As such, chronic benign neutropenia is not a reason to withold the Zostavax.
References: 1. UTD - Approach to the adult with unexplained neutropenia
2. UTD - Management of the adult with non-chemotherapy-induced neutropenia
3. https://www.hawaii.edu/medicine/pediatrics/pedtext/s11c08.html
4. http://asheducationbook.hematologylibrary.org/content/2012/1/174.full
5. http://www.clinicaladvisor.com/critical-care-medicine/neutropenia/article/586570/

Apr. 20, 2017Have you seen anyone having trouble with discontinuing Cymbalta being switched to fluoxetine? details
 

Response: Discontinuation syndrome of antidepressants is typically inversely related to half-life.(3) Compared to other SSRIs and SNRIs, duloxetine has a relatively short half-life at 8-19 hours.(1,2) For someone having trouble tapering, switching to fluoxetine is a viable management strategy.(2,4)
References: 1. Lexicomp
2. Clinical Handbook of Psychotropic Drugs
3. Canadian Pharmacist's Letter; March 2016; Vol: 32
4. Kelly K, Posternak M, Jonathan EA. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-418. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181894/

Apr. 20, 2017Can topical tretinoin be used three times weekly for molluscum contagiosum in children? details
 

Medication History: 5% KOH and 0.05% tretinoin similar lesion clearance at 4 weeks
Small RCT without blinding (n=50)
Tx's applied HS over lesions.
Mean lesions at baseline: 9.48 vs. 8.35 (ns) (KOH vs. tret)
At 4 weeks: 1.47 vs. 2 (ns) (KOH vs. tret)
erythema in almost all, erosion in 31% KOH vs. 19% tret; burning about 20% all; edema 26% vs 0%; itching 16% vs. 31%
(7)
Response: Treatments for molluscum in immunocompetent children with the most evidence include:
- no treatmet(1,2)
-curettage(1,2)
-cantharidin(1,2)
Treatments with limited evidence of benefit include the potassium hydroxide, salicylic gel, tretinoin cream, and several others.(1,2)
Tretinoin has been found to be as effective as potassium hydroxide when applied as 0.05% cream at bedtime for 4 weeks(7) and was less effective than 10% benzoyl peroxide when applied BID for 4 weeks.(6) An uncontrolled trial found at 12 months children who were treated for molluscum contagiosum (including 14 treated with tretinoin) had similar outcomes to those not treated.(5) Adverse effects of tretinoin include erythema, erosion, burning, and itching.(7)

Cantharidin is available from pharmacies as the brand name Canthacur®. It is applied with the blunt end of cotton swab to lesion only in the office. Application is painless and does not cause bleeding. The area can be washed with soap and water within 2-6 hours. The agent causes small blisters at the lesion site. If lesions persist, treatment can be repeated in 2-4 weeks.(1)
References: 1. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 -2017. Record No. 116448, Molluscum contagiosum; [updated 2015 Aug 20, cited 16 Mar 2017]; [about 15 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=116448&site=dynamed-live&scope=site. Registration and login required.
2. UTD - Molluscum contagiosum
3. Short K, Fuller C, Higgins M. Double-Blind, Randomized, Placebo-Controlled Trial of the Use of Topical 10% Potassium Hydroxide Solution in the Treatment of Molluscum Contagiosum. Pediatr Dermatol 2006 May-Jun;23(3):279
4. CTMA - Viral Skin Infections: Common and Flat Warts
5. Pediatr Dermatol. 2015 May-Jun;32(3):353-7. doi: 10.1111/pde.12504. Epub 2015 Jan 30. Molluscum contagiosum: to treat or not to treat? Experience with 170 children in an outpatient clinic setting in the northeastern United States. Basdag H1, Rainer BM1, Cohen BA1.
6. 10th World Congress on Pediatric Dermatology meeting abstract (Pediatric Dermatology 2004;21(3):399) as referenced in Cochrane review (Cochrane Database Syst Rev 2009 Oct 7;(4):CD004767)
7. Kathmandu Univ Med J (KUMJ). 2011 Oct-Dec;9(36):291-4. Comparative study of 5 % potassium hydroxide solution versus 0.05% tretinoin cream for Molluscum Contagiosum in children. Rajouria EA1, Amatya A, Karn D.

Apr. 21, 2017Can you provide a compounding recipe for a fluconazole suspension? details
 

Response: Fluconazole has a solubility in water of 8 - 10mg per mL and is also soluble in ethanol. The injection is usually formulated in 0.9% Sodium Chloride and has a pH of 4 - 8.
Fluconazole oral liquid is available in some countries. For small doses the injection can be given orally. Unit doses can be packed into oral syringes.

Yamreudeewong et al (1)1 prepared a 1mg per mL oral liquid by triturating Diflucan® tablets with deionised water. This preparation is chemically stable for 15 days at 4 and 23°C in glass vials. The potential for microbial growth was not assessed.
Sterile water should be used for this preparation and a 7 day expiry date is suggested.
Compatibility with flavours and syrups has not been assessed so a simple solution should be prepared as above. Flavour can be added to the dose just prior to administration. Refrigeration is important as an antimicrobial preservative is not included in the preparation.
(1)
References: 1. http://www.pharminfotech.co.nz/manual/Formulation/mixtures/fluconazole.html
*AHS Compounding manual

Apr. 21, 2017Are community pharmacies able to administer the yellow fever vaccine? details
 

Response: According to the Public Health Agency of Canada website, you must be a designated Yellow Fever Vaccination Center to aquire the vaccine. For more information on becoming a designated center please see the Public Health Agency of Canada website (1).
References: 1. http://www.phac-aspc.gc.ca/tmp-pmv/yf-fj/pro-eng.php

Apr. 21, 2017We have a patient with pruritus due to liver failure. I would like to use sertraline but it seems it's place in therapy is after standard treatments have failed, which include cholestyramine, rifampicin, naltrexone. Can you put together a list of pros and cons for these agents? For instance rifampicin may not even be available. I found out naltrexone would cost $230/30 tablets and client could not afford that. If evidence is overwhelming to use these agents first, that is what we'll do. I just want to make a recommendation to the MD. details
 

Medical Problems: liver ca
poor renal function
liver failure
Response: Pros and Cons of Cholestyramine, Naltrexone, Rifampicin and Sertraline for pruritus:

Cholestyramine:
-Is an effective first-line agent because of a favorable safety profile and extensive use.
-Overall, there have been few randomized trials of cholestyramine for cholestasis-associated pruritus. (5) Its use is not supported by overwhelming evidence as there are only two trials and they included 18 patients total. (11, 2).
-The effective dose of cholestyramine ranges from 4 to 16 grams per day, divided QID. Dosing can start as 30-60 minutes before breakfast and 30-60 minutes after breakfast. I’m not sure what is easier to accommodate; if it’s easier to get a nurse there after 2 meals, I would change this to 30-60 minutes after breakfast and lunch. The rationale to the 2 doses surrounding breakfast is that in patients with an intact gallbladder, this dosing may enhance the excretion of the pruritogens, which presumably accumulate in the gallbladder during the overnight fast.(12) Of course, any other drugs need to be separated by 4-6 hours. Medication adherence can be a significant problem as cholestyramine can be unpalatable, and induce constipation.

Rifampin (rifampicin)
— More evidence, but still very limited: 61 patients have been evaluated among 3 RCTs and 2 randomized crossover trials. (11) Several reports have demonstrated improvement in cholestatic pruritus with rifampin (5, 7, 8]. In a meta-analysis of five randomized crossover trials with 61 patients, during treatment with rifampin, 47 patients (77 percent) reported complete or partial resolution of pruritus, whereas 12 patients (20 percent) reported complete or partial resolution of pruritus while receiving placebo or alternative medication. (8)
-It is given as 150 to 300 mg twice daily but once daily dosing can be initiated and is more convenient. A 34 day supply is ~$45. Rifampin is EDS only for treatment of non-TB mycobacterium infections.

Naltrexone:
-Opioid antagonists- Opioid antagonists should not be used in patients with liver failure, or severe liver dysfunction (1).
Naltrexone is contraindicated in liver failure (14);
- There is somewhat more evidence, however, it combines all opioid antagonists (buprenorphine, nalmefene, naltrexone and naloxone); 173 patients have been evaluated in over 10 trials. (11)
- Adverse effects: dizziness, nausea, vomiting, headache, abdominal cramping (13)
- Certainly something to consider is this agent will not be able to be used in combination with opioids if they would be something considered in the future
- Dosing is once daily, which is convenient
- A 34-day supply ~295. (I based this on McKesson pricing and added the store mark-up and dispensing fee. The acquisition price is $233/30 tabs so perhaps that is what the pharmacist was quoting. Or, they don’t charge the extra fees.)

Sertraline (Full formulary):
-Used in pruritus refractory to standard treatment —Switching to sertraline at bedtime can be tried if other measures fail (based on the European Association for Study of Liver Disease).
— Case series and a small controlled trial have suggested a possible benefit from selective serotonin reuptake inhibitors. Evidence is based on a randomized cross-over trial of 12 patients. (11)
Sertraline (75 to 100 mg daily) was effective in a retrospective analysis of a group of patients with primary biliary cholangitis (9), and in a small randomized crossover trial of patients with pruritus due to various forms of liver disease. (10)
References: 1. Imam MH et al. Pathogenesis and management of pruritus in cholestatic liver disease. J Gastroenterol Hepatol. 2012 Jul;27(7):1150-8
2. Datta DV et al. Treatment of pruritus of obstructive jaundice with cholestyramine. Br Med J. 1963;1(5325):216
3. Kuiper et al. The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double-blind, randomized, placebo-controlled trial. Hepatology. 2010;52(4):1334
4. The pruritus of cholestasis. 2005 Dec;43(6):1078-88. Epub 2005 Oct 6.31, Wiertelak EP et al. Cholecystokinin antianalgesia: safety cues abolish morphine analgesia. Science. 1992 May;256(5058):830-3.
5. Tandon P et al. The efficacy and safety of bile Acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus. Am J Gastroenterol. 2007;102(7):1528. Epub 2007 Mar 31.
6. Bunchorntavakul C, Reddy KR. Pruritus in chronic cholestatic liver disease. Clin Liver Dis. 2012 May;16(2):331-46.
7. Podesta A et al. Treatment of pruritus of primary biliary cirrhosis with rifampin. Dig Dis Sci. 1991;36(2):216.
8. Khurana S, Singh P. Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials. Liver Int. 2006 Oct;26(8):943-
9. Browning J et al. Long-term efficacy of sertraline as a treatment for cholestatic pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol. 2003;98(12):2736.
10. Mayo MJ et al. Sertraline as a first-line treatment for cholestatic pruritus. Hepatology. 2007;45(3):666
11. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - 2017. Record No. 906262, Cholestatic pruritus; [updated 2016 Aug 25, cited 24 Apr 2017]; [about 11 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=906262&site=dynamed-live&scope=site. Registration and login required.UTD
12. RxTx - CTC:from CPhA
RxTx[Internet]. Ottawa (ON): Canadian Pharmacists Association; 2016. Chronic Liver Diseases; [cited April 24/17].Available from: https://www.e-therapeutics.ca/.
13. PM - ReVia

Apr. 21, 2017What is the maximum volume of a medication that can be given rectally? details
 

Response: While there appears to be no specific data, articles on rectal administration of liquids (1-3,5) have been citing a 1991 article suggesting 10-25 ml can be retained without difficulty.(4) Another suggests keeping volumes under 60 ml prevents spontaneous expulsion.(5)
References: 1. Palliative Care Formulary 5
2. PL. Detail-Document, Giving Meds by Alternative Routes. Pharmacist's Letter/Prescriber's Letter. February 2015.
3. Davis MP, Walsh D, LeGrand SB, et al. Symptom control in cancer patients: the clinical pharmacology and therapeutic role of suppositories and rectal suspensions. Support Care Cancer. 2002 Mar;10(2):117-38. Epub 2001 Nov 9. PMID 11862502
4. van Hoogdalem E, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs. Clin
Pharmacokinet. 1991;21(1):11–26
5. Warren DE. Practical use of rectal medications in palliative care. J Pain Symptom Manage. 1996 Jun;11(6):378-87. PMID 8935142

Apr. 24, 2017Can Ketorolac be used safely / effectiveinly in the neurosurgical population? details
 

Response: •There are no trials
• Most papers I read don’t include NSAIDs in the discussion of SAH-induced headache recommended managemet (2-4) and one paper recommended against NSAIDs post-SAH. (5)
• One paper had a discussion of pain management for headaches; the discussion of headache following SAH did not include NSIDs. (6) However, it listed ketorolac and diclofenac in the table as treatment options for postoperative headaches and SAH. The references for this were:
i. a retrospective stud (7) of gabapentin for SAH headache management in which ‘other common analgesics were mainly acetaminophen and occasionally ketorolac’ is the only mention of ketorolac; the lead author of the study (7) is also lead author of the review.(6)
ii. a review of pain management following intracranial surgry (4) This paper does mention NSAIDs in the discussion of nonopioid analgesics and does include ketorolac in the dosing table; however, the authors do not include NSAIDs in the recommendations section.
References: 1. Effects of nonsteroidal anti-inflammatory drugs on hemostasis in patients with aneurysmal subarachnoid hemorrhage. Niemi T, Tanskanen P, Taxell C, Juvela S, Randell T, Rosenberg P. J Neurosurg Anesthesiol. 1999 Jul;11(3):188-94. PMID: 10414674
2. Effect of nonsteroid anti-inflammatory drugs on subarachnoid hemorrhage in dogs. White RP, Hagen AA, Robertson JT. J Neurosurg. 1979 Aug;51(2):164-71. PMID: 582181
3. Glisic E, gariner L, Josti L, et al. Inadequacy of Headache Management After Subarachnoid Hemorrhage. Am J Crit Care. 2016;25(2):136-143. Accessed at http://www.medscape.com/viewarticle/861069_5
4. Ravishankar K, Chakravarty A, Chowdhury D, et al. Guidelines on the diagnosis and the current management of headache and related disorders. Ann Indian Acad Neurol. 2011;14(Suppl1):S40-S59. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152170/
5. http://vip.regionh.dk/VIP/Redaktoer/1301XC.nsf/vLookupUpload/ATTACH-RHAP-8X2FLV/$FILE/SAH%20Hemorrhage%20-%20A%20Guideline%20for%20Healthcare%20Professionals%20From%20the%20American%20Heart%20Association%20-%20American%20Stroke%20Association.pdf
6. Dhakal, L.P., Harriott, A.M., Capobianco, D.J., et al. Headache and Its Approach in Today’s NeuroIntensive Care Unit. Neurocritical Care. 2016; 25(2):320-334. (from SCOPUS)
7. Petzold, A., Girbes, A. Pain management in neurocritical care. Neurocrit Care. 2013; 19(2): 232-256 (from Scopus)
8. Friedman, B.W., Lipton, R.B. Headache emergencies: Diagnosis and management. Neurol Clinics. 2012; 30(1): 44-59
9. Dhakal LP, Hodge DO, Nagel J, et al. Safety and tolerability of gabapentin for aneurysmal subarachnoid hemorrhage (sah) headache and meningismus. Neurocrit Care. 2015;22:414–21.
10. Gottschalk A, Yaster M. The perioperative management of pain from intracranial surgery. Neurocrit Care. 2009;10:387–402.
11. Parkhutik V, Lago A, Tembl JI,et al. Influence of COX-inhibiting analgesics on the platelet function of patients with subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2012 Nov;21(8):755-9. doi: 10.1016/j.jstrokecerebrovasdis.2011.04.002. Epub 2011 May 6. PMID 21550266
*Trip

Apr. 24, 2017The nurses from the mines up north are asking for naloxone kits (we send them naloxone vials). Is there a special program for this? details
 

Response: Kits can be ordered from the Control Group for $31 each.(1) They have a phone number on their order form that can be called for information about current stock.(2)
References: 1. https://www.skpharmacists.ca/pharmacists/resources/naloxone
2. https://docs.google.com/forms/d/e/1FAIpQLSdVBaFjk-gvjmRWO09XWNf47MLp7Uifm3dF8ZAV_iUC-CX9cQ/viewform?c=0&w=1

Apr. 24, 2017A product called Sleep Harmony (NPN 80063986) seems to just contain lavendar but it says it's active ingredient is Silexan, a patented lavendar oil. Are there any drug interactions with Silexan? details
 

Response: Silexan is simply a patented ingredient that only contains lavendar(1-3), such that interactions only apply to lavendar. Lavendar should be used with caution in people on antihypertensives as it may have additive hypotensive effects and in people already taking CNS depressants, especially barbiturates, benzodiazepines, and chloral hydrate.(3)
References: 1. http://www.sleepharmony.ca/product-information
2. http://www.sleepharmony.ca/about
3. Natural Medicines

Apr. 24, 2017Would restasis eye drops be an issue for someone receiving the Zostavax vaccine? details
 

Response: Cyclosporine A, when applied ophthalmically twice daily, is not quantifiable in the blood even after 12 months' use.(1) Considering this means the concentration is at least 6550 times lower than those measured during systemic therapy for non-life-threatening indications, there is no concern of immunosuppression and this patient can receive Zostavax.
References: 1. eCPS - Restasis

Apr. 24, 2017Is there any evidence out there comparing IV to oral ketamine when it comes to efficacy for acute pain? details
 

Response: Overall, there is limited evidence for using oral Ketamine for acute pain. Of note, oral ketamine for acute pain is an off-label use. (1)
One limiting factor for the use of ketamine for acute pain may be the onset of action. While IV ketamine has an onset of action of 1-5 minutes, oral ketamine has an onset of 30 minutes. Oral bioavailability of ketamine ranges from 16-30% (and is highly variable due to extensive first pass hepatic metabolism). (2)
References: 1.CPS Monograph- ketamine
2. I.S. Grant, W.S. Nimmo, J.A. ClementsPharmacokinetics and analgesic effects of i.m. and oral ketamine. Brit J Anaesth 53 1981 805–810.
3. Robert A. Schoevers, Tharcila V. Chaves, Sonya M. Balukova, Marije aan het Rot, Rudie Kortekaas. The British Journal of Psychiatry Feb 2016, 208 (2) 108-113
4. Maren Blonk et al. Use of oral ketamine in chronic pain management: A review. European Journal of Pain. Volume 14, Issue 5; May 2010: 466–472.
5. J.R. Holtman Jr., P.A. Crooks, J.K. Johnson-Hardy, M. Hojomat, M. Kleven, E.P. Wala Effects of norketamine enantiomers in rodent models of persistent pain. Pharmacol Biochem Behav 90 2008676–685.
6. T. Rabben, P. Skjelbred, I. Oye Prolonged analgesic effect of ketamine, an N-methyl-d-aspartate receptor inhibitor, in patients with chronic pain.J Pharmacol Exp Ther 2891999 1060–1066.

Apr. 24, 2017How much calcium is in the "atorvastatin calcium" tablets? details
 

Response: The amount of calcium in an 80 mg tablet of Lipitor (regardless of brand) on account of the atorvastatin calcium is 2.65 mg.(1) The amount in a 10 mg tablet is 0.33 mg.(1) Some brands also contain calcium carbonate in the non-medicinal ingredients.(3) An 80 mg tablet, including the drug and the non-medicinal ingredients would not likely be more than ~ 200 mg. There are 13 other non-medicinal ingredients in a Lipitor tablet, but for the sake of argument, let’s say 120 mg of the tablet (200 mg total tablet size – 80 mg atorvastatin calcium) is calcium carbonate; since calcium carbonate is 40% elemental calcium(4), this would add an additional 48 mg. However, as pointed out above, this is a gross overestimation and one should not rely on atorvastatin tablets as a source of calcium.
References: 1. Martindale
2. http://www.ptable.com/
3. eCPS - Lipitor
4. eCPS - CPhA Calcium salts

Apr. 25, 2017What would be equivalent to Concerta 72mg per day? The patient cannot afford this. details
 

Patient Age: 29
Patient Sex: M
Medication History: Abilify 2mg
Cipralex
Response: 1. 72mg concerta is approximately equal to methylphenidate IR 40-60mg (1-5), with no established SR recommendation. Concerta 54mg is equivalent to methylphenidate SR 60mg daily (20-40 qam, then 20-40mg around 2pm). That would be a reasonable starting point, and another 20mg could be added QAM or QPM in 7 days if not satisfactory response (100mg max dosage CADDRA).

2. Biphentin could also be tried, but would cost similar to concerta at the dose required.
References: 1. Monographs
2. Lexi
3.PL Detail-Document, Comparison of ADHD Medications. Pharmacist’s Letter/Prescriber’s Letter. March 2016.
4. https://www.caddra.ca/pdfs/caddraGuidelines2011Chapter07.pdf
5. Handbook of Psychotropic Drugs, 20th edition

Apr. 25, 2017Bilaxten (Bilastine) is being dosed at 80mg once daily -- is there evidence to support such a high dose for urticaria? details
 

Patient Age: 31
Patient Sex: F
Medical Problems: Urticaria, continual
Response: 1. Only one study in humans with doses of 80mg could be found (1). This study (2) tested placebo, 20, 40, or 80mg doses in a crossover design for 7 days in cold-contact urticaria. Increasing efficacy found with increasing doses. No safety issues different than placebo. Could not find long-term studies for high doses like this.
References: 1. medline search, BILASTINE
2.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759706/
3. https://link.springer.com/article/10.1007%2Fs40261-016-0447-2

Apr. 26, 2017 I have a diabetic patient with asthma who has developed dry cough and worsening dypsnea post-MI. I suspect the ACE-inhibitor and beta blocker as potential causes. Is there any evidence for switching them? details
 

Patient Age: 65
Medical Problems: #Deleted
Medication History: #Deleted
Response: ARBs are proven to be effective options post-MI if ACE inhibitors are indicated but not tolerated. Valsartan (post-MI target 160 mg BID) from VALIANT trial and candesartan (32 mg daily post-MI target) from CHARM trial have evidence of being effective alternatives to ACE inhibitors post MI. (1,2,3,4,5) Note: The ramipril 10 mg daily dose that your patient is on was the post-MI target dose for ramipril.

Cardioselective beta blockers are preferred post-MI for those with asthma and DM (the cardioselective beta blocker acebutolol with intrinsic sympathomimetic activity less benefit). So we are left with metoprolol, bisoprolol, and atenolol as preferred options in these patients at cardioselective doses. (6,7) Metoprolol 100 mg BID is the target dose for post-MI. (8) 200 mg daily of metoprolol is also the maximum dose in which metoprolol can retain its cardioselectivity. (9) Therefore, the metoprolol 50 mg BID dose that your patient is on is a reasonable dose for a diabetic with asthma, and in fact he could potentially be titrated to the post-MI target dose of 100 mg BID if tolerated. (1)
References: 1. Jensen B, Reiger L. Post-Myocardial Infarction: Drug and Dosage considerations. RxFiles 11th edition. Updated March 2017.
2. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan in Acute Myocardial Infarction Trial Investigators (VALIANT). Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003 Nov 13;349(20):1893-906.
3. McMurray J, et al. The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). J Am Coll Cardiol. 2006 Feb 21;47(4):726-33.
4. Granger CB, McMurray JJ, Yusuf S, et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003 Sep 6;362(9386):772-6.
5. McMurray JJ, Ostergren J, Swedberg K,et al.; CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003 Sep 6;362(9386):767-71.
6. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of st-elevation myocardial infarction. (STEMI) A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2012.
7. Which Beta-blocker. Med Lett 2001;43:9-11. & Drugs for Hypertension, Treatment Guidelines from the Medical Letter 2003; Vol 1 (Issue 6) 33-40.
8. Janosi A, Ghali JK, Herlitz J, et al.; MERIT-HF Study Group. Metoprolol CR/XL in postmyocardial infarction patients with chronic heart failure: experiences from MERIT-HF. Am Heart J. 2003 Oct;146(4):721-8.
9. Shelley R. Salpete. Cardioselective Beta Blocker Use in Patients With Asthma and Chronic Obstructive Pulmonary Disease: An Evidence-Based Approach to Standards of Care. Cardiovasc Rev Rep. 2003;24(11).

Apr. 26, 2017I want to give client azithromycin and he currently takes lamotrigine and has an allergy to sulfonamides. Is this a problem? details
 

Response: There are no interactions(1,2) and azithromycin is not related to sulfonamide antibiotics(3) so the client can safely receive the azithromycin.
References: 1. Stockley's
2. Lexicomp
3. Lexicomp - Sulfonamide Antibiotic Allergy

Apr. 26, 2017For the HbA1c blood test, could anything falsely change the results? details
 

Response: There are several potential factors that can affect HbA1c results; certainly anything that affects erythrocytes or hemoglobin can affect HbA1c.(1-7) Clinical significance in a general sense was not found. There are several case reports of unexplainable HbA1c results that the authors have traced to a particular interfering factor.(6) However, I suspect the clinical significance is very individual, possibly because of the spectrums of the severity of interfering conditions. The type of assay used can be a variable for some of the factors, but not all.(3,5,6) Most of the cases were identified because the HbA1c was inconsistent with daily blood glucose results; for instance, in one case the HbA1c of a patient on dapsone declined to 3.7% over several years despite the fact his blood glucose was uncontrolled.(8)

One article that is quite comprehensive.(7) It was published in 2009 though seemingly all that may have changed since then are the assays used. This article goes through all the different identified drugs and conditions that may affect HbA1c results, including iron deficiency and use of erythropoietin; it has a short paragraph on the complicated relationship between HbA1c and CKD.
It seems the only way to really know if something might be interfering with the assay is to compare assay results to the blood glucose levels. In patients whose HbA1c is not in line with their blood glucose levels, the only suggestions I found were to rely only on blood glucose levels or check fructosamine.(5) Fructosamine is available through the SK Disease Control Lab(9), though I don’t have any other information such as cost, proper application of the results, limitations of patient eligibility, etc.
References: 1. http://medsask.usask.ca/professional/Common-lab-tests-guide/index.php - Diabetes
2. http://guidelines.diabetes.ca/Browse/Chapter9#tbl1
3. https://www.aacc.org/~/media/practice-guidelines/diabetes-mellitus/diabetesmellitusentirelmpg.pdf?la=en
4. http://www.ngsp.org/interf.asp
5. HbA1c and monitoring glycaemia. Aust Fam Phys 2012; 41(1):37-40 http://www.racgp.org.au/afp/2012/januaryfebruary/hba1c-and-monitoring-glycaemia/
6. Unnikrishnan R, Anjana RM, Mohan V. Drugs affecting HbA1c levels. Indian J Endocrinol Metab. 2012;16(4):528-531. doi:10.4103/2230-8210.98004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401751/#!po=30.0000
7. Gallagher E, Le Roith D, Bloomgarden Z. Review of hemoglobin A1c in the management of diabetes. J Diabetes. 2009;1(1):9-17
Possibly accessible via http://onlinelibrary.wiley.com/doi/10.1111/j.1753-0407.2009.00009.x/abstract
8. Kesson CM, Whitelaw JW, Ireland JT. Drug-induced haemolysis and fast haemoglobin A1 in diabetes mellitus. Br Med J. 1979;2:1037–8. (Case report referenced in [6])
9. http://sdcl-testviewer.ehealthsask.ca/Home/Details?id=365

Apr. 26, 2017I have been getting lots of questions about Repatha and Praluent. Can these be used in patients that are intolerant to statins? The monographs indicate that they are adjuncts to maximum statin therapy. Is there a good resource other than the monographs to read more about the use of alternative therapies for LDL reduction? details
 

Response: Alirocumab (Praluent) and evolocumab (Repatha) may be used in patients with uncontrolled familial hypercholesterolemia or those with athersclerotic cardiovascular disease (primary hyperlipidemia).(7) It seems likely this drug would have application to a broad population of patients who don't tolerate other antihyperlipidemics, especially statins, and indeed these patients were included in trials.(3) However, the reliance of surrogate markers (LDL) for demonstration of effectiveness and lack of long-term safety data present obstacles to uptake.(2,3) The most significant obstacle is the price: these agents are >$600 per month acquisition cost.(7) The Common Drug Review (CDR) recommended against listing evolocumab for primary hyperlidemia.(5) While a recommendation was made in favour of alirocumab for primary hyperlipidemia, this was under the condition the price be reduced by 57%.(6) Currently neither drug is listed as a benefit for any indication so will only be used in patients who are willing to pay the out-of-pocket cost.(8)
It is thought that 90% of patients who report statin intolerance are able to continue statins after a step-by-step approach(9). The RxFiles has a great document of managing statin inolerance.(10)
References: 1. CTC - Dyslipidemias Ghislaine O. Roederer, MD, PhD Date of Revision: June 2016
2. https://www.cadth.ca/dv/pcsk9-inhibitor-monoclonal-antibodies-treatment-hypercholesterolemia
3. http://www.cjhp-online.ca/index.php/cjhp/article/viewFile/1580/2387
4. Sask formulary online
5. http://www.fhcanada.net/wp-content/uploads/2016/10/PCSK9_Repatha_Evolocumab_Common_Drug_Review.pdf
6. http://www.fhcanada.net/wp-content/uploads/2016/10/PCSK9_Praluent_Alirocumab_Common_Drug_Review.pdf
7. RxTx - eCPS - respective monographs
8. PharmaClik
9. http://www.acc.org/latest-in-cardiology/articles/2015/08/11/09/16/statin-intolerance-not-a-myth
10. http://www.rxfiles.ca/rxfiles/uploads/documents/Lipid-Statin-Intolerance.pdf

Apr. 26, 2017I have a patient on warfarin going in for cataract surgery. Does she need to discontinue? The surgeon said it was up to me. details
 

Patient Age: 87
Patient Sex: F
Medical Problems: A fib, regular
HTN - controlled
asthma
CHAD2 S2-Vasc = 4; HAS-BLED = 2 (2)
Response: Cataract surgery carries a standard risk of bleeding.(1) While the patient's thromboembolic risk is high based on CHAD2S2-Vasc score, because the bleed risk is standard, no interruption in warfarin therapy is required.(1)
References: 1. http://medsask.usask.ca/documents/newsletters/33.2%20Periprocedural%20Antithrombotics.pdf
2. http://sparctool.com/

Apr. 27, 2017Is leflunomide truly contraindicated in chronic kidney disease patients? The monograph says it is, but there does not seem to be substatianting evidence for this. details
 

Patient Age: 83
Patient Sex: F
Medical Problems: 100 lb
GFR 26 (stage 4 CKD)
-rheumatoid arthritis
Medication History: Replavite B&C - 1 od
Metoprolol 50mg 1 bid
Vitamin D 2000IU once daily
Simvastatin 40mg 1 hs
Ramipril/HCTZ 10/12.5mg 1 od
Hydroxychloroquine 200mg 1.5 tabs once daily
Response: The very unsatisfying reason for the contraindication is insufficient study of leflunomide in CKD patients.(1-4) Like you, I struggle to understand the seemingly extreme precaution; certainly some inactive metabolites are excreted renally but the active metabolite is not excreted unchanged.(1) Two pieces of information lead me to believe a contraindication is unjustified:
1. Aubagio (teriflunomide = active metabolite of leflunomid[9]) has no contraindication nor dose adjustment requirement in CKD according to the monograph. In fact, the monograph states: “Severe renal impairment had no impact on the pharmacokinetics of teriflunomide. No dosage adjustment is necessary for patients with severe renal impairment.” (1) Considering leflunomide is essentially teriflunomide, it makes no sense that the two differ in terms of this recommendation.
2. The kinetics of leflunomide of five patients on hemodialysis were determined and found that removal of teriflunome was negligible (9). This patient is not on dialysis but this indicates to me patients with no renal function (either natural or renal replacement, since it did not remove the drug) are able to take leflunomide. It is important to mention this paper was strictly addressing the kinetics and made no mention of adverse effects or complications of using leflunomide in these patients. However, their data were collected between 2005 and 2010, which suggests to me they did not have problems with the drug in this population. Of course five patients is a small number.
Should the patient take the drug and experience severe adverse effects, one could also consider the availability of activated charcoal/cholestyramine for enhanced removal of leflunomide reassuring.
Considering the high protein binding of leflunomide (99.3%), it would be prudent to ensure the patient has adequate serum albumin levels.
References: 1. eCPS - respective monographs
2. Renal Drug Handbook 2010
3. AHFS
4. https://www.medicines.org.uk/emc/medicine/24155
5. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000235/WC500026289.pdf
6. http://www.medsafe.govt.nz/profs/Datasheet/a/aravatab.pdf
7. https://arthritis-research.biomedcentral.com/articles/10.1186/ar3256
8. Swarup A, Sachdeva N, Schumacher HR: Dosing of antirheumatic drugs in renal disease and dialysis. J Clin Rheumatol. 2004, 10: 190-204. PMID 17043508
9. Clin Rheumatol. 2013 Feb;32(2):267-70. doi: 10.1007/s10067-012-2122-1. Epub 2012 Nov 22. Leflunomide in dialysis patients with rheumatoid arthritis--a pharmacokinetic study.
Bergner R1, Peters L, Schmitt V, et al. PMID: 23179005

Apr. 27, 2017Is there established efficacy for Differin use in an 8 year old? details
 

Patient Age: 8
Patient Sex: M
Medical Problems: ?Acne?
Medication History: Adapalene
No other medications filled recently
Response: Assumption is that this is treating acne. Entry to market studies excluded children under the age of 12, so only post marketing data exists. Of this, the FDA has outlined ten's of serious adverse events, but no deaths attributable to adapalene. There is no evidence to suggest that it is safe to use in an 8 year old, but adapalene is poorly absorbed, and is also unlikely to cause a theoretical risk. Regardless, discuss side effects with the caregiver, and consider contacting the doctor for an alternate product if there are concerns surrounding the use of this product.
References: 1. UpToDate - Adapalene
2. FDA - Pediatric advisory committee - Adapalene

Apr. 28, 2017Can you comment about this red box / blue box "Xyngular" product? details
 

Response: I can’t provide you with a complete review of this product. The main reason is the way the manufacturer lists the ingredients, it is impossible to know the dosages of any one ingredient; secondly, there are just so many ingredients it would take a week and I know my response will be the same: there is no evidence to support claims; one cannot be sure the product contains what is listed (and more importantly does not contain undeclared ingredients such as stimulants).

As for the dosages, all of the products are listed as ‘proprietary blends’. As an example, it would be like taking a combination cold and flu product and listing like this:
ColdBeGone proprietary blend 3850 mg
acetaminophen, brompheniramine, dextromethorphan, guaifenesin
Clearly that’s not very helpful!

There are a lot of sources of caffeine in the product (denoted with an asterisk in the ingredients below) which is typical for weight loss products. Because we don’t know the amount of each individual ingredient, it is impossible to know how much caffeine would be consumed over the course of a day. One of the products also contains bitter orange, which has stimulant properties, which again, if the dose is unknown, can be potentially dangerous. Also, typical of weight loss products are laxatives, which are found in Flush. So people lose water weight and feel good about themselves.

This is what is in the blue box:

New Global Blend
We recommend taking 1-2 ounces of Global Blend at your convenience without food.
Proprietary Hi Orac Blend 6400 mg
several fruits and extracts, green tea extract*, sea buckthorn, grape seed extract, raspberry seed extract, white leaf tea*, aloe vera juice concentrate (from 1 mg 200:1 concentrate), goji berry, noni fruit, mangosteen
Proprietary Adaptagen Blend 50 mg
Amia fruit, panax ginseng root extract, eleuthero root
Proprietary Primary 30 mg
antioxidant complex - l-glutamic acid, l-cysteine, glycine

Accelerate
We recommend taking 2 accelerate mid-afternoon with food
Propietary Blend 850 mg
Green tea leaf*, guarana seed extract*, oolong tea extract*, kola nut extract*, cayenne pepper

Axion
We recommend taking 2 Axion first thing in the morning with food.
vitamins/minerals,
inositol 12.5 mg, lycopene 2 mg, lutein 5 mg, ALA 12.5 mg, quercetin 25 mg, CoQ10 12.5 mg, flaxseed 50 mg, bromelain 25 mg, papain 12.5 mg, pepsin 12.5 mg, spirulina 50 mg, resveratrol 5 mg, green tea leaf extract* 30 mg, rhodiola root extract 10 mg, panax ginseng root extract 10 mg, probiotics

Cheat+
We recommend taking Cheat+ 30 minutes before a meal. Always consume a minimum of 8oz of water when taking Cheat+.
Proprietary Blend 1230 mg
glucomannan, green coffee bean extract*, phytosterols, hydroxypropyl cellulose

Flush
We recommend consuming 2 flush before sleep on an as empty stomach
Proprietary blend 1300 mg
senna leaf powder, cinnamon bark, psyllium husk powder, fenugreek, clove, garlic bulb, aloe vera, ginger root, dandelion, slippery elm bark

Lean
We recommend consuming 1 scoop of lean with your choice of beverage, as outlined in the program you are utilizing.
More vits/minerals/fruit extracts/enzymes
Amino acid proprietary blend
alanine, arginine, aspartic acid, cystine, glutamic acid, glycine, histidine, isoleucine, lysine, methionine, phenyllalanine, proline, serine, threonine, taurine, tryptophan, tyrosine, valine
Lean Propietary bledn 13.4 g
soy isolates, soy milk, whey isolates, whey concentrates

Spryng
We recommend consuming Spryng on an empty stomach before or during exercise or another challenging event that requires mental and physical energy. (= energy/sports drink)
some vitamins
Proprietary blend 7, 138 mg
palatinose, l-citrulline, l-glutamine, ElevATP ancient peat and apple extract, ashwaganda root, alpha GPC, CoQ10, lycium berry 10:1 extract, cordyceps

Xyng
We recommend consuming 1 capsule of Xyng with food, no later than 3pm. If Xyng is well tolerated then it can be consumed on an empty stomach.
Proprietary Blend 733 mg
caffeine anhydrous*, white willow bark, 5-HTP, bitter orange extract, 30% synephrine alkaloids, garcinia cambogia - 60% hydroxycitric acid, green tea leaf extract*, cayenne pepper, rhodiola, korean ginseng root, maca root, black tea leaf extract*, yohimbe, undaria, black pepper

XR2
We recommend consuming 2 tablets on an empty stomach as needed to combat stress, stress eating, and improve sleep.
Proprietary Blend 670 mg
magnolia bark, phellodendron, valerian root, l-theanine, GABA, 5-HTP, celery seed

Xypstix
We recommend using 1 stick at your convenience without food.
Proprietary blend 550 mg
fruit extracts, acai fruit, goji berry, noni fruit, green tea leaf*, seabuckthorn fruit extract, white tea leaf*
Proprietary antioxidant blend 10 mg
l-glutamic acid, l-cystine, glycine, melon extract
Proprietary adaptagen blend 2000 mg
aloe vera juice, amla fruit extract, panax ginseng root, eleuthero root
References: 1. http://www.xyngular.com/en/products/faq-xypstix/
2. Natural medicines