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Podcasts by pharmacists for pharmacists

5 TIPS FOR BETTER INHALER ADHERENCE Optimal timing for antibiotic therapy

“The healthcare system is changing, and pharmacies can and should play a bigger role in shaping that change.” —Michael Do MedEssist



Thank you for your sacrifice during this crisis It’s no easy task to sacrifice your own wellbeing to protect that of your community. At Teva Canada, we are so thankful that we can trust heroes like you to fight on the frontlines of the COVID-19 crisis. And it’s our promise to support you in your essential work.

We’re here for you and together we will get through this.


Contents NOVEMBER 2020 [VOL.7 NO.9]






The mental health toll of COVID-19 / BY VICKI WOOD

This month: Readers share their tips for boosting morale in the pharmacy


A review of new launches, new indications, new dosage forms, discontinued drugs and Health Canada Advisories / BY LU-ANN MURDOCH





25 32 35 38

Therapeutic Issues Adverse Reactions




Enhancing adherence to inhaler therapy / BY SARA INGRAM


Timing is everything: Understanding the optimal duration of antibiotic therapy for common infections / BY SUZANNE SINGH


Tooth be told: Combogesic may change dental pain management / BY NARDINE NAKHLA



“B” healthy: Vitamin B12 deficiency in recurring aphthous ulcers / BY ANDREW SAVO


Innovator Profile: Michael Do—Empowering pharmacists, one app at a time



42 45 46



Are you listening yet? Check out these podcasts / BY ROSALIND STEFANAC


Employment opportunities and services


Strategy: How to plan for pharmacy automation / BY PAVITHRA RAVI



www.CanadianHealthcareNetwork.ca /


@PharmacyPracticePlusBusiness [Vol.7 No.9] NOVEMBER 2020




SUGAR-FREE: Sweetened with Stevia COLOURED NATURALLY WITH: Turmeric & Paprika Extract SAME PSYLLIUM HUSK MULTI-HEALTH BENEFITS • Regulates bowels* • Lowers cholesterol levels† • Temporarily suppresses appetite§ Above benefits apply to Metamucil Powder variants only

Scan the QR code to learn the Science Behind Metamucil *By relieving irregularity; †Lowers mildly to moderately elevated cholesterol levels when taken with a low-fat diet; §When taken prior to a meal; ‡Among recommendations in ProVoice™ surveys 2015 to 2020 (OTC Bulk Fibre category).

Editor’s Message




Flu vaccine time is always a high-stress period for pharmacists, but this year it’s accompanied by the quadruple whammy of super-charged vaccine promotion campaigns from public health; first-time (but limited) pharmacy availability of the high-dose flu vaccine for seniors; sporadic, phased-in delivery of vaccine supplies; and the new reality of social distancing and PPE requirements. No wonder the comments on CanadianHealthcareNetwork and ‘pharmacy Twitter’ are flooded with pharmacists venting about their stress levels right now. Here’s a sampling of the pharmacists tweets I’ve seen this week: “Every year I say this is going to be the flu season that breaks me. This year I really mean it.” “What’s the best antidepressant to cope with dreaming about flu shots, parenting without a single break for 210+ days, stressed about staff, coping with grieving husband?” “As someone who is within 2 metres of hundreds of people a day, my anxiety keeps me up at night. I always worry that I am exposing the public to COVID.” Pharmacists, we need you to stay well. Venting online can be healthy, but if you find that you can no longer adjust your own oxygen mask, there are some excellent, confidential resources especially for healthcare workers. (www.camh.ca/en/health-info/ mental-health-and-covid-19/information-for-professionals.) Please don’t wait until you can’t breathe.

I’m desperately searching for good news right now, without much luck. Total Canadian cases of COVID-19 topped 218,000 this month, Halloween is cancelled and there is snow in the forecast. My social media feeds are dominated by friends sharing the difficulties they’re having dealing with the toll of this seemingly endless pandemic. Parents are exhausted from juggling work with their restless children’s hybrid in-class and at-home schooling. Many are also monitoring the physical and mental health of elderly parents— while staying away to keep them safe. Folks are suffering from lack of human contact. The laid-off are struggling to survive; entrepreneurs who have had to shutter their businesses in hospitality or the arts are watching their life’s work evaporate. Those who have kept their jobs have seen workloads surge, with little downtime in which to recharge their batteries and acknowledge what’s happening in the world around us. But none have paid as high a toll as healthcare workers. Pharmacists were thrust into crisis mode eight months ago and after a brief semi-reprieve this summer, you’ve had to run right back onto the battlefield; this time to arm Canadians against the flu. (Not that many pharmacists have actually had a break. In Alberta and Ontario, the short-lived downturn in COVID-19 cases in late summer ushered in the launch of asymptomatic testing in some community pharmacies.)

PHARMACY PRACTICE + BUSINESS SENIOR VICE PRESIDENT, CANADA Donna Kerry dkerry@ensembleiq.com VICE PRESIDENT/ GENERAL MANAGER EVENTS Michael Cronin mcronin@ensembleiq.com EDITOR Vicki Wood vwood@ensembleiq.com




@Ppr_plus @PharmacyPracticePlusBusiness

ACCOUNT MANAGER, QUÉBEC Nancy Dumont ndumont@ensembleiq.com

CONTINUING EDUCATION/ PROJECT MANAGER/PROOFREADER Rosalind Stefanac SALES COORDINATOR Kalli Sagos SENIOR DIRECTOR, DIGITAL ksagos@ensembleiq.com CANADA & SPECIAL PROJECTS Valerie White COLUMNISTS AND CONTRIBUTING/CONSULTING SENIOR DIRECTOR EDITORS AUDIENCE STRATEGY Derek Desrosiers, BSc(Pharm), Lina Trunina RPEBC, RPh; Shelley Diamond, ltrunina@ensembleiq.com BScPhm; Sherilyn Houle, BSP, PhD; Sandra Knowles, BScPhm; BRAND DIRECTOR Lu-Ann Murdoch, BScPhm; Nardine Martin Rissin Nakhla, PharmD; Carlene Oleksyn, mrissin@ensembleiq.com BSP Pharm, CTH; Vikas Parihar, SENIOR ACCOUNT MANAGERS, BScBiochem, BScPharm, PharmD; TORONTO Jillian Reardon, BSc(Pharm), ACPR, Norman Cook PharmD, RPh; Rosalind Stefanac; ncook@ensembleiq.com Karen Welds Scott Tweed stweed@ensembleiq.com




Pharmacy Practice + Business, established in 1985, is published 10 times a year by EnsembleIQ, 20 Eglinton Ave. West, Suite 1800, Toronto, ON, M4R 1K8 Phone: 877.687.7321 Fax: 888.889.9522. Website: CanadianHealthcareNetwork.ca. Montreal Office: 2000, rue Peel, Bureau 760, Montréal, Quebec, H3A 2W5. Pharmacy Practice + Business is abstracted in International Pharmaceutical Abstracts (IPA). Subscriptions: $98.00 per year, 2 year $156.00, Outside Canada $156.00 per year, Single Copy $12.00, Groups $69.00, Outside Canada Single Copy $16.00. Pharmacy Practice + Business is published 10 times per year except for occasional combined, expanded or premium issues, which count as two subscription issues. Mail Preferences: Occasionally we make our subscriber list available to reputable companies whose products or services may be of interest to you. If you do not want your name to be made available please contact us at contactus@canadianhealthcarenetwork.ca. Contents copyright © 2020 by EnsembleIQ; may not be reprinted without permission. EnsembleIQ does not assume liability for content. Pharmacy Practice + Business receives unsolicited materials (including letters to the editor, press releases, promotional items and images) from time to time. Pharmacy Practice + Business, its affiliates and assignees may use, reproduce, publish, re-publish, distribute, store and archive such unsolicited submissions in whole or in part in any form or medium whatsoever, without compensation of any sort. ISSN 08-29-2809.

SUBSCRIPTION SERVICES To subscribe or renew, go online to www.CanadianHealthcareNetwork.ca/subscribe, phone toll-free 1.877.687.7321 between 9 a.m. to 5 p.m. EST weekdays, fax 1-888-520-3608 or email pharmacypractice@canadianhealthcarenetwork.ca CONTINUING EDUCATION All CCCEP-accredited continuing education lessons featured in Pharmacy Practice + Business are available for credit online at eCortex.ca. Use your CanadianHealthcareNetwork.ca login for easy access. Registration is free to qualified pharmacy professionals. For assistance with our CE programs, please email ecortex@canadianhealthcarenetwork.ca REPRINTS, PERMISSIONS, AND LICENSING Please contact Wright’s Media Email: ensembleiq@wrightsmedia.com Phone: 1.877.652.5295 FIND US ONLINE The online home for Pharmacy Practice + Business is CanadianHealthcareNetwork.ca. Registration is easy and free to qualified pharmacy professionals.



CONTACT US: 20 Eglinton Ave. West, Suite 1800, Toronto, ON, M4R 1K8; Phone: 1.844.694.4422; Fax: 1.844.815.0700; Email: pharmacypractice@canadianhealthcarenetwork.ca; Publications mail agreement no. 42940023.

[Vol.7 No.9] NOVEMBER 2020


Introducing NEW New patented formula, Same trusted quality.

TM †

FeraMAX® Pd (polydextrose) is a Unique Iron Formulation ation Ferric iron core is complexed with homogenous polydextrose, ensuring a more uniform molecular structure of the iron complex

New Distinctive Packaging





Fe3+ P

Proprietary Fe3+ Polysaccharide Iron Complex (PIC)



Proprietary Fe3+ Polydextrose-Iron Complex (PDIC)

Our new packaging provides the most relevant clinical information at a glance, making it easier to use and locate FeraMAX® Pd Therapeutic 150 on the shelf.

Easier product selection by pharmacist and ease of use by patient Visualconnection “what’s inside”

Consumer-friendly Visual layout provides the most relevant clinical information at a glance

New Natural Product Number (NPN)

Brand name and dose are clearly visible on the capsule, helping to identify FeraMAX® Pd Therapeutic 150 and organize patient medications easily (same once-daily dosing).

Available at all major wholesalers November 2020 New FeraMAX® Pd Therapeutic 150 is available in packs of 30 and 100 capsules. † Pharmacy Practice+ and Profession Santé 2020 / The Medical Post and Profession Santé 2020 – Data on FeraMAX® from Survey on OTC Counselling and Recommendations




More than 42,000 pharmacists are currently practising in Canada in a range of environments. That represents an enormous volume of expertise and experience that could be tapped into to help each other solve everyday problems. We thought it would be a good idea to mine that wealth of knowledge to help each other solve some common everyday problems. In each issue, we’ll share pharmacists’ tips and ideas for making life just a little easier. LAST MONTH WE ASKED:

What’s a simple thing you do in your pharmacy to boost staff morale?

“Sunday mornings before we open, I make waffles for the staff. Strawberries, whip cream, and syrup. A simple task, but it starts the day and week off right.” —Steve Bond, ON “Gratitude. Offer your staff praise and thanks. A little gesture goes a long way.” —Brittany Faubert, Sarnia, ON

“I keep a roll of gold star stickers handy and look for reasons to give them away to thank our teammates for their work/ kindness/great ideas/etc. It’s a little juvenile, but I have yet to meet someone who refuses to accept one! It’s also a little reminder to myself to stay positive and focus on the good things being accomplished in our department, big or small.” —Amanda Holgate, Abbotsford, BC

“At our pharmacy, recognition of going above-and-beyond, for learning new tasks, recognition of hard work on a difficult or challenging day, and showing initiative is key. Settling into the new protocols due to the pandemic, and especially now with it being flu season, our team is continually having to adapt to new and changing procedures, helping to educate the public about these changes, and still provide patientcentered care. This deserves recognition, and we make a point to let our team know we see their efforts and appreciate what they do every day. I could not do my job without the whole team, and I let them know that.” —Neemet McDowell, Duncan, BC

regularly rather than big things infrequently.” —Kristy Pelke, Tavistock, ON

birthdays with order-in lunches of pizza and chicken or Chinese food.” —Cathy Savage, Winkler, MB “Pizza lunches.” —Marlene Shehata, Ottawa, ON

“We got a BINGO card and a word is announced every day until someone gets it. The winner gets a gift card. It is fun!!!” —Azmina Premji, Ottawa, ON


Check out the online version of this article at CanadianHealthcareNetwork.ca (click on the logo to see issues)

“Pot luck lunches through the year, with barbecues in summer. We also celebrate THIS MONTH’S QUESTION:

2020 has been a year like no other. As we head into a new year, what’s your best tip for a quick mental break when things are stressful?

“We start off every morning with a morning huddle. It’s a time where we can discuss things that are happening that day, but it’s also a time to socialize. One staff member tells jokes so we all start the day off with a laugh. We also take turns bringing in treats or doing a coffee or tea run. We try to do little things

Send your answers by November 23 to vwood@ensembleiq.com or simply respond in the comments section of the online version of this article on Canadianhealthcarenetwork.ca. (Be sure to include your full name)

One entrant will be randomly chosen to win a $50 Amazon gift card. The winner of September’s contest was Jenil Varia.

Do you have a problem you’d like to pose to your peers across Canada? Send your questions to vwood@ensembleiq.com

[Vol.7 No.9] NOVEMBER 2020



Vascepa : Power to reduce the risk of cardiovascular events1 the risk ®

Vascepa® demonstrated reductions in the risk of CV events vs. placebo (both in combination with statins)1* 2° endpoints

CV death†‡



(event n=174 vs. 213)

95% CI (0.66, 0.98)

Non-fatal myocardial infarction† Non-fatal stroke†

30 29


(event n=237 vs. 332)

95% CI (0.59, 0.82)


(event n=85 vs. 118)

95% CI (0.54, 0.94)

Vascepa® demonstrated a significant 25% reduction (event n=705 vs. 901) in time to first occurrence of cardiovascular death, MI, stroke, coronary revascularization or hospitalization for unstable angina (5-point MACE) vs. placebo (1° endpoint).1* 95% CI (0.68, 0.83) There was no statistically significant difference in risk between the Vascepa® and placebo groups for all-cause mortality.

A placebo-controlled trial with a 4.9-year median follow-up of statin-treated adult patients with elevated triglycerides and a high risk of cardiovasular events due to established cardiovascular disease or diabetes with at least 1 other CV risk factor.1*

Consider Vascepa®: The first and ONLY icosapent ethyl (IPE) prescription medication1§

To learn more, visit


Vascepa® (icosapent ethyl) is indicated to reduce the risk of cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization or hospitalization for unstable angina) in statin-treated patients with elevated triglycerides, who are at high risk of cardiovascular events due to: established cardiovascular disease, or diabetes, and at least one other cardiovascular risk factor Clinical use: Not indicated for pediatric use. Use in geriatrics is not associated with differences in safety or effectiveness, but greater sensitivity of some older individuals cannot be ruled out. Relevant warnings and precautions: • Not recommended in combination with or substituted for other products that contain omega-3 fatty acids • Increased incidence of bleeding • Caution in patients with known hypersensitivity to fish and/or shellfish • Periodic monitoring of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in patients with hepatic impairment is recommended during therapy with Vascepa® • Fertility • Not recommended in pregnancy and nursing For more information: Please consult the Vascepa® Product Monograph at https://health-products.canada.ca/dpd-bdpp/index-eng.jsp for important information relating to adverse reactions, drug interactions, and dosing/

administration information which have not been discussed in this piece. The Product Monograph is also available by calling HLS Therapeutics Inc. at 1-833-266-3423. * 8,179 statin-treated adult patients with elevated serum triglyceride levels (≥1.5 mmol/L to <5.6 mmol/L) who were also at high risk for atherothrombotic events. Patients either had established CVD or were at high risk for CVD and were randomized to either Vascepa® or placebo. Patients with established cardiovascular disease were at least 45 years of age and had a documented history of coronary artery disease, cerebrovascular or carotid disease, or peripheral artery disease. Patients with other risk factors for cardiovascular disease were at least 50 years of age and had diabetes and at least one additional major cardiovascular risk factor. 5-point MACE was defined as time to first occurrence of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Most patients at baseline were taking at least one other cardiovascular medication including anti-hypertensives (95%), anti-platelet agents (79.4%), beta blockers (70.7%), angiotensin-converting enzyme (ACE) inhibitors (51.9%), and angiotensin receptor blockers (ARB) (27.0%), with 77.5% taking either an ACE inhibitor or ARB. At baseline, while on stable background lipid-lowering therapy, the median LDL-C was 1.9 mmol/L. † Incidence rates of CV events per 100 patient years (Vascepa® vs. placebo): cardiovascular death, 1.0 vs. 1.2; non-fatal myocardial infarction, 1.4 vs. 2.0; non-fatal stroke, 0.5 vs. 0.7. ‡ CV death includes adjudicated cardiovascular deaths and deaths of undetermined causality. § Comparative clinical significance has not been established. CI, confidence interval; CV, cardiovascular; CVD, cardiovascular disease; LDL-C, low-density lipoprotein cholesterol; MACE, major adverse cardiovascular event. Reference: 1. HLS Therapeutics Inc. Vascepa® Product Monograph. 2019.

NEW Vascepa® is a registered trademark of the Amarin group of companies. © Copyright 2020 HLS Therapeutics Inc. HLS Therapeutics Inc., Etobicoke, Ontario M9W 6L2 VAS 20200413 E COM

(icosapent ethyl)

Drug News

A review of new launches, new indications, new dosage forms and Health Canada advisories


Emerade autoinjector: for treatment of anaphylaxis epinephrine 0.15 mg (approved, but not being marketed initially), 0.3 mg and 0.5 mg solution for injection in prefilled pen (autoinjector), Bausch Health.

INDICATIONS Emergency treatment of

anaphylactic reactions in patients who are at increased risk for anaphylaxis, including individuals with a history of anaphylactic reactions. ACTION Alpha adrenergic receptor stimulation by epinephrine counters the vasodilation and high vascular permeability that occurs during an anaphylactic reaction and which can lead to loss of intravascular fluid volume and hypotension. Beta-adrenergic receptor stimulation by epinephrine causes bronchial smooth muscle relaxation, which helps to alleviate bronchospasm, wheezing and dyspnea that may occur during anaphylaxis. Epinephrine also helps to relieve pruritus, urticaria and angioedema, and may be effective in relieving gastrointestinal and genitourinary symptoms of anaphylaxis because of its relaxant effects on the smooth muscle of the stomach, intestine and urinary bladder. DOSAGE The effective dose usually ranges from 0.005–0.01 mg/kg bodyweight. Children 15–30 kg: usual dose is 0.15 mg. Children > 30 kg: usual dose is 0.3 mg. Adolescents > 30 kg: follow adult dosage recommendations. Adults < 60 kg: recommended dose is 0.3 mg. Adults > 60 kg: recommended dose is 0.3–0.5 mg depending on clinical judgement. Administer an initial dose as soon as symptoms of anaphylaxis are recognized. If there is no clinical improvement or if deterioration occurs,



a second dose may be administered 5–15 minutes after the first injection. Ensure all individuals receiving emergency epinephrine are immediately transported to hospital (ideally by ambulance) for evaluation and observation even if symptoms appear to be improving. Patients/caregivers should be informed about the possibility of biphasic anaphylaxis which is characterized by initial resolution of symptoms followed by symptom recurrence a few hours later. ADMINISTRATION Give intramuscularly (can be self-administered) into the anterolateral aspect of the thigh, through clothing if necessary. Do not inject into the buttock. Press autoinjector gently against the outer side of the thigh; this will trigger the injection. A click can be heard when the injection goes into the muscle. Hold the autoinjector against the thigh for about five seconds. Lightly massage the injection site afterwards. ADVERSE EFFECTS MOST COMMON: Moderate anxiety, feelings of overstimulation, apprehensiveness, restlessness, tremor, weakness, shakiness, dizziness, sweating, tachycardia, palpitations, pallor, nausea and vomiting, headache, respiratory difficulties; symptoms usually subside quickly, especially with rest. MOST SERIOUS: Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia, have been reported at the injection site. Cases of gas gangrene have occurred when epinephrine is injected into the buttock. COMMENTS The first epinephrine autoinjector to be available in a 0.5 mg strength.


amifampridine 10 mg tablets (as amifampridine phosphate), Catalyst Pharmaceuticals (US). Canadian distributor Kye Pharmaceuticals, Mississauga, ON (1-888-822-7126).

INDICATIONS A potassium channel

blocker for the symptomatic treatment of Lambert-Eaton myasthenic syndrome in adults. DOSAGE Individually titrated. Recommended starting dose is 15 mg daily, taken orally in divided doses (usually 3 times daily). Extensively metabolized/acetylated by N-acetyltrans­ ferase 2 (NAT2). If the patient is known to be a NAT2 fast acetylator, the starting dose can be 30 mg daily. Increase the dose by 5 mg daily every three or four days while closely monitoring the patient for adverse reactions. Maximum single dose is 20 mg. Maximum recommended total daily dose is 80 mg. ADMINISTRATION Take orally in divided doses (3–4 times daily). May be taken without regard to food. COMMENTS Will be available only through specialty pharmacies. Patient support program can be contacted at 1-833-338-0524. Peyona caffeine citrate 20 mg/mL intravenous (IV)/ oral solution; 1 mL ampoules, Methapharm.

INDICATIONS Short-term treatment of

primary apnea of premature newborns. DOSAGE Recommended dosage regimen in previously untreated infants is a caffeine citrate loading dose of 20 mg/kg administered by slow IV infusion (over 30 minutes), using a syringe infusion pump or other metered infusion device. After 24 hours, maintenance doses of 5 mg/kg may be administered by slow IV infusion (over 10 minutes) every 24 hours. Alternatively, maintenance doses of 5 mg/kg may be administered by oral administration (e.g., through a nasogastric tube) every 24 hours. COMMENTS For use in neonatal intensive care units only. Plasma concentrations of caffeine may need to be monitored periodically throughout treatment in cases of incomplete clinical response, signs of toxicity or when adjusting doses in higher risk situations.

[Vol.7 No.9] NOVEMBER 2020


(Drug News continued)

be given slowly (e.g., 10 mL over 30–60 seconds).



amifampridine 10 mg tablets, Medunik Canada. Canadian distributor, Innomar Strategies.

tucatinib 50 mg and 150 mg tablets, Seattle Genetics (US). Canadian distributor: McKesson Specialty Distribution.

INDICATIONS Potassium channel blocker

INDICATIONS Used in combination

for symptomatic treatment of LambertEaton myasthenic syndrome in patients six years of age and older. DOSAGE Should be individualized based on disease severity, patient response and patient population. Patients weighing < 45 kg; start with 5–10 mg daily, in divided doses (2–3 times per day). Increase daily in 2.5–5 mg increments, divided in up to five doses per day. Maximum single dose is 10 mg. Maximum maintenance dose is 40 mg/d. Patients weighing ≥ 45 kg: start with 10–20 mg daily, in divided doses (2–3 times per day). Increase daily in 5–10 mg increments, divided in up to five doses per day. Maximum single dose is 20 mg. Maximum recommended maintenance dose is 80 mg/d (some patients may benefit from 100 mg/d). Extensively metabolized/acetylated by NAT2; use the lowest recommended starting dose in patients who are known NAT2 slow acetylators. ADMINISTRATION Can be taken without regard to food intake, but administration with food could mitigate paresthesia and abdominal discomfort. When patients require a dose of < 5 mg, have difficulty swallowing tablets or require a feeding tube, a 1 mg/mL suspension can be prepared (see product monograph for details). COMMENTS Patient support program can be contacted at 1-855-756-7660. Tomvi etomidate 2 mg/mL solution for IV injection; 10 mL or 20 mL single-use vials, SteriMax.

INDICATIONS Used in healthcare settings

for induction of general anesthesia and for supplementation of subpotent anesthetic agents during anesthesia for short operative procedures (e.g., dilation and curettage, cervical conization) in adults. DOSAGE Dose and rate of administration is individualized and titrated to the desired effect. Consult product monograph for details. ADMINISTRATION IV injections should 10

with trastuzumab and capecitabine for treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases. Intended for patients who have received prior treatment with trastuzumab, pertuzumab and trastuzumab emtansine, separately or in combination. DOSAGE 300 mg (two 150 mg tablets) taken orally twice daily (in combination with trastuzumab and capecitabine) until disease progression or unacceptable toxicity occurs. ADMINISTRATION Take doses approximately 12 hours apart, at the same time every day, with or without a meal. Tablets should be swallowed whole; do not chew, crush or split before swallowing. May be taken at the same time as capecitabine.


etanercept injection, Merck.

NEW INDICATIONS Now approved for

four new indications: 1. Reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients aged four to 17 years who have had an inadequate response to one or more disease-modifying antirheumatic drugs. 2. Reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in adults with psoriatic arthritis; can be used in combination with methotrexate in adults who do not respond adequately to methotrexate alone. 3. Treatment of adults with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. 4. Treatment of children (4–17 years of age) with chronic severe plaque psoriasis who are candidates for systemic therapy or phototherapy. (Originally indicated only for use in the treatment of moderately to severely active rheumatoid arthritis in adults and for reducing the

NOVEMBER 2020 [Vol.7 No.9]

signs and symptoms of active ankylosing spondylitis.) DOSAGE Varies according to indication and age; consult product monograph for details. Brilinta ticagrelor tablets, AstraZeneca.

NEW INDICATION Co-administered

with low-dose acetylsalicylic acid (ASA, 75–150 mg), to reduce the risk of a first myocardial infarction or stroke in patients with coronary artery disease, type 2 diabetes and a history of percutaneous coronary intervention, and who are also at high risk of developing an atherothrombotic event. (Two other indications approved earlier by Health Canada: 1. Co-administered with low-dose ASA for the secondary prevention of atherothrombotic events in patients with acute coronary syndromes. 2. Co-administered with low-dose ASA for the secondary prevention of atherothrombotic events in patients with a history of myocardial infarction (which occurred at least one year ago) and a high risk of developing an atherothrombotic event.) DOSAGE Patients with coronary artery disease and type 2 diabetes with a history of percutaneous coronary intervention: 60 mg twice daily. No loading dose is required. Treatment should be continued for as long as the patient remains at high risk of an atherothrombotic event and low risk of bleeding, for a duration of up to three years. Gardasil 9 human papillomavirus 9-valent vaccine, recombinant, suspension for injection, Merck.


for the vaccine’s use in boys/men has been extended to 9–45 years (originally 9–26 years). The vaccine is indicated in boys and men nine through 45 years of age for the prevention of infection caused by human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52 and 58, and the following diseases associated with the HPV types included in the vaccine: anal cancer caused by HPV types 16, 18, 31, 33, 45, 52 and 58; genital warts (condyloma acuminata) caused by HPV types 6 and 11; and anal intraepithelial neoplasia grades 1, 2 and 3 caused by


The FIRST and ONLY influenza vaccine in Canada made using cell-based manufacturing FLUCELVAX® QUAD is a quadrivalent inactivated vaccine indicated for active immunization of adults and children aged 9 years or older for the prevention of influenza disease caused by influenza virus subtypes A and B contained in the vaccine. The National Advisory Committee on Immunization (NACI) provides additional guidance on the use of the influenza vaccine in Canada. Please refer to the published Statement on Seasonal Influenza Vaccine for the current season.‡ Please consult the Product Monograph at www.seqirus.ca/ flucelvaxmonograph for contraindications, adverse reactions, drug interactions, and dosing information that have not been discussed in this piece. The Product Monograph is also available by calling us at 1-855-358-8966. † Comparative clinical significance has not been established. ‡ FLUCELVAX® QUAD is not listed in the NACI guidelines.

Learn More

Flucelvax is a registered trademark of Seqirus UK limited or its affiliates. © Seqirus Canada Inc. 2020 CA/XQIV/1019/0005E

Seqirus Canada Inc. Kirkland, Québec www.seqirus.ca 1.844.392.8582 514.221.4877

(Drug News continued)

HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58. (The vaccine is also indicated for use in girls and women nine through 45 years of age for the prevention of infection caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 and diseases associated with these HPV types.) DOSAGE 0.5 mL doses given according to a three-dose schedule (0, 2 and 6 months). Alternatively, individuals nine through 14 years of age can receive a two-dose schedule, with the second dose administered between five and 13 months after the first dose. If the second dose is administered earlier than five months after the first dose, a third dose should always be administered. Administer intramuscularly in the deltoid region of the upper arm or in the higher anterolateral area of the thigh. Lokelma sodium zirconium cyclosilicate powder for oral suspension, AstraZeneca.


indication for use as a potassium binder in the treatment of hyperkalemia in adults has been expanded to include patients on chronic hemodialysis. DOSAGE For patients on dialysis, Lokelma should only be dosed on nondialysis days. Recommended starting dose is 5 g once daily on every non-dialysis day. To establish normokalemia (4–5 mmol/L), the dose may be titrated up or down once weekly based on the predialysis serum potassium value after the long inter-dialytic interval (LIDI). Dose can be adjusted weekly in increments of 5–15 g once daily on non-dialysis days, or down to zero (dose interruption) for a few days to reach normokalemia. To maintain normokalemia, monitor pre-dialysis postLIDI serum potassium regularly (e.g., every four or more weeks). Administer orally as a suspension in water. Can be taken with or without food. Lynparza olaparib tablets, AstraZeneca.

NEW INDICATION Monotherapy for

the treatment of adults with deleterious or suspected deleterious germline and/ or somatic BRCA or ATM mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed 12

following prior treatment with a new hormonal agent. (Also indicated for use in the treatment of breast cancer, ovarian cancer and adenocarcinoma of the pancreas.) DOSAGE Two 150 mg tablets twice daily (600 mg/d). Continue treatment until progression of the underlying disease or unacceptable toxicity occurs. Patients receiving olaparib for mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently, or should have had bilateral orchiectomy. Tremfya/Tremfya One-Press guselkumab solution for injection, Janssen.

NEW INDICATION Treatment of adults

with active psoriatic arthritis, used alone or in combination with a conventional disease-modifying antirheumatic drug (e.g., methotrexate). (Originally indicated only for use in the treatment of adults with moderate-to-severe plaque psoriasis.) DOSAGE 100 mg given by subcutaneous (SC) injection at Week 0 and Week 4, followed by 100 mg SC maintenance dosing every eight weeks.


Esbriet: risk of liver injury Drug-induced liver injury (DILI), with transient and clinically silent elevations in transaminases, has been commonly reported in patients treated with Esbriet (pirfenidone). In rare cases, DILI has been associated with some fatal outcomes. Healthcare professionals are advised to: perform liver function tests (ALT, AST, bilirubin) before starting pirfenidone treatment, at monthly intervals during the first six months, and every three months thereafter; promptly measure liver function tests in patients who report symptoms that may indicate liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice); consider discontinuation or dose adjustments if liver enzyme elevations occur; avoid use in patients with severe hepatic impairment or endstage liver disease; use pirfenidone with caution in patients with pre-existing mild to moderate hepatic impairment. Fibristal: withdrawn due to risk of liver injury In late September 2020, Allergan voluntarily withdrew the uterine fibroid

NOVEMBER 2020 [Vol.7 No.9]

dug Fibristal (ulipristal acetate) from the Canadian market due to rare cases of severe liver injury requiring liver transplantation. A drug recall was also initiated at the retail pharmacy level. Imbruvica: no link with HLH A Health Canada safety review was unable to establish a link between the use of Imbruvica (ibrutinib) and the development of hemophagocytic lymphohistiocytosis (HLH). HLH is a rare life-threatening condition where a large number of immune cells attack and destroy other blood cells. The review was prompted by five international published cases and one Canadian case report. Health Canada will continue to monitor Imbruvica safety. Further details about these advisories and safety reviews can be obtained from the MedEffect Canada website: https://www.canada.ca/en/health-canada/services/ drugs-health-products/medeffect-canada.html and https://www.canada.ca/en/health-canada/services/ drugs-health-products/medeffect-canada/safetyreviews.html. Lu-Ann Murdoch, RPh, BScPhm, ACPR, is a consulting clinical editor for Pharmacy Practice +Business and drug information consultant for Pharmacist’s Letter.

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Practice Experts

Our pharmacist experts share information and ideas to support your daily practice


those with uncontrolled chronic pain.(5) Patient self-report of cannabis use is considered reliable, provided that fear of repercussions is minimized.(4) An effective initial screening question is simply “Have you smoked marijuana or used cannabis in any form in the last six months?”(4) For patients answering “yes,” more in-depth assessment using a validated screening tool, such as the Cannabis Use Disorder Identification Test–Revised (CUDIT-R) (https://bpac.org.nz/BPJ/2010/June/ docs/addiction_CUDIT-R.pdf), may be warranted. Table 1 lists diagnostic criteria for CUD.(3)


CANNABIS USE DISORDER – A GROWING ISSUE Cannabis use is on the rise in Canada. A 2019 survey found 16.8% of Canadians aged 15 or older used cannabis in the past three months and 6% reported daily or near daily use.(1) While many individuals use cannabis only recreationally, approximately 9% of frequent cannabis users will develop cannabis use disorder (CUD).(2) CUD is characterized by clinically significant functional impairment resulting from persistent and prolonged use.(3) Individuals with CUD often display a decline in school or work performance, relationship difficulties and social withdrawal.(3) Risk factors for development of CUD include younger age of first use, rapid progression to frequent use, concurrent use of other psychoactive substances, comorbid psychiatric disorders, stressful life events, peer use of drugs and social isolation.(3) 14

While many individuals use cannabis only recreationally, approximately 9% of frequent cannabis users will develop cannabis use disorder (CUD).

Assessing patients for problematic cannabis use While it is reasonable to screen all individuals for cannabis use, specific attention should be paid to high-risk populations, including adolescents, patients with comorbid psychiatric disorders, patients with other substance misuse (e.g., alcohol, tobacco) and

NOVEMBER 2020 [Vol.7 No.9]

For patients identified as having CUD, brief intervention and referral to treatment is recommended.(4) While the ultimate goal is sustained abstinence from cannabis, a harm reduction approach with realistic goal setting should be taken.(4) First-line treatments are cognitive behavioural therapy and/or motivational enhancement therapy, which are successful in promoting abstinence in up to 50% of patients.(3,4) If lack of availability or financial barriers preclude access to first-line therapies, general addiction counselling or peer support groups (e.g., Marijuana Anonymous) can be recommended.(5) Currently, no medications are indicated for treatment of CUD. A recent systematic review included 26 randomized controlled trials (RCTs) of adolescents or adults with CUD or heavy cannabis use.(6) Included studies evaluated the impact of medication on one or more of the following: abstinence, cannabis use, treatment retention and withdrawal symptoms.(6) Studies also included a wide variety of nonpharmacologic cointerventions.(6) Overall, no benefit was seen on any of the outcomes studied for the following drugs compared to placebo: bupropion, nefazodone (no longer marketed in Canada), vilazodone, escitalopram, fluoxetine, venlafaxine, buspirone, atomoxetine, clozapine, ziprasidone, topiramate or galantamine.(6)

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Approach to treatment, role of pharmacotherapy

Evidence was insufficient to determine the impact of lithium, divalproex, oxytocin and progesterone.(6) Medications showing benefit over placebo in at least one outcome of interest were gabapentin, N-acetylcysteine, dronabinol, and an experimental fatty acid amide hydrolase inhibitor.(6) A 12-week RCT of 50 adults found that gabapentin 1200 mg/day significantly reduced cannabis consumption compared to placebo.(7) Gabapentin was also associated with improvement in clinical depression and neurocognitive scores, improved treatment retention and less severe withdrawal symptoms.(7) An eight-week RCT of 116 youth aged 13–21 found that oral N-acetylcysteine 1200 mg/day significantly reduced cannabis consumption compared to placebo, based on negative urine testing (odds ratio: 2.35 (CI, 1.05–5.24); p=0.029).(8) No difference was noted in end-oftreatment abstinence rates.(8) A 12-week RCT in 302 adults found no benefit for N-acetylcysteine compared to placebo.(9) A 12-week RCT of 48 adults found dronabinol (a synthetic cannabinoid, no longer marketed in Canada) provided benefit for cannabis withdrawal symptoms, but abstinence rates were unchanged compared to placebo.(10) Other synthetic cannabinoids, such as nabilone, did not show clear benefit in any of the included studies.(6) Finally, in a four-week RCT of 70 males, those randomized to a fatty acid amide hydrolase inhibitor (thought to increase endocannabinoid activity) had fewer withdrawal symptoms and reduced cannabis use compared to placebo (mean 0.4 vs. 1.27 joints/day, p=0.0003).(11) Despite these positive findings, all studies were significantly limited by small sample sizes, heterogenicity of co-interventions, high drop-out rates, and other methodological flaws. More research is required before pharmacologic therapies can be routinely recommended for CUD.(6)

Pharmacist’s role

As a first point of contact with the healthcare system, pharmacists are ideally positioned to screen patients for problematic cannabis use. Particular attention should be paid to asking youth and other high-risk populations about cannabis use.(4) Similar to a smoking cessation approach, if problematic use


Diagnostic Criteria for Cannabis Use Disorder(3)

Criteria* A problematic pattern of cannabis use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period: • Cannabis often taken in larger amounts or over a longer period than was intended. • A persistent desire or unsuccessful efforts to cut down or control cannabis use. • A great deal of time spent in activities necessary to obtain cannabis, use cannabis, or recover from its effects. • Craving, or a strong desire or urge to use cannabis. • Recurrent cannabis use resulting in a failure to fulfill major role obligations at work, school or home. • Continued cannabis use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis. • Important social, occupational or recreational activities are given up or reduced because of cannabis use. • Recurrent cannabis use in situations in which it is physically hazardous. • Cannabis use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cannabis. • Tolerance, as defined by either of the following: a) A need for markedly increased amounts of cannabis to achieve intoxication or desired effect. b) Markedly diminished effect with continued use of the same amount of cannabis. • Withdrawal, as manifested by either of the following: a) The characteristic withdrawal syndrome for cannabis. b) Cannabis (or a closely related substance) is taken to relieve or avoid withdrawal symptoms. *Severity determined by number of criteria present: Mild: 2–3, Moderate: 4–5, Severe: 6+

is suspected, pharmacists can provide a brief educational intervention and encourage patients to set goals for reducing or stopping use. It is important to educate patients to expect physiological withdrawal symptoms within 24–72 hours of stopping heavy cannabis use. These may consist of irritability, anger, anxiety, depressed mood, insomnia and decreased appetite, and persist for one to two weeks.(3,5) Withdrawal symptoms may be mitigated by gradual reduction of cannabis intake and encouraging patients to adopt a healthy routine including adequate hydration, exercise and limiting caffeine, as well as connecting with a support person or group during the withdrawal period. Patient educational tools and other harm reduction resources are available from the Canadian Public Health Association (https://www.cpha.ca/ harm-reduction-health-promotion-andcannabis-screening-tools). Jillian Reardon, ACPR, PharmD, RPh, is a clinical pharmacist and lecturer at the Pharmacists Clinic, Faculty of Pharmaceutical Sciences, University of British Columbia. REFERENCES

1. Rotermann M. What has changed since cannabis was legalized? Statistics Canada, Catalogue no. 82003-X. Health Reports 2020;31(2):11-20. 2. Budney AJ, Roffman R, Stephens RS, et al. Marijuana dependence and its treatment. Addict Sci Clin Pract 2007;4(1):4-16.

3. American Psychiatric Association: Diagnostic and statistical manual of mental disorders, 5th ed. Arlington, VA: American Psychiatric Association; 2013. 4. Hjorthøj CR, Hjorthøj AR, Nordentoft M. Validity of timeline follow-back for self-reported use of cannabis and other illicit substances--systematic review and meta-analysis. Addict Behav 2012;37:225-33. doi:10.1016/j.addbeh.2011.11.025. 5. Turner SD, Spithoff S, Kahan M. Approach to cannabis use disorder in primary care: focus on youth and other high-risk users. Can Fam Physician 2014;60:801-8. 6. Kondo KK, Morasco BJ, Nugent SM, et al. Pharmacotherapy for the treatment of cannabis use disorder: a systematic review. Ann Intern Med 2020;172:398-412. doi:10.7326/M19-1105. 7. Mason BJ, Crean R, Goodell V, et al. A proof-ofconcept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults. Neuropsychopharmacology 2012;37:1689-98. doi:10.1038/npp.2012.14. 8. Gray KM, Carpenter MJ, Baker NL, et al. A double-blind randomized controlled trial of N-acetylcysteine in cannabis-dependent adolescents. Am J Psychiatry 2012;169:805-12. doi: 10.1176/appi. ajp.2012.12010055. 9. Gray KM, Sonne SC, McClure EA, et al. A randomized placebo controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend 2017;177:249-57. doi:10.1016/j. drugalcdep.2017.04.020. 10. Levin FR, Mariani JJ, Brooks DJ, et al. Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend 2011;116:142-50. doi:10.1016/j. drugalcdep.2010.12.010. 11. D’Souza DC, Cortes-Briones J, Creatura G, et al. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single site randomised controlled trial. Lancet Psychiatry 2019;6:35-45. doi:10.1016/S2215-0366(18)30427-9.

[Vol.7 No.9] NOVEMBER 2020


Practice Experts


ACEIs, ARBs AND COVID-19 Concerns have been raised regarding whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensinreceptor blockers (ARBs) may increase the susceptibility of patients to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. The putative mechanism for this increased risk suggests that ACEIs and ARBs may cause upregulation of angiotensin-converting enzyme 2 (ACE2), which is presumed to act as a viral receptor for SARS-CoV-2 to gain entry to host cells. However, retrospective cohort studies have not found any association with ACEI/ARB use and likelihood of receiving a positive SARS-CoV-2 test result. In addition, observational studies examining the effect of ACEI/ARB drugs on the risk of COVID-19 outcomes have not shown that these drug classes are associated with more severe COVID-19 disease. A more recent retrospective cohort trial examined whether use of ACEIs/ARBs versus other antihypertensive drugs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. A total of 4,480 confirmed COVID-19 patients from Denmark were included in the analysis. The sample included 895 patients who had used ACEIs/ARBs within the past six months and 3,585 nonusers. In the ACEI/ARB group, 18.1% patients died within 30 days versus 7.3% in the nonuser group. However, this was not shown to be significant after adjustments for age, sex and medical history (adjusted hazard ratio 0.83, 95% confidence interval [CI] 0.67â&#x20AC;&#x201C;1.03). In the analysis for COVID-19 susceptibility among patients with hypertension, ACEI/ARB use did not increase the risk of COVID-19 diagnosis compared with other antihypertensive 16


Our pharmacist experts share information and ideas to support your daily practice

ACEI/ARB use did not increase the risk of COVID-19 diagnosis compared with other antihypertensive drugs. drugs (adjusted hazard ratio 1.05, 95% CI 0.80â&#x20AC;&#x201C;1.36).

Implications for pharmacists

This study provides additional evidence


for the continued use of ACEI/ARB therapy in patients who are currently on these medications. It also supports starting these drugs in patients who have a specific indication for their use (e.g., left ventricular dysfunction, chronic kidney disease, secondary stroke prevention). REFERENCES

Fosbol EL, Butt JH, Ostergaard L, et al. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA 2020;324:168-77. Mackey K, King VJ, Gurley S, et al. Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV2infection in adults: a living systematic review. Ann Intern Med 2020;173:195-203. Solaru KW, Wright JT. COVID-19 and use of drugs targeting the renin-angiotensin-system. Am Coll Cardiology 2020; July 15. https://www.acc.org/latestin-cardiology/articles/2020/07/15/13/12/covid-19-anduse-of-drugs-targeting-the-renin-angiotensin-system (accessed August 6, 2020).


SGLT2 INHIBITORS AND RISK OF DIABETES KETOACIDOSIS Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, are used in the management of patients with type 2 diabetes. In patients with type 2 diabetes at high cardiovascular risk, they have also been shown to reduce the risk for myocardial infarction, heart failure, renal failure and cardiovascular mortality. Although these agents are generally well tolerated, a possible increased risk for diabetes ketoacidosis (DKA) has been noted based on spontaneous adverse drug reaction reports. A large, population-based cohort study assessed the risk for DKA in patients prescribed SGLT2 inhibitors compared with dipeptidyl peptidase-4

NOVEMBER 2020 [Vol.7 No.9]

Most patients who develop DKA while on a SGLT2 inhibitor will have a precipitating event, such as dehydration, infection, surgery or change in insulin dose. (DPP-4) inhibitors. Using data from seven Canadian provinces and the United Kingdom, 208,757 new users of SGLT2 inhibitors were matched 1:1 to new DPP-4 users. Canagliflozin was used by

Implications for pharmacists

Most patients who develop DKA while on a SGLT2 inhibitor will have a precipitating event, such as dehydration, infection, surgery or change in insulin dose. The US Food and Drug Administration has recently recommended safety labelling changes for SGLT2 inhibitors: canagliflozin, dapagliflozin and empagliflozin should be discontinued three days before scheduled surgery, and ertugliflozin should be stopped at least four days before. Once the patient’s oral intake is back to baseline, the SGLT2 inhibitor may be restarted. REFERENCES

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Douros A, Lix LM, Fralick M, et al. Sodium-glucose cotransporter-2 inhibitors and the risk for diabetic ketoacidosis: a multicenter cohort study. Ann Intern Med 2020 (published online ahead of print). doi:10.7326/M20-0289.

42.3% of patients, dapagliflozin by 3.7% and empagliflozin by 27.0%. Overall, 521 patients were diagnosed with DKA, for an overall incidence rate of 1.41 per 1,000 person years. For SGLT2 inhibitors, the rate was 2.03 per 1,000 person years,

which was about three times that seen with patients receiving DPP-4 inhibitors (0.75 per 1,000 person years). The rate for individual agents was 1.86 per 1,000 person years for dapagliflozin, 2.52 for empagliflozin and 3.58 for canagliflozin.



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FDA: Suspend SGLT2 inhibitors before surgery. March 17, 2020. https://www.healio.com/news/ endocrinology/20200317/fda-suspend-sglt2-inhibitorsbefore-surgery (accessed August 13, 2020).

Sandra Knowles, BScPhm, is a drug information pharmacist with Sunnybrook Health Sciences Centre in Toronto.

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Helping Patients Achieve Glycemic Control Through Informed Technology and Behaviour Change Strategies


By John Papastergiou, BSc, BSc Phm, and Tom Smiley, BSc Phm, Pharm D, CTE


Upon completion of this learning activity, pharmacists will be better able to: 1. Discuss the current prevalence, costs and risks associated with diabetes in Canada 2. Describe how the evolution of technologies and patient needs have enhanced the pharmacist’s role in providing diabetes care 3. Implement strategies to overcome barriers that prevent patients with diabetes from engaging in care activities 4. Review how blood glucose meter features can help patients improve self-monitoring of their blood glucose (SMBG) 5. Initiate and participate in effective interactions with patients, utilizing principles of behaviour change management


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Symbicort® Turbuhaler®


SYMBICORT¨ What is Symbicort® Turbuhaler® indicated for? Pr Symbicort® Turbuhaler® (budesonide and formoterol fumarate dihydrate) is indicated for the treatment of asthma in patients 12 years and older with reversible obstructive airways disease.1

Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever Therapy can be used for the treatment of mild persistent asthma in patients 12 years and older. Symbicort® Turbuhaler® can be used according to three different treatment approaches: A. Symbicort® Turbuhaler® Anti-Inflammatory Reliever Therapy: in patients with mild persistent asthma, Symbicort® 200 Turbuhaler® is taken as needed for relief of asthma symptoms when they occur. Symbicort® Turbuhaler® has not been evaluated in patients whose asthma can be managed by occasional use of a rapid onset, short duration, inhaled beta2-agonist. B. Symbicort® Turbuhaler® Anti-Inflammatory Reliever plus Maintenance Therapy: in patients with moderate or severe asthma, Symbicort® 100 Turbuhaler® or Symbicort® 200 Turbuhaler® are taken both as daily maintenance therapy and as needed for relief of asthma symptoms when they occur. C. Symbicort® Turbuhaler® Maintenance Therapy: in patients with moderate or severe asthma, Symbicort® Turbuhaler® is taken as a fixed-dose daily treatment with a separate short-acting bronchodilator for relief of symptoms when they occur. Once asthma control is achieved and maintained, the patient should be assessed at regular intervals.

What were the results for Symbicort® in some of the key clinical trials? The efficacy of Symbicort® was evalutated in a clinical trial program of the trials below.

SYGMA 1 study – mild persistent asthma patients Symbicort ® 200 Turbuhaler® Anti-Inflammatory Reliever therapy:1,3¶§ vs. terbutaline (terb 0.5 mg prn) demonstrated mean % WCAW 34.4 vs. 31.1% (primary endpoint, p=0.046; [odds ratio, 1.14; 95% CI, 1.00 to 1.30]).¥

vs. budesonide maintenance therapy (bud 200 µg bid + terb 0.5 mg prn), secondary analysis of the primary endpoint (in terms of WCAW) showed that non-inferiority for asthma symptom control was not met for Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever therapy vs. budesonide maintenance therapy (bud 200 µg bid + terb 0.5 mg prn) (lower limit of the 2-sided 95% CI ≥ 0.8 for non-inferiority [OR] 0.64, p=NA). vs. terbutaline (terb 0.5 mg prn) demonstrated 64% (0.07 vs. 0.20) lower annualized rate of severe exacerbations (secondary endpoint, p<0.001; annualized exacerbation rate: 0.07 [95% CI 0.06, 0.09] vs. 0.20 [95% CI 0.16, 0.24], respectively; [RR] 0.36, 95% CI 0.27, 0.49). Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever therapy vs. budesonide maintenance therapy + terbutaline reliever therapy (bud 200 µg bid + terb 0.5 mg prn):1,3¶§ Comparable reduction in severe exacerbation rate (0.07 vs. 0.09) with an 83% reduction in median ICS load (48.3 vs. 276.2 mcg/day) demonstrated (secondary endpoint, p=0.28; annualized severe exacerbation rate: 0.07 [95% CI 0.06, 0.09] vs. 0.09 [95% CI 0.07, 0.11], [RR] 0.83, 95% CI 0.59, 1.16).

SYGMA 2 study – mild persistent asthma patients Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever therapy vs. budesonide maintenance therapy (bud 200 µg bid + terb 0.5 mg prn):1,5£#§ Comparable reduction (0.11 vs. 0.12) in severe exacerbation rate with a 75% reduction in median ICS load (52.9 and 214.1 mcg/day) demonstrated (primary endpoint, p=na; annualized severe exacerbation rate: 0.11 [95% CI 0.10, 0.13] vs. 0.12 [95% CI 0.10, 0.14]; [RR] 0.97, 95% CI 0.78, 1.20).

COMPASS study – moderate to severe asthma patients Symbicort ® 200 Turbuhaler® Anti-Inflammatory Reliever) plus Maintenance therapy (Symbicort® 200 Turbuhaler® 1 inhl bid + Symbicort® 200 Turbuhaler® prn) vs. fluticasone/salmeterol maintenance + terbutaline (flut/salm 125/25 µg 2 inhl bid + terb 0.4 mg prn) demonstrated:6¢ 39% (125 vs. 208; number of severe exacerbations) reduction in severe exacerbations (secondary endpoint, p<0.001).6 ¶ Randomized, double-blind, parallel-group, 52-week study compared Symbicort®200 Turbuhaler® AntiInflammatory Reliever therapy to terbutaline (0.5 mg prn) or budesonide maintenance therapy (bud 200 µg bid + terb 0.5 mg) in patients with mild persistent asthma (N=3836 patients).1,3 § Severe exacerbation was defined as worsening asthma leading to the use of systemic glucocorticoids for ≥3 days, inpatient hospitalization, or an emergency department visit leading to the use of systemic glucocorticoids.3 ¥ WCAW was a composite endpoint capturing asthma symptoms, night-time awakenings, lung function, use of as-needed medication, and prescription of ICS and/or systemic glucocosteroid treatment for asthma. WCAW had 3 possible values: well-controlled, not-well-controlled and missing. £ Randomized, double-blind, parallel-group, 52-week study compared Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever therapy (placebo bid + Symbicort® 200 Turbuhaler® prn) to budesonide maintenance therapy (bud 200 µg bid + terb 0.5 mg) in patients with mild persistent asthma (N=4176 patients).1,5 # For the comparison of Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever therapy vs. budesonide bid, an upper limit of the 2-sided 95% CI <1.20 indicates Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever therapy was noninferior to budesonide bid.1  Randomized, double-blind, double-dummy, parallel-group, 6-month study compared Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever plus Maintenance therapy (Symbicort® 200 Turbuhaler® 1 inhl bid + Symbicort® 200 Turbuhaler® prn) to fluticasone/ salmeterol maintenance + terbutaline (flut/salm 125/25 µg 2 inhl bid + terb 0.4 mg prn) or Symbicort® 400/12 µg bid Maintenance therapy + terbutaline (Symbicort® 400/12 µg 1 inhl bid + terb 0.4 mg prn) in patients with moderate to severe asthma (N=3335).1,6 ¢ Severe exacerbations were defined as deterioration in asthma resulting in hospitalization or emergency room treatment or the need for oral steroids for ≥3 days (as judged by the investigator).5,6

Symbicort® 200 Turbuhaler® Anti-Inflammatory Reliever plus Maintenance therapy (Symbicort® 200 Turbuhaler® 1 inhl bid + Symbicort® 200 Turbuhaler® prn) vs. Symbicort® 400/12 µg bid Maintenance therapy + terbutaline: (Symbicort® 400/12 µg 1 inhl bid + terb 0.4 mg prn) demonstrated: 28% (125 vs. 173; number of severe exacerbations) reduction in severe exacerbation (secondary endpoint, p=0.0048††) See Compass study parameters “” and “¢” on previous page. Symbicort Turbuhaler Maintenance Therapy • In a study of moderate-to-severe adult and adolescent asthmatics not well-controlled on inhaled glucocorticosteroids alone (≥ 750 mcg ICS daily), Symbicort® Turbuhaler® dosed twice daily (total daily dose 1600/48 mcg) was more effective than budesonide dosed twice daily (total daily dose 1600 mcg) in increasing morning PEF over 12 weeks of treatment (mean difference was 32.9 L/min, p<0.001). Statistically significant improvements were also seen for evening PEF (p<0.001), total asthma symptom score (p=0.005), daytime asthma symptoms (p<0.001), symptom free days (p<0.001), use of rescue medication (p<0.001), rescue free days (p<0.001), asthma control days (p<0.001), time to first mild exacerbation (p=0.003) and FEV1 (p<0.001).1

• Total maximum of 8 inhalations of Symbicort® per day. Not to exceed 6 inhalations on any single occasion. • A persistent increase in the use of Symbicort® 200 Turbuhaler® as needed indicates a deterioration of asthma control and the patient’s condition should be re-evaluated to determine the appropriate treatment. * Symbicort® 100 Turbuhaler® should not be used as Symbicort® Anti-Inflammatory Reliever Therapy.

When was the onset of effect seen with Symbicort® compared to salbutamol? Symbicort® demonstrated rapid onset of effect—as early as 3 minutes —post-administration, similar to salbutamol (FEV1; secondary endpoint)1,2**†

How is Symbicort® prescribed?1



Contraindications: • Hypersensitivity to inhaled lactose Most serious warnings and precautions: Risk of serious asthma-related events – hospitalizations, intubations and death: Use of long-acting beta2-agonists (LABA) as monotherapy (without inhaled corticosteroids [ICS]) may increase the risk of asthma-related death and the risk of asthma-related hospitalizations in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone Asthma reliever medication: Inform patients to have reliever medication available at all times. Asthma patients should be clearly instructed to use medication for relief of asthma symptoms (e.g., Symbicort® Turbuhaler®, or salbutamol). Excessive use and use with other LABA products: Do not exceed the recommended Symbicort® Turbuhaler® dose. Cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Use in adolescents: Periodic reassessment should be considered as severity of asthma may vary with age. Possible systemic effects, which may occur with any inhaled corticosteroid, include growth retardation in children and adolescents. Physicians should closely

Adapted from Balanag VM et al.2 IC: Confidence interval; RR: rate ratio; ICS: Inhaled corticosteroid; WCAW: 3 possible values: wellcontrolled, not well-controlled and missing; FEV: Forced expiratory volume. p-value based on Poisson regression. ** Comparative clinical significance has not been established. † Randomized, double-blind, double-dummy, parallel-group 3-hour study. Patients received 2 doses, 5 minutes apart of either Symbicort® 400/12 µg 2 inhalations (total dose=1600/48 µg; n=55) or salbutamol 100 µg 8 inhalations (total dose=1600 µg; n=48).2 2 ‡ Study drug was administered at -5 and 0 minutes.

follow the growth of adolescents taking long-term corticosteroids and weigh the benefits of asthma control against the possible risk of growth suppression. Systemic effects of corticosteroids: May occur with any inhaled corticosteroid and include Cushing’s syndrome, Cushingoid features and adrenal suppression, decrease in bone mineral density, cataract and glaucoma. Any inhaled corticosteroid should be titrated to the lowest dose at which effective control is maintained. Possible systemic effects, which may occur with any inhaled corticosteroid, include growth retardation in children and adolescents. Other relevant warnings and precautions: • Maintenance treatment with ICS should not be stopped abruptly, but tapered gradually under supervision • Cardiovascular effects • Candidiasis • Hyperglycemia, hypokalemia • Enhanced effect of corticosteroids on patients with hypothyroidism and cirrhosis • Adrenal insufficiency in patients transferred from systemic steroid • Decreased bone mineral density • In rare cases, systemic eosinophilic conditions • Susceptibility or decreased resistance to infection • Glaucoma, increased intraocular pressure and cataracts • Paradoxical bronchospasm • Potential risk during pregnancy, labour, delivery or nursing • Special caution in patients >65 years of age with concomitant cardiovascular disease • Control of asthma should be monitored

• HPA axis function and hematological status should be assessed periodically For more information: Consult the Product Monograph at azinfo.ca/symbicort/ pm796 for important information regarding adverse reactions, drug interactions and dosing. The Product Monograph is also available by calling AstraZeneca Canada at 1-800-668-6000. References 1. Symbicort® Turbuhaler® Product Monograph. Astrazeneca Canada Inc. September 26, 2019. 2. Balanag VM, Yunus F, Yang P-C et al. Efficacy and safety of budesonide/formoterol compared with salbutamol in the treatment of acute asthma. Pulm Pharmacol Ther 2006;19(2):139-47. 3. O’Byrne PM, FitzGerald JM, Bateman ED et al. Inhaled combined budesonide-formoterol as needed in mild asthma. (Symbicort Given as Needed in Mild Asthma [SYGMA] 1 trial). N Engl J Med 2018;378(20):1865-76. 4. O’Byrne PM, FitzGerald JM, Bateman ED et al. Risk of a severe exacerbation following higher reliever use: posthoc analysis of SYGMA 1 in mild asthma. Eur Respir J 2018;52 (suppl 62):OA1680. 5. Bateman ED, Reddel HK, O’Byrne PM et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. (Symbicort Given as Needed in Mild Asthma [SYGMA] 2 trial). N Engl J Med 2018;378(20):1877-87. 6. Kuna P, Peters MJ, Manjra AI et al. Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations. Int J Clin Pract 2007;61(5):725-36. SYMBICORT®, TURBUHALER® and the AstraZeneca logo are registered trademarks of AstraZeneca AB, used under license by AstraZeneca Canada Inc.

This Q&A is published by Ensemble IQ, 20 Eglinton Avenue West, Suite 1800, Toronto, ON M4R 1K8, Telephone: 416-256-9908. No part of this Q&A may be reproduced, in whole or in part, without the written permission of the publisher. © 2020



5 Tips




hether being used to treat asthma or chronic obstructive pulmonary disease (COPD), respiratory inhalers have very high nonadherence rates at 30%–70%.(1) As higher inhaler adherence is associated with positive health outcomes, improved disease control and a reduction in mortality,(2) how can we as pharmacists do better? What are the barriers to adherence, and how can we


Are patients on the right inhalers? Assess inhaler therapy in accordance with guideline recommendations, as summarized for asthma (Table 1, online) and COPD (see below). If symptoms are poorly controlled, determine if it is due to poor adherence versus inadequate therapy, prior to adding or adjusting medications.(4) COPD: The stepwise approach to COPD, like asthma, depends on the severity of the disease. As per the 2019 GOLD guidelines,(6) severity is predominantly based on the number of exacerbations and/or hospitalizations. It is categorized into Groups A to D, which range in severity from mild to severe. From an inhaler perspective, we start with a bronchodilator, switch classes if not adequate, then add either a long-acting betaagonist (LABA) or long-acting 20

muscarinic antagonist (LAMA). The next step is to combine a LABA and LAMA, then consider adding an inhaled corticosteroid (ICS) to the LABA. Oral therapy may be considered subsequently.(6) A major recent change in COPD treatment has been the addition of more choices in each inhaler class.


Know what’s what in inhaler products and devices on the market Adherence barriers often lie with the devices themselves: cost, technique and use. Manufacturers are now looking to enhance adherence by offering different inhaler formats, better drug deposition, as well as combination and longer-acting formulations. Inhalers can be easily categorized by drug class and indication (Table 2). Engage patients in the decision-making process about inhaler type, as some may NOVEMBER 2020 [Vol.7 No.9]

help patients use their inhaled medications more consistently? Nonadherence can be unintentional or intentional. We should be aware of intentional nonadherence, but it is often more challenging to modify, as change is rarely achieved through the usual approaches. This article provides five tips for improving unintentional nonadherence, as interventions such as simplifying treatment regimens and providing education can have a big impact.(3)

be better suited to them (see attributes in Table 3). Ensure drug coverage whenever possible; an expensive device that isn’t covered is much less likely to be used.


Manage expectations Patients need to understand the role of the prescribed medications and how to use them. As pharmacists, we need to know if there are any patient concerns that may preclude use. We have unique opportunities for teaching and interaction, and can assess if the devices are working and appropriate. Assess and identify patient preferences and barriers to treatment: • Do they think it will help, or are they worried about harm? Are there side effect concerns you can put in perspective? • Medication-taking experience: inhalers with low taste or smell may be more

palatable, but less confirmatory that a dose has been taken (e.g., salbutamol metered-dose inhaler vs. dry powder inhaler) • Trusting the inhaler as a medication: unlike oral medications, which have a strong visual confirmation, inhalers require a greater degree of trust in the healthcare provider. Reassure patients that they are taking an effective medication. • Are they angry or upset about their diagnosis? This can be a significant barrier to medication adherence. Active listening and periodic checkins may help.


Play the “matching game” Assist patients and physicians in deciding which inhalers are most appropriate for the indication and for the individual. • Ensure patients are on the right step in therapy, and help them select the most convenient inhaler and combination.

• Tailor therapy to patient/ caregiver factors: - Age at onset/current age: young child vs adolescent vs. older adult(2) - Cognitive and dexterity factors - Cultural norms - Who will administer the inhalers? Are they trained/ skilled? Any concerns that may prevent administration? • Use all resources available (demos, apps, YouTube teaching videos, manufacturer resources), to ensure the patient is familiar with how to use the inhaler. • Consider if matching inhalers or distinct ones are preferred. • Streamline or step-down therapy whenever possible.



Inhalers grouped by drug class and indication*

= Asthma & COPD

= Specific use in COPD (as indicated)





SABA 1) Salbutamol (Ventolin, Airomir) 2) Terbutaline (Bricanyl) SAMA 1) Ipratropium (Atrovent)

1) Beclomethasone (Qvar) 2) Budesonide (Pulmicort) 3) Ciclesonide (Alvesco) 4) Fluticasone furoate (Arnuity Ellipta) 5) Fluticasone propionate (Flovent) 6) Mometasone (Asmanex)

Must be combined with ICS for asthma 1) F  ormoterol (Foradil, Oxeze) 2) S  almeterol (Serevent)

COPD indication 1) Aclidinium/formoterol (Duaklir Genuair) 2) Glycopyrronium/indacaterol (Ultibro Breezhaler) 3) Tiotropium/olodaterol (Inspiolto Respimat) 4) Umeclidinium/vilanterol (Anoro Ellipta)





Ipratropium/ salbutamol (Combivent Respimat)

1) Budesonide/formoterol (Symbicort) 2) Fluticasone/salmeterol (Advair Diskus/MDI) 3) Fluticasone furoate/ vilanterol (Breo Ellipta) 4) Mometasone/ formoterol (Zenhale)

COPD indication 1) Tiotropium (Spiriva Handihaler or Respimat) 2) Aclidinium (Tudorza Genuair) 3) Umeclidinium (Incruse Ellipta) 4) Glycopyrronium (Seebri Breezhaler)

COPD indication 1) F  luticasone furoate/ vilanterol/ umeclidinium (Trelegy Ellipta)

Asthma indication 1) Mometasone/ indacaterol (Atectura Breezhaler)

Asthma indication 1) Tiotropium (Spiriva Respimat)

Asthma indication 1) Mometasone/indacaterol/ glycopyrronium (Enerzair Breezhaler)

Use technology and follow up Approaches to teaching and follow-up should be ageappropriate for the person using the inhaler. Parents of young children with asthma will have different needs from the teenager with asthma, as will the older adult with COPD. Identifying your patient and following through can yield significant benefits. In a community setting, make take-home or online resources available. Examples may include website links, YouTube videos, apps, electronic reminders or text messages. Some patients may benefit from additional counselling or support services. At each encounter, assess inhaler technique, provide encouragement and ensure the inhaler is meeting the patient’s needs and expectations; if not, adjust or educate. Pharmacy technicians can help by providing instructions on how to operate medical devices such as inhalers (where jurisdiction permits),(8) identifying patients who may benefit from further assessment by a pharmacist and directing patients to pharmacy resources. Add value with smoking cessation or seasonal allergy resources.

= Specific use in asthma (as indicated)

COPD indication Indacaterol (Onbrez)

COPD–chronic obstructive pulmonary disease; ICS–inhaled corticosteroid; LABA–long-acting beta-agonist; LAMA–long-acting muscarinic antagonist (also known as long-acting anticholinergic [LAAC]); SABA–short-acting beta-agonist; SAMA–short-acting muscarinic antagonist *Generics may be available for some of the listed products


Attributes of Canadian inhaler devices(7)



Breath control

Dose indicator

Dose counter


Multistep pill set-up

Low inspiratory effort required


No, but visible if no dose in device


Open cover

Forceful inhalation required

Yes, audible click when dose loaded

Indicator if almost empty


Open mouthpiece, press button

Some breath control required

Yes, audible click if dose taken correctly

Indicator/lock if empty


Priming required

Inspiratory control required


Indicator if almost empty

Metered-dose inhaler (MDI)

Shaking and priming required

Inspiratory control required (unless with spacer)


Most: No Zenhale: Yes


Twist dial on bottom

Forceful inhalation required

Yes, audible click when dose loaded

Yes, or indicator if almost empty


Open mouthpiece

Forceful inhalation required

Yes, audible click when dose loaded



Multistep pill set up

Inspiratory control required


No, but visible if no dose in device


don’t assure adherence, but assessment at each visit is helpful. The five tips presented in this article will help provide a framework for enhancing adherence to inhaler therapy.

As healthcare providers, it is often easy to focus on what is the “right medication” and the right way to take it. While this is an important first step in assessing medication therapy, medications only work if the patient takes them. Prescription filling patterns

Sara Ingram (sara.ingram@utoronto. ca) is an adjunct lecturer and APPE clinical coordinator at the Leslie Dan Faculty of Pharmacy, University of Toronto. As a clinical pharmacist

[Vol.7 No.9] NOVEMBER 2020

since 2005, she worked in Emergency Medicine for 12 years, and has coordinated the Asthma/COPD seminars at the Faculty of Pharmacy since 2011. References and Table 1 are available in the online version of this article. Click on the Pharmacy Practice+Business logo to find this issue.

www.CanadianHealthcareNetwork.ca/ pharmacists/




1st retinoid indicated in face and/or truncal acne1,2 ▲



Acne treatment for the face and trunk What is AKLIEF® indicated for? AKLIEF is indicated for the topical treatment of acne vulgaris of the face and/or trunk in patients 12 years of age and older.3 What is the incidence of truncal acne? In an evaluation of 696 patients, it was found that 52% of facial acne patients also had truncal acne. Of the patients that presented in this evaluation with a main complaint of only facial acne, 22.4% also had truncal involvement, which was only identified after a clinical examination of the chest and/or back. The patients that presented with truncal acne vulgaris were also surveyed in this evaluation, and about 3 out of 4 said they were interested in treatment for their truncal acne specifically, whether or not they mentioned truncal involvement as part of their main complaint.4* What is AKLIEF? • AKLIEF is the only prescription topical medication in Canada that is indicated in truncal acne as well as facial acne.1 • Trifarotene is a retinoid-like compound that consists of a terphenyl acid derivative that belongs to a new generation of the pharmacological class of retinoid acid receptor γ (RARγ) (gamma) agonist.3 What is the mechanism of action of AKLIEF?3†‡ • Biochemical and pharmacological profile studies have demonstrated that trifarotene is a potent modulator of cellular differentiation, keratinization and inflammatory processes all of which represent important features in the pathology of acne vulgaris. • Although the exact mode of action of trifarotene is unknown, in primary pharmacology studies, trifarotene has shown a high RAR activity and a very high selectivity for RAR γ (gamma) the receptor subtype present in keratinocytes and recognized to be the most relevant in acne over RARα and RARβ.

Pharmacodynamics AKLIEF produced the same comedolytic effect as other retinoids at a 10x lower dose in the Rhino-mouse model. In addition, trifarotene has also shown anti-inflammatory and depigmenting activities.3† Absorption and elimination Steady state conditions were achieved in both adults and pediatric subjects (12-18 years old) following 2 weeks of topical administration; and no drug accumulation is expected with long-term use. Overall, systemic exposure levels were low and similar between adult and pediatric (12-18 years old) populations. The terminal half-life ranged from 2 to 9 hours in patients receiving a once daily cutaneous application of AKLIEF.3 What was the efficacy of AKLIEF in clinical trials? AKLIEF demonstrated superior efficacy vs vehicle for facial and truncal acne.3§

TRUNK The onset of effect for PGA was at week 8 (secondary endpoint) for studies 18251 and 18252.3§ INFLAMMATORY LESIONS

On average, AKLIEF demonstrated 57.4% fewer inflammatory lesions from baseline to Week 12 (ITT, MI) vs 50% reduction with vehicle (p<0.001). Significant reduction in truncal inflammatory lesions at Week 12 vs vehicle INFLAMMATORY LESIONS Mean absolute change from baseline



LS mean (SE)

-21.4 (0.54)

-18.8 (0.55)

LS mean difference from vehicle (95% CI)

-2.5 (-4.0, -1.1)


FACE The onset of effect for IGA was at week 4 for study 18251.3§ INFLAMMATORY LESIONS


On average, AKLIEF demonstrated 54.4% fewer inflammatory lesions from baseline to Week 12 (ITT, MI) vs 44.8% reduction with vehicle (p<0.001). Significant reduction in facial inflammatory lesions at Week 12 vs vehicle INFLAMMATORY LESIONS Mean absolute change from baseline LS mean (SE) LS mean difference from vehicle (95% CI)



-19.0 (0.50)

-15.4 (0.51)

Patient ID: 18251-8511-004. Age: 16 years; gender: female. Individual results may vary. Trial results may not be representative of the general population.

Please see the Product Monograph for complete clinical trial results.

-3.6 (-4.9, -2.2)

Patient ID: 8665-006. Age: 15 years; gender: male. Individual results may vary. Trial results may not be representative of the general population.

RAR=retinoic acid receptor; LS=least square; SE=standard error; ITT=intent-to-treat; MI=multiple imputation; IGA=Investigator Global Assessment; PGA=Physician Global Assessment ▲ Comparative clinical significance is unknown. * US study across 5 cities. Patients were assessed to evauate the frequency and severity of truncal acne vulgaris. † Clinical significance is unknown. ‡ The exact mode of action for trifarotene is unknown. § Phase III, double-blind, randomized, vehicle-controlled, 12-week study of 1208 subjects (AKLIEF n=612; vehicle n=596) with moderate facial and truncal acne vulgaris. The primary endpoint was rate of success on the face, as determined by the Investigator’s Global Assessment (IGA) (clear or almost clear and ≥2 grade improvement), and absolute change in facial inflammatory and non-inflammatory counts from baseline to Week 12. The secondary endpoint was rate of success on the trunk, as determined by the Physician’s Global Assessment (PGA) (clear or almost clear and ≥2 grade improvement), and absolute change in truncal inflammatory and non-inflammatory counts from baseline to Week 12. The definitions of severity for the 5-point IGA (face) and PGA (trunk) scales were the same: 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate) and 4 (severe).4

How is AKLIEF administered?3 Apply a small amount of AKLIEF to provide a thin layer to the affected areas of the face and/or trunk once a day, in the evening, on clean and dry skin. • One pump actuation should be enough to cover the face (i.e., forehead, cheeks, nose, and chin). Apply a thin layer to cover the entire affected areas. • Two pump actuations should be enough to cover the upper trunk (i.e., reachable upper back, shoulders and chest). • One additional pump actuation may be used for middle and lower back if acne is present. • Hands should be washed after applying AKLIEF. The use of a moisturizer before and after is recommended as frequently as needed from the initiation of treatment, while allowing sufficient time before and after the application of AKLIEF to allow the skin to dry. • Using too much AKLIEF, or using it more than once a day, may increase the risk of skin irritation. • Avoid using AKLIEF on skin areas with cuts, abrasions, eczema or on sunburned skin.

include application site reactions, such as skin irritation characterized by local cutaneous reactions such as erythema, scaling, dryness, and stinging/burning.3 • Most of these treatment-related adverse reactions are mild to moderate, with few being severe.3 • Maximum severity typically occurred within the first 4 weeks of treatment, and decreased with continued use of the medication 3

COUNSELLING OPPORTUNITY In your patients diagnosed with facial acne, consider asking them if they have any truncal acne as well—their back, shoulders and/or chest. Recommend that your patients avoid skin products that may dry or irritate their skin such as harsh soaps, cleansers, astringents, cosmetics that have strong skin drying effects and products containing high levels of alcohol, spices or limes. Advise your patients to use a non-comedogenic moisturizer (e.g., Cetaphil Moisturizing Lotion or Cream) to help minimize irritation.

Discontinue treatment Discontinue treatment if a severe local inflammatory response is experienced. Reinstitute therapy when the reaction has subsided, initially applying the preparation less frequently (e.g. every other day). Once-daily application may be resumed if it is judged that the patient is able to tolerate the treatment. Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance.3 Are there local cutaneous reactions associated with AKLIEF? Certain side effects, such as erythema, dryness, scaling, burning or pruritus, are associated with the application of all retinoids, and can also be expected with AKLIEF. • Treatment-related adverse reactions typically associated with the use of AKLIEF Clinical use: Safety and effectiveness have not been established in children under 12 years or geriatric patients (≥65year). Contraindications: • Eczema or seborrheic dermatitis • Pregnancy or women planning a pregnancy Most serious warnings and precautions: For external use only, not for ophthalmic use. Pregnancy or planning a pregnancy: Rare reports of birth defects associated with topical retinoids during pregnancy. Women of child-bearing potential should be informed of potential risks and use effective birth control measures. Other relevant warnings and precautions: • Discontinue use if allergic/hypersensitivity reactions occur • Avoid contact with eyes, lips, angles of the nose, mucous

During treatment with AKLIEF, avoid excessive exposure to sunlight, including sunlamps, tanning beds and ultraviolet light. Emphasize the importance of avoiding sun exposure. If exposure to the sun is unavoidable, wear protective clothing over the treated areas and use sunscreen with SPF 15 or higher. What is the tolerability profile of AKLIEF? AKLIEF has a demonstrated safety profile and was generally well tolerated on both the face and trunk.3

• • • • • • •

membranes, abraded skin, open wounds, cuts, eczematous and sunburned skin Avoid use of other dermatologic medications and potentially irritating topical products that have strong skin-drying effect and products with high concentrations of alcohol, astringents, spices, or limes Patients should use non-comedogenic cosmetics Treatment area should not be covered with dressings or bandages Weather extremes, such as wind or cold, may be more irritating Exposure to excessive sunlight, including sunlamps, should be avoided or an effective sunscreen and protective clothing is recommended Certain cutaneous signs and symptoms can be expected with use Use of electrolysis, “waxing” and chemical depilatories for hair removal should be avoided Caution when taking drugs with known photosensitizers

Treatment-emergent adverse events (TEAEs) with incidence ≥1% PREFERRED TERM Number of TEAEs with incidence ≥1% Subjects with any TEAE with incidence ≥1%, n (%)

AKLIEF n= 1220 (%) 297

VEHICLE n= 1200 (%) 140

206 (16.9)

116 (9.7)

General disorders and administration site conditions Application site irritation

84 (6.9)

4 (0.3)

Application site pruritus

29 (2.4)

10 (0.8)


50 (4.1)

56 (4.7)

Upper respiratory tract infection

19 (1.6)

16 (1.3)

Influenza 11 (0.9) Injury, poisoning and procedural complications

18 (1.5)


33 (2.7)

6 (0.5)

Nervous system disorders Headache

16 (1.3)

16 (1.3)

Infections and infestations

Adapted from the Product Monograph.

• Additional adverse reactions that were reported in more than one patient treated with AKLIEF (and at a frequency <1%) included application site pain, skin irritation, application site dryness, application site discoloration, application site rash, application site swelling, application site erosion, acne, dermatitis allergic, and erythema.3 Please see the Product Monograph for complete details on local tolerability signs and symptoms. Longterm (52 weeks) safety and tolerability study3 • In the one-year open label safety study including 453 patients with acne vulgaris of the face and trunk, the pattern of adverse reactions for AKLIEF was similar to that experienced in the 12-week controlled studies. • A total of 12.6% of subjects had at least one adverse reaction during the study, and 2.9% of subjects had an adverse reaction leading to treatment discontinuation. • The most common adverse reactions (≥1% of subjects) for the entire study were application site pruritus (4.6%), application site irritation (4.2%) and sunburn (1.8%). The frequency of adverse reactions decreased over time.

(e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) • Avoid use on chest during breastfeeding • Precaution should be exercised when administering to a nursing mother For more information: Please consult the product monograph at https://pdf.hres.ca/ dpd_pm/00054047.PDF for important information relating to adverse reactions, interactions, and dosing information which have not been discussed in this advertisement. The Product Monograph is also available by calling us at 1-800-467-2081. References 1. Galderma, data on file. 2. Editorial. Br J Dermatol. 2018;179:231-2. 3. AKLIEF® Product Monograph. Galderma Canada Inc. November 25, 2019. 4. Del Rosso JO, et al. A closer look at truncal acne vulgaris: prevalence, severity, and clinical significance. J Drugs Dermatol. 2007;6(6):597-600. AKLIEF® is a registered trademark of Galderma Canada Inc.

This Q&A is published by Ensemble IQ, 20 Eglinton Avenue West, Suite 1800, Toronto, ON M4R 1K8, Telephone: 416-256-9908. No part of this Q&A may be reproduced, in whole or in part, without the written permission of the publisher. © 2020


“People with HS come to the emergency room in severe pain and discomfort requiring assistance with the draining of the boils during a flare-up. It’s not unusual for patients to go home undiagnosed.”



Head of Dermatology, Sunnybrook Hospital

Associate Professor, University of Toronto, Division of General Surgery

“HS is a chronic, painful, inflammatory skin disease that affects 1-4% of the general adult population. It is characterized by boils usually occurring where certain sweat glands are located, such as under the breasts, buttocks, and inner thighs.”


DR. VU KIET TRAN ER physician, University Health Network

“There is currently no cure for HS. Early diagnosis and proper management is important for a patient’s quality of life. The first step for those with HS is to speak to their dermatologist to get an accurate diagnosis.”

North American HS Guidelines NOW AVAILABLE

To learn more about HS from these specialists and the new guidelines, go to www.RecognizingHS.com/PHP


Photo compliments of Dr. Afsaneh Alavi.

ASSESSING PATIENTS WITH RECURRENT BOILS Most HS cases can be recognized with high reliability by the presence of 3 main features:1-3 1. Typical lesions: nodules, sinus tracts, abscesses, scarring 2. Typical anatomical location: axilla, groin, genitals, under the breasts, others (perianal, neck, abdomen, buttocks) 3. Relapses and chronicity: ≥2 times per 6 months

Photo compliments of Dr. Marc Bourcier.

Questions to ask your patients with suspected HS:2 1. Have you had outbreaks of boils during the last 6 months? 2. Where were the boils and how many did you have? To confirm an HS diagnosis, please refer your patient to a dermatologist.

References: 1. Zouboulis CC, et al. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa. JEADV 2015;29:619-44. 2. Lockwood SJ, et al. Diagnostic workup. In: Kimball AB, Jemec GBE, eds. Hidradenitis Suppurativa: A Disease Primer. Cham, Switzerland: Springer; 2016:27-37. 3. Poli F, et al. Clinical presentation. In: Jemec GBE, Revuz J, Leyden JJ, eds. Hidradenitis Suppurativa. Berlin, Germany: Springer; 2006:11-24.

© AbbVie Corporation Printed in Canada HUM/4505A – March 2020

abbvie.ca 1-888-703-3006

November marks

World Antibiotic Awareness Week

Getty Images

to raise awareness about the importance of ensuring that antibiotic use is necessary, safe and effective.


TIMING IS EVERYTHING Understanding the optimal duration of antibiotic therapy for common infections BY SUZANNE SINGH, BScPhm, ACPR, PharmD, RPh


ntimicrobial resistance is one of the biggest threats to global health, including the health of Canadians.(1,2) Each November, the World Health Organization marks World Antibiotic Awareness Week to increase awareness of antimicrobial resistance. The aim is to encourage best practices among the general public, healthcare professionals and policy makers, to avoid the further emergence and spread of antimicrobial resistance.(2) As pharmacists, we have a professional and societal obligation to act. We are trained to identify drug-therapy problems and offer solutions. I have previously written about how pharmacists working in community practices are well-positioned to act as antibiotic stewards.(3) Iâ&#x20AC;&#x2122;ve suggested that pharmacists can help ensure that antibiotics are prescribed appropriately when needed, and only when needed, via the following five strategies: (1) public education, (2) immunization, (3) minor ailment assessment,

[Vol.7 No.9] NOVEMBER 2020


(4) prescribing optimization and (5) effective antibiotic counselling. This article embarks on a deeper dive into one of the components of prescribing optimization—optimizing the duration of antibiotic treatment for common infections in the community.

Excessive duration of therapy: a form of antibiotic overprescribing

Pharmacists should be aware of three categories of antibiotic overprescribing.(3) The first category is using an antibiotic when one is not likely to be beneficial. Most clinicians are familiar with this type of antibiotic overuse. In fact, it has been established in the literature that antibiotics prescriptions are commonly unnecessary in the community. For example, evidence suggests that antibiotics are overprescribed in upper respiratory tract infections, with an estimated 30%–50% of antibiotics prescribed judged to be unnecessary, and elderly patients being most likely to receive a prescription.(4,5) The second category of overprescribing is prescribing a broad-spectrum antibiotic when a narrow-spectrum agent will do. I explain this category of unnecessary antibiotic prescribing using the expression “do not use a cannon to kill a mosquito.” Empirical use of broad-spectrum antibiotics increases, by selection, the prevalence of bacteria resistant to several antibiotics. Finally, the third category of overprescribing, the focus of this article, is prescribing an antibiotic for an excessive period of time. A study of primary care prescribers from the United Kingdom concluded that for most common infections treated in primary care, a substantial proportion of antibiotic prescriptions have durations exceeding those recommended in guidelines.(6) Research conducted by Public Health Ontario (PHO) found that the median duration of antibiotic regimes prescribed by Ontario family physicians was seven to eight days (38%), with less than

For most common infections treated in primary care, a substantial proportion of antibiotic prescriptions have durations exceeding those recommended in guidelines.


NOVEMBER 2020 [Vol.7 No.9]

25% of prescriptions prescribed for shorter than seven days, and 35% of antibiotic courses prescribed for longer than eight days.(7) PHO also observed considerable variability in prescribed antibiotic duration across family physicians, with greater use of prolonged antibiotic courses associated with later physician career stage, rural location and a large pediatric practice.(7) The reality is that shorter durations of antibiotic treatment courses are often supported by evidence, but not necessarily adopted by prescribers.(8-10) We should not be exposing our patients to excessive antibiotics, and pharmacists can (and should) influence decisions about optimal treatment durations.

Risks of excessive durations of antibiotics: every day matters for every patient

A scan of the literature identifies several studies which highlight that even one extra day of antibiotics can be harmful to patients. One retrospective UK study showed that patients hospitalized for community-acquired pneumonia had a 9% risk of Clostridium difficile per day, with longer durations of antibiotics being a contributing factor.(11) Other studies in hospitalized patients have also demonstrated a relationship between longer duration of antibiotic use and emergence of drug resistance.(12-14) In addition to the collateral ecological damage of antibiotics, such as C. difficile and drug resistance, the other risks of antibiotics are worth a reminder. The spectrum of harm that can result from antibiotics ranges from side effects, such as nausea, vomiting, diarrhea and yeast infections, that may adversely impact a patient’s quality of life, to more serious risks. Some of these risks can be drug or drug-class specific. A few examples of safety concerns include the risk of tendon rupture with fluoroquinolones; the risk of QT prolongation with fluoroquinolone and macrolide drug interactions; and the risk of hyperkalemia with trimethoprim–sulfamethoxazole when used with drugs that also increase potassium, such as angiotensinconverting enzyme inhibitors, angiotensin-II receptor blockers and potassium-sparing diuretics.(3) Evidence suggests that antibiotics are frequently implicated in adverse drug reactions that lead to emergency room visits.(15) The key message is that every extra day counts when it comes to exposing patients to antibiotic harms.

“Guidelinitis” and the lack of standardization in antibiotic treatment durations

Recommended treatment durations for common community infections should be found fairly easily in clinical practice guidelines, right? If one asked where to find the Canadian guidelines for how to treat [insert common community infection here], in truth, the answer to that question may be somewhat complicated and may require successive computer clicks. We have seen other jurisdictions, such as the United Kingdom, tackle the development of national guidelines for common community infections, with a lens of antibiotic stewardship. The UK’s National Institute for Health and Care Excellence (NICE) has produced guidance and quality standards for antibiotic use in the community.(16) Canada seems to lag behind in this regard.(1) In the absence of a “standard place to look” to find Canadian guidelines on community infections, clinicians are challenged to review multiple sources to hunt down answers. The phenomenon of “guidelinitis” has been used in the literature to describe the predicament clinicians may face when there are

multiple guidelines on a single topic, potentially with conflicting and/or faulty recommendations.(17) This is certainly relevant to the discussion around how best practices are determined and possible reasons to explain variations in practice.(17) When recommendations from various sources are not aligned or up to date, clinicians may be left to use their own judgments around best practices for antibiotic prescribing, of which treatment duration is one. Perhaps this may partly explain why practitioners gravitate towards using a default of “7 days” for most antibiotic prescriptions; while simplistic, it might very well be unrealistic to expect busy practitioners to curate the available literature. I, myself, struggle with finding time to critically appraise clinical practice guidelines or look into the primary literature from which guidelines are derived. I access a number of resources when caring for my patients and working with my primary care team to help navigate antibiotic prescribing decisions. These resources include, but are not limited to, guidance from organizations such as the Infectious Diseases Society of America (IDSA), the Public Health Agency of Canada (PHAC), Public Health Ontario (PHO) and various specialist organizations. In Ontario, one notable resource is the Anti-infective Guidelines for Community Acquired Infections (~$30), published by the academic detailing group, MUMS Health.(18) This popular resource is commonly referred to by primary care practitioners simply as “the orange book,” which designates the colour of the book’s cover, although this resource is also available in App format. Similarly, Bugs & Drugs (free online) is likely recognizable to Albertans and beyond, and the Saskatchewan-based academic detailing group of RxFiles has also done some important work on antibiotic stewardship in primary care.(19,20) At a local level, I periodically access resources from my hospital’s antibiotic stewardship program.(21) I would encourage practitioners to familiarize themselves with these available resources so they can be better equipped to support effective antibiotic use.

Antibiotic treatment durations for common infections: a brief guide There can be problems with treating bacterial infections with either too long or too short of a course of antibiotics. Problems with treating for too short a period may include therapeutic failure, relapse and selecting resistance for pathogenic bacteria. Problems with treating for too prolonged a course may include adverse effects, such as C. difficile and developing drug resistance; the risk of patient nonadherence with a longer course of treatment; and an increased financial cost to the patient or healthcare system. I’ve attempted to summarize current recommendations for antibiotic treatment durations for common infections (Table 1) based on my review of the literature.(22-34) This table is essentially “the money shot” for this article! Review it carefully. As a general summary, for acute uncomplicated cystitis, nitrofurantoin is typically administered for five days, trimethoprim–sulfamethoxazole or quinolones for three days, and fosfomycin for one day. When antibiotics are indicated for infections such as acute bacterial rhinosinusitis, cellulitis, community-acquired pneumonia or acute exacerbations of chronic obstructive pulmonary disease, typically five to seven days of treatment is sufficient; 10 days of treatment is usually recommended for pharyngitis due to Group A streptococcus.


Antibiotic treatment durations for common community infections in adults (IF antibiotics are indicated*)(22-34) Condition

Treatment Duration

Community-acquired pneumonia

5–7 days(22,23)

Acute bacterial rhinosinusitis

5–7 days(24) 10 days(25)


Uncomplicated: 5 days(26, 27) Complicated: 7–10 days(26,27)

Chronic obstructive pulmonary disease (COPD) exacerbation Acute uncomplicated cystitis

Pharyngitis due to Group A streptococcus

5–7 days(28-30) 5 days for nitrofurantoin(31-33) 3 days for trimethoprim– sulfamethoxazole or quinolones(31-33) 1 day for fosfomycin(31-33) 10 days(34)

* This applies once a clinical decision has been made that an antibiotic is, in fact, indicated. The scope of this article does not include a discussion on when antibiotics are and are not indicated for the selected clinical condition; for example, the use of antibiotics in COPD exacerbations is controversial.(28-30)

Balancing the long and the short of antibiotic durations: pointers for practice

So, you’ve read this entire article. How are you going to use what you’ve read here in your daily clinical practice? To help you, I will discuss three practical questions that often come up in practice.

Practice Question 1: Can an antibiotic be stopped before its full treatment course if a patient is “feeling better”? There is some thought that continuing antibiotics past resolution of symptoms for acute bacterial infections does not afford any benefits and probably selects for antibiotic resistance.(35) If patients feel substantially better with resolution of symptoms of infection, a reasonable approach may be to advise them to contact their clinician to determine whether the antibiotic can be stopped. This requires clinicians to be receptive to the concept of “antibiotic deprescribing” and not fear customizing duration of therapy on a patient-specific basis.

Practice Question 2: Should a pharmacist contact a prescriber to cut back on the days’ supply quantity if the pharmacist feels the antibiotic is being prescribed for an excessive duration? Can or should the pharmacist do so within their own scope? This is an interesting predicament. Consider this scenario. You are a pharmacist caring for an adult patient who presents to your pharmacy with a prescription for amoxicillin 500 mg three times daily for 14 days. Upon questioning the patient, you deduce that they are likely being treated for uncomplicated acute bacterial rhinosinusitis. You review the 2014 Canadian guidelines which state a 10-day course of amoxicillin is suggested.(25) You take a look at the 2012 IDSA guidelines that suggest a five- to sevenday treatment course would suffice.(24) Notwithstanding that the treatment durations differ, neither of these guidelines suggest a 14-day treatment course would be appropriate.

(continued on page 29)

[Vol.7 No.9] NOVEMBER 2020



DEMONSTRATED TO TREAT MULTIPLE SYMPTOMS OF MDD2 Depressive symptoms (MADRS total score) Demonstrated 60% improvement from baseline at 8 weeks with Trintellix 20 mg vs 37% with placebo (-18.8 vs -11.7, p<0.0001)1,2*†

Overall function (SDS) Demonstrated improvement from baseline at 8 weeks with Trintellix 20 mg vs placebo: Up to 87% improvement in overall function (-8.4 vs -4.5, p=0.0005)1*† Up to 86% improvement in function at work (-2.6 vs -1.4, p=0.0059)1*† Up to 82% improvement in function at home (-3.1 vs -1.7, p<0.0001)1*† Up to 82% improvement in function in a social setting (-3.1 vs -1.7, p<0.0001)1*† † The starting and recommended dose of Trintellix is 10 mg once daily for adults <65 years of age. See the Product Monograph for complete dosing and administration information. Pr

Trintellix® (vortioxetine) is indicated for the treatment of MDD in adults.2

MADRS=Montgomery-Åsberg Depression Rating Scale; MDD=major depressive disorder; SDS=Sheehan Disability Scale

Clinical use: Efficacy in providing symptomatic relief of MDD demonstrated in trials of up to 8 weeks’ duration; efficacy in maintaining an antidepressant response demonstrated for up to 24 weeks. Physicians who elect to use Trintellix for extended periods should periodically re-evaluate the usefulness of the drug for individual patients. Not indicated in patients <18 years of age.

I would encourage pharmacists to implement an antibiotic callback system, where patients would be contacted routinely on Day 3 of antibiotic treatment to follow up on their clinical status and asssess for any safety concerns.

Contraindication: • Combined use with monoamine oxidase inhibitors (MAOIs) Most serious warnings and precautions: • Potential association with behavioural and emotional changes, including self-harm: Severe agitation type events reported; rigorous clinical monitoring for suicidal ideation or other indicators of potential for suicidal behaviour is advised in patients of all ages; this includes monitoring for agitation-type emotional and behavioural changes • Discontinuation symptoms: Gradual reduction in dose, rather than abrupt cessation, is recommended Other relevant warnings and precautions: • Bone fracture risk pressure or narrow angle glaucoma • Abnormal bleeding • Caution in patients with a • Caution in moderate history of mania/hypomania hepatic impairment; not and discontinue use in any recommended in severe patient entering a manic phase hepatic impairment • Caution with concurrent • Caution in patients who use of electroconvulsive have a history of seizures or therapy (ECT) in patients with unstable • Dependence/tolerance epilepsy • Serotonin syndrome/ • Hyponatremia neuroleptic malignant • Caution in patients with syndrome severe renal insufficiency • Cognitive and motor • Not recommended during disturbances breastfeeding • May cause mydriasis; • Dosage adjustment in caution in patients with elderly patients raised intraocular

In my opinion, this presents a wonderful teachable moment for the pharmacist to educate both the prescriber as well as the patient about the risks of excessive antibiotic exposure. In this scenario, it may be worth a phone call or fax to the prescriber to review current best practices. Irrespective of the antibiotic treatment duration prescribed, I would encourage pharmacists to implement an antibiotic callback system, where patients would be contacted routinely on Day 3 of antibiotic treatment to follow up on their clinical status and assess for any safety concerns.(36,37) This follow-up may trigger a collaborative opportunity with a prescriber. For example, if a prescriber wanted to stick with prescribing a 14-day treatment course for acute bacterial rhinosinusitis initially, but the patient has improved after Day 3, the prescriber may feel more comfortable accepting the pharmacist’s suggestion to shorten that antibiotic course to five days.

For more information: Consult the Product Monograph at www.trintellixmonograph.ca for important information about contraindications, warnings, precautions, adverse reactions, interactions, dosing instructions and conditions of clinical use not discussed in this piece. The Product Monograph is also available by calling 1-800-586-2325. DSM=Diagnostic and Statistical Manual of Mental Disorders; MADRS=Montgomery-Åsberg Depression Rating Scale; MDD=major depressive disorder; MDE=major depressive episode; SDS=Sheehan Disability Scale * Double-blind, fixed-dose, placebo-controlled study of 608 patients aged 18-75 years with a primary diagnosis of recurrent MDD according to DSM-IV-TR criteria, a current MDE >3 months’ duration and a MADRS total score ≥26. Patients were randomized to Trintellix 15 mg, 20 mg (10 mg/day during Week 1 and 15 or 20 mg/day from Weeks 2 to 8) or placebo for 8 weeks. Mean baseline MADRS total scores were 31.5 for placebo, 31.8 for Trintellix 15 mg and 31.2 for Trintellix 20 mg. Mean baseline SDS total scores were 19.8 for placebo, 20.6 for Trintellix 15 mg and 20.7 for Trintellix 20 mg. Mean baseline SDS work scores were 6.3 for placebo, 6.8 for Trintellix 15 mg and 6.9 for Trintellix 20 mg. Mean baseline SDS social scores were 6.8 for placebo, 6.9 for Trintellix 15 mg and 6.8 for Trintellix 20 mg. Mean baseline SDS family scores were 6.9 for placebo, 6.7 for Trintellix 15 mg and 7.0 for Trintellix 20 mg.1,2

Practice Question 3: Should pharmacists abandon the practice of counselling patients to complete their antibiotic course and “take until finished”? A final word about conventional advice to complete the course of antibiotics. Historically, many of us were trained to counsel patients to complete their course of antibiotics. In fact, this messaging is also seen in some public health campaigns about antibiotic awareness. When one examines the rationale behind this advice, it appears that the evidence to support this mantra of “take until finished” is predicated on a myth that completing antibiotics too early may increase the risk of antibiotic resistance.(38)

References: 1. Boulenger JP, et al. Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder. Int Clin Psychopharmacol 2014;29(3):138-49. 2. Trintellix Product Monograph. Lundbeck Canada Inc., April 15, 2019. Trintellix ® is a registered trademark of H. Lundbeck A/S, used under license by Lundbeck Canada Inc.

(continued on page 30)

[Vol.7 No.9] NOVEMBER 2020


Indeed, formulaic approaches to antibiotic advice can be problematic. Pharmacists will need to become more comfortable in understanding the nuances around antibiotic prescribing durations, if we are truly going to embrace our role as antibiotic stewards. I would challenge pharmacists to avoid affixing the classic “Take until finished” auxiliary label on all antibiotic vials, as we’ve been trained to do. The use of this auxiliary label may in fact require careful thought. For example, it may be appropriate to indicate “Take until finished” for a patient taking a threeday antibiotic course for acute uncomplicated cystitis, but the auxiliary label should not be automatically placed on the vial of an antibiotic that may be appropriately reassessed earlier than the prescribed completion date.


The World Health Organization’s campaign on antimicrobial resistance includes the slogan “Antibiotics: Handle With Care.”(2) As we mark World Antibiotic Awareness Week this November, we have an opportunity to raise awareness among the public and stakeholders about the importance of ensuring that antibiotic use is necessary, safe and effective. It is of public health importance that we showcase the unique role that pharmacists have in facilitating appropriate antibiotic decision-making. To slow the progression of antibiotic-resistant bacteria, all healthcare professionals must strengthen their efforts to address this issue. Pharmacists have a responsibility to assist in the war on antibiotic resistance as stewards in each healthcare setting, especially in the outpatient setting where most antibiotics are prescribed. Pharmacists need to routinely assess whether patients may be exposed to antibiotics unnecessarily. Part of this assessment includes ensuring that the course of antibiotics is not too long, not too short, and just right. Suzanne Singh (suzanne.singh@sinaihealth.ca) is a pharmacist with the Mount Sinai Academic Family Health Team in Toronto, ON and an adjunct lecturer at the Department of Family and Community Medicine, University of Toronto. She is a strong advocate for enhancing the role of the pharmacist within integrated and innovative primary care practice models. REFERENCES

1. Chief Public Health Officer of Canada’s 2019 spotlight report. Rx handle with care: preserving antibiotics now and into the future. June 2019. https://www.canada.ca/ content/dam/phac-aspc/documents/corporate/publications/chief-public-healthofficer-reports-state-public-health-canada/preserving-antibiotics/Final_CPHO_ Report_EN_June6_2019.pdf (accessed May 1, 2020). 2. World Health Organization. World Antibiotic Awareness Week. http://www.who.int/ campaigns/world-antibiotic-awareness-week/en/ (accessed May 1, 2020). 3. Singh S. Attack of the superbugs. Battle tactics pharmacists may use to combat antimicrobial resistance. Pharm Pract Business 2018;5(12):23-6. https://www. canadianhealthcarenetwork.ca/pharmacists/clinical/health-index-therapeutics/ infectious-diseases/battle-tactics-pharmacists-may-use-to-combat-antimicrobialresistance-43583 (accessed May 1, 2020). 4. Fleming-Dutra KE, Hersh AL, Shapiro DJ et al. Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011. JAMA 2016;315:1864-73. 5. Silverman M, Povitz M, Sontrop JM, et al. Antibiotic prescribing for nonbacterial acute upper respiratory infections in elderly persons. Ann Intern Med 2017;166:765-74. 6. Pouwels KB, Hopkins S, Llewelyn MJ, et al. Duration of antibiotic treatment for common infections in English primary care: cross sectional analysis and comparison with guidelines. BMJ 2019;364:l440. 7. Fernandez-Lazaro CI, Brown KA, Langford BJ, et al. Late-career physicians prescribe longer courses of antibiotics. Clin Infect Dis 2019;69:1467-75. 8. Spellberg B. The new antibiotic mantra: shorter is better. JAMA Intern Med 2016;176:1254-5. 9. Wald-Dickler N, Spellberg B. Short-course antibiotic therapy-replacing constantine units with “shorter is better”. Clin Infect Dis 2019;69:1476-9. 10. Kim DK, Kim JH, Lee JY, et al. Reappraisal of the treatment duration of antibiotic regimens for acute uncomplicated cystitis in adult women: a systematic review and network meta-analysis of 61 randomised clinical trials. Lancet Infect Dis 2020; doi:10.1016/S1473-3099(20)30121-3. 30

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11. Chalmers JD, Akram AR, Singanayagam A, et al. Risk factors for Clostridium difficile infection in hospitalized patients with community-acquired pneumonia. J Infect 2016;73:45-53. 12. Nasrin D, Collignon PJ, Roberts L, et al. Effect of beta lactam antibiotic use in children on pneumococcal resistance to penicillin: prospective cohort study. BMJ 2002;324:28-30. 13. Teshome BF, Vouri SM, Hampton N, et al. Duration of exposure to antipseudomonal β-lactam antibiotics in the critically ill and development of new resistance. Pharmacotherapy 2019;39:261-70. 14. Vaughn VM, Flanders SA, Snyder A, et al. Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: a multihospital cohort study. Ann Intern Med 2019;171:153-63. 15. Shehab N, Lovegrove MC, Geller AI, et al. US emergency department visits for outpatient adverse drug events, 2013-2014. JAMA 2016;316:2115-25. 16. National Institute for Health and Care Excellence. Antibiotic use. https://www. nice.org.uk/guidance/conditions-and-diseases/infections/antibiotic-use (accessed May 1, 2020). 17. Johnston BL, Conly JM. Guidelinitis: a new syndrome? Can J Infect Dis 2000;11:299-303. 18. MUMS Health. 2019 Anti-infective guidelines for community-acquired infections. https://www.mumshealth.com/guidelines-tools/anti-infective (accessed May 1, 2020). 19. Alberta Health Services. Bugs & drugs. www.bugsanddrugs.org/ (accessed May 1, 2020). 20. RxFiles. Antibiotic stewardship & awareness: links public information / patient resources. www.rxfiles.ca/rxfiles/uploads/documents/RxFiles-ABX-Public.htm (accessed May 1, 2020). 21. Sinai Health System - University Health Network Antimicrobial Stewardship Program. https://www.antimicrobialstewardship.com/ (accessed May 1, 2020). 22. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med 2019;200:e45-67. 23. Sinai Health System - University Health Network Antimicrobial Stewardship Program. Community-acquired pneumonia. https://www.antimicrobialstewardship. com/community-acquired-pneumonia (accessed May 1, 2020). 24. Chow AW, Benninger MS, Brook I, et al. Infectious Diseases Society of America. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis 2012;54:e72-112. 25. Kaplan A. Canadian guidelines for acute bacterial rhinosinusitis. Can Fam Physician 2014;60:227-34. https://www.cfp.ca/content/cfp/60/3/227.full.pdf (accessed May 1, 2020). 26. Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014;59:e10-52. 27. Sinai Health System - University Health Network Antimicrobial Stewardship Program. Cellulitis. https://www.antimicrobialstewardship.com/ssisummary (accessed May 1, 2020). 28. Wedzicha JA, Miravitlles M, Hurst JR, et al. Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J 2017;49(3):1600791. 29. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive lung disease. 2020 Report. https://goldcopd.org/wp-content/uploads/2019/12/GOLD-2020-FINALver1.2-03Dec19_WMV.pdf (accessed May 1, 2020). 30. Sinai Health System - University Health Network Antimicrobial Stewardship Program. Acute exacerbation of COPD. https://www.antimicrobialstewardship.com/ aecopd (accessed May 1, 2020). 31. Mazzulli T. Diagnosis and management of simple and complicated urinary tract infections (UTIs). Can J Urol 2012;19(Suppl 1):42-8. 32. Beahm NP, Nicolle LE, Bursey A, et al. The assessment and management of urinary tract infections in adults: guidelines for pharmacists. Can Pharm J 2017;150:298-305. 33. Gupta K, Hooton TM, Naber KG, et al. Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52:e103-20. 34. Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis 2012;55:1279-82. 35. Llewelyn MJ, Fitzpatrick JM, Darwin E, et al. The antibiotic course has had its day. BMJ 2017;358:j3418. https://www.bmj.com/content/358/bmj.j3418 (accessed August 12, 2020). 36. Westfall GR, Narducci WA. A community-pharmacy-based callback program for antibiotic therapy. J Am Pharm Assoc 1997;NS37:330-4. 37. Beaucage K, Lachance-Demers H, Ngo TT, et al. Telephone follow-up of patients receiving antibiotic prescriptions from community pharmacies. Am J Health Syst Pharm 2006;63:557-63. 38. Langford BJ, Morris AM. Is it time to stop counselling patients to “finish the course of antibiotics”? Can Pharm J 2017;150:349-50.

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A primer on common ailments managed by nonprescription products




CC, a healthy 23-year-old male, presents to your pharmacy with a printed postop sheet from his dentist. It provides instructions on post-procedure pain relief (regular strength ibuprofen or extra strength acetaminophen, taken according to OTC product labelling) and oral hygiene (antibacterial mouthwash). You learn that CC had a damaged tooth extracted yesterday. He is complaining about the pain, although itâ&#x20AC;&#x2122;s not severe and has no red flag features. Neither ibuprofen nor acetaminophen has provided adequate pain relief. CC is wondering if there is anything else he can try or if he should contact his dentist for a prescription. He was prescribed Tylenol No. 3 following a previous extraction and found this worked well. CC has no medical conditions or allergies, and is not taking any medications. He consumes alcohol occasionally and does not smoke.


Oral pain affects a large number of Canadians. In fact, 11.7% of 5,284 survey respondents reported experiencing mouth pain in the past 12 months.(1) Oral pain is significantly more prevalent among 32

There is growing evidence that combining simple analgesics, namely acetaminophen and ibuprofen, provides greater acute dental pain relief than either analgesic alone. adolescents and younger adults, those in lower income groups, those who avoided a dental professional because of cost, and those with untreated tooth decay.(1) The most common forms of oral pain are acute in nature and can result from pathological conditions or disorders related to somatic and neurological structures.(2) Pain can be attributed to conditions affecting the hard tissues (e.g., caries of enamel, dentine) or those affecting soft tissue and supporting bone (e.g., gingivitis, periodontitis), some of which may necessitate dental intervention.(2) Table 1 outlines traditional analgesic regimens for managing postprocedural dental pain. Dental interventions anticipated to cause mild pain include frenectomies and simple extractions (e.g., removal of visible

NOVEMBER 2020 [Vol.7 No.9]


tooth); those expected to cause moderate pain include implant surgeries and surgical extractions; and interventions predicted to cause severe pain include partial or full bony impaction surgeries and periodontal surgeries.(3)

Case analysis

Despite the large number of nonprescription products marketed for pain and fever, most consist of one of four active ingredients: acetaminophen, acetylsalicylic acid, ibuprofen or naproxen. However, there is growing evidence that combining simple analgesics, namely acetaminophen and ibuprofen, provides greater acute dental pain relief than either analgesic alone.(4-6) For example, one randomized controlled trial of 408 adults experiencing moderate to severe pain after surgical removal of impacted third molars, showed that a fixed-dose combination product of acetaminophen 975 mg and ibuprofen 292.5 mg/day provided significantly superior analgesia over equivalent daily monotherapy doses of either ingredient alone in the initial 48-hours after extraction. More specifically, the fixeddose combination provided a significantly shorter onset of meaningful pain relief, reduced the consumption of opioid rescue medication, and lowered maximum pain scores. This was achieved without compromising the well-established safety profile of either active constituent.(6) Simple analgesics may also have equivalent or superior efficacy when compared with opioids for postextraction dental pain; as such, routine opioid prescribing for post-extraction dental pain must be questioned because of the potential morbidity and longterm consequences of opioid use.(7,8) Evidence suggests that for opioid-naĂŻve patients, filling a prescription for an opioid pain medication following tooth extraction is associated with a greater risk of ongoing persistent opioid use.(7) Multimodal analgesia (i.e., combining medications with different mechanisms of action) is often recommended as an alternative to opioids for acute dental


OTC Issues

pain.(6) Combining simple analgesics, in particular, may offer effective pain relief while causing fewer acute adverse events than opioid-containing alternatives. In 2019, Health Canada approved Combogesic—the first nonprescription fixed-dose combination of simple analgesics. This product contains acetaminophen 325 mg and ibuprofen 97.5 mg per tablet and is indicated for the treatment of acute mild to moderate pain in adults. Acetaminophen is believed to act by inhibiting cyclooxygenase (COX) (and subsequent prostaglandin synthesis) within the central nervous system and via activation of central serotonergic pathways. Ibuprofen, on the other hand, is a traditional nonsteroidal anti-inflammatory drug (NSAID) that decreases the synthesis of pain and inflammatory-promoting prostaglandins via nonselective inhibition of COX-1 and COX-2. Note, however, that the antiinflammatory activity of ibuprofen is considered negligible at self-care doses.(9) The introduction of Combogesic may provide impetus for updating current guidelines on the management of postprocedural dental pain. Traditionally, the combination of acetaminophen and ibuprofen has been reserved for dental interventions causing moderate to severe pain (Table 1). However, Combogesic’s indication for acute mild to moderate pain challenges this recommendation and suggests utility in less severe cases of dental pain. Changes to recommendations may

DID YOU KNOW… Combogesic is also indicated for the reduction of fever in adults and can be used for this purpose for up to three days (without further assessment by an appropriate healthcare provider). However, to date, findings of superiority relative to ibuprofen or acetaminophen alone are limited to dental pain in adults. As such, Combogesic’s efficacy may not be generalizable to other indications (including fever), other types of pain, or other patient populations. Pharmacists must exercise their professional judgment when considering Combogesic use for indications and populations that lack published evidence.


Traditional Analgesic Regimens According to Dental Pain Severity(3,4,11,12) Anticipated Pain Severity

Oral Analgesic Options


Ibuprofen 200–400 mg q4–6h prn pain OR Acetaminophen 500–1000 mg q4–6h prn pain

Mild to Moderate

Ibuprofen 400–600 mg q6h (fixed interval) for 24 hours then Ibuprofen 400 mg q4–6h prn pain OR Acetaminophen 1000 mg q6h (fixed interval) for 24 hours then Acetaminophen 500–1000 mg q4–6h prn pain

Moderate to Severe

Ibuprofen 400–600 mg plus Acetaminophen 500–1000 mg q6h (fixed interval) for 24 hours then Ibuprofen 400 mg plus Acetaminophen 500–1000 mg q6h prn pain


Ibuprofen 400–600 mg plus Acetaminophen 650 mg plus Opioid (Codeine 30–60 mg or Oxycodone 5–10mg) q6h (fixed interval) for 24 hours then Ibuprofen 400–600 mg plus Acetaminophen 500–1000 mg q6h prn pain NOTE: If an opioid is necessary, codeine should be considered first; if insufficient, oxycodone may be considered.(11)

also be on the horizon for more severe postprocedural dental pain with the approval of higher-strength nonprescription combination analgesics such as Advil Dual Action (containing ibuprofen 250 mg and acetaminophen 500 mg) in the United States.(10) At a minimum, the introduction of nonprescription combination analgesics offers convenient formulations for achieving multimodal analgesia when indicated.


Removal of a damaged tooth is considered a simple extraction and is anticipated to cause mild pain. CC may take one or two Combogesic tablets every six hours. If his pain does not respond to two tablets, three tablets may be taken at subsequent doses, if advised by his dentist. The maximum recommended dose for acute pain is 12 tablets over a 24-hour period for no more than five days (without further assessment by an appropriate healthcare provider). CC should be warned to avoid taking this product with other acetaminophen- or ibuprofen-containing products. Counsel CC about the adverse effects associated with the combination product (which are similar to those of the individual drug components).(4) Follow up with CC within 72 hours to ensure adequate pain relief and that no alarming signs or symptoms have emerged. Note: Combogesic is expected to be available in late 2020/early 2021.


1. Ravaghi V, Quinonez C, Allison PJ. Oral pain and its covariates: findings of a Canadian population-based study. J Can Dent Assoc 2013;79:d3. 2. Renton T. Dental (odontogenic) pain. Rev Pain 2011;5(1):2-7. 3. Hersh EV, Kane WT, O’Neil MG, et al. Prescribing recommendations for the treatment of acute pain in dentistry. Compend Contin Educ Dent 2011;32(3):22, 24-30. 4. Moore PA, Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after thirdmolar extractions: translating clinical research to dental practice. J Am Dent Assoc 2013;144:898-908. 5. Moore PA, Ziegler KM, Lipman RD, et al. Benefits and harms associated with analgesic medications used in the management of acute dental pain: an overview of systematic reviews. J Am Dent Assoc 2018;149:256-5. 6. Daniels SE, Atkinson HC, Stanescu I, et al. Analgesic efficacy of an acetaminophen/ibuprofen fixed-dose combination in moderate to severe postoperative dental pain: a randomized, double-blind, parallel-group, placebo-controlled trial. Clin Ther 2018;40:1765-76. 7. Harbaugh CM, Nalliah RP, Hu HM, et al. Persistent opioid use after wisdom tooth extraction. JAMA 2018;320:504-6. 8. Moore PA, Dionne RA, Cooper SA, et al. Why do we prescribe Vicodin? J Am Dent Assoc 2016;147:530-3. 9. Bradley JD, Brandt KD, Katz BP, et al. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee. N Engl J Med 1991;325:87-91. 10. American Pharmacists Association. FDA approves combination ibuprofen-acetaminophen drug for U.S. Updated March 6, 2020. https://www.pharmacist. com/article/fda-approves-combination-ibuprofenacetaminophen-drug-us (accessed August 30, 2020). 11. Haas DA. An update on analgesics for the management of acute postoperative dental pain. J Can Dent Assoc 2002;68:476-82. 12. American Dental Association. Oral health topics. Oral analgesics for acute dental pain. Updated August 28, 2019. https://www.ada.org/en/member-center/oralhealth-topics/oral-analgesics-for-acute-dental-pain (accessed August 30, 2020).

Nardine Nakhla is a practising community pharmacist and a faculty member at the University of Waterloo School of Pharmacy. The author thanks Kristi Butt, PharmD, for her contribution to this article.

[Vol.7 No.9] NOVEMBER 2020



Preventing the flu is your choice. In a study of 31,000 people over 65 in the US and Canada, FLUZONE® High-Dose was demonstrated to be

24% MORE EFFECTIVE than our standard dose vaccine* in protecting seniors from the flu. If you’re 65+, vaccination is one of the best ways to protect yourself from the flu. Ask your healthcare provider for the FLUZONE® High-Dose flu shot and get protected now.

*Vs. standard dose FLUZONE® vaccine against laboratory-confirmed influenza caused by any viral type or subtype.


FLUZONE® High-Dose is a vaccine used to prevent influenza in adults 65 years of age and older. Influenza (or flu) is an infection caused by the influenza virus. Annual vaccination using the current vaccine is recommended for prevention against influenza as immunity declines in the year following vaccination. Persons with a history of severe allergic reaction to eggs or egg products or any component of FLUZONE® High-Dose should not receive the vaccine. FLUZONE® High-Dose will only protect against the strains of influenza virus contained in the vaccine or those that are closely related. FLUZONE® High-Dose will not protect against any other strains of influenza virus. FLUZONE® High-Dose is not indicated for the prevention of hospitalization or death after the onset of disease. As with all vaccines, FLUZONE® High-Dose does not protect 100% of people immunized. Allergic reactions can occur. The most common side effects are pain at the injection site and muscle ache. Contact your healthcare provider to see if this vaccine is right for you. For more information, visit www.sanofi.ca. FLUZONE® is a trademark of Sanofi Pasteur. Sanofi Pasteur 1755 Steeles Avenue West, Toronto, Ontario M2R 3T4 © 2019 Sanofi Pasteur Limited. All rights reserved. DIN: 02445646 SPCA.FLHD.18.06.0031

OTC Counselling Tips

A series of tip sheets created by final-year pharmacy students at the University of Waterloo

“B” HEALTHY: VITAMIN B12 DEFICIENCY IN RECURRENT APHTHOUS ULCERS Vitamin B12 is used by the body for protein and carbohydrate synthesis.(1) Vitamin B12 deficiencies in Canada are rare, but have several different causes and sequelae. Among these sequelae is recurrent aphthous ulceration from diminished mucosal repair.(1) / BY ANDREW SAV0

What are aphthous ulcers?(1-3)

Prevalence of aphthous ulcers is as high as

• Aphthous ulcers, also known as canker sores, are inflammatory lesions of the oral mucosa.



•  Associated problems include pain, difficulty eating or talking, and decreased quality of life. •  Possible causes include stress, mucosal damage, some medications, SLS (sodium lauryl sulfate), some foods (e.g. spicy, acidic food), genetic factors or vitamin deficiencies.




Within 3 months, recurrence rates are as high as



It’s been hypothesized that YOUNG ADULTS more often get canker sores due to their less nutritious diets, leading to vitamin deficiencies. Several vitamin deficiencies, especially vitamin B12, are thought to contribute to recurrent aphthous ulcers.(1) A potential mechanism for this is decreased nucleotide and macromolecule synthesis and subsequent reduced ability to repair the mucosa.(1)

If there is no improvement after 6 months of vitamin B12 supplementation, refer to a physician. It may be herpetiform ulceration, Behçet syndrome, systemic lupus erythematosus, irritable bowel disease or something else!(2,4) (continued on page 36) Andrew Savo is in his final year of the PharmD program at the University of Waterloo School of Pharmacy. He loves learning about infectious diseases and mental health, and hopes to obtain a career with an emphasis in one of these areas.

[Vol.7 No.9] NOVEMBER 2020


(OTC Counselling Tips continued)

Vitamin B12 CASE STUDY


One case study has shown that in patients with low B12 levels and recurrent aphthous ulcers, normalizing B12 levels led to no recurrences at least 6 months later.(6)

In a randomized clinical trial, 74% of patients treated with sublingual vitamin B12 1000 mcg daily had no recurrent ulcers after 6 months compared with 32% of patients in the placebo arm (p<0.01), regardless of B12 levels.(7)

Assessing diet may be useful in making the decision to treat with B12 especially in vegan patients.(6,8) Remind patients to let sublingual B12 dissolve under the tongue for a couple of minutes (do not chew or swallow it).

“B” HELPFUL(3,5)

While considering etiology, don’t forget to address the patient’s pain! Try topical protectants, avoid NSAIDs.


Aphthous ulcers will often recur within weeks to months following recovery. Taking the time to help patients prevent recurrences shows them you care.

Aphthous ulcers can be prevented by remembering and implementing this simple mnemonic: CANKER (1,4,7) CARE for your mouth—brush teeth regularly AVOID acidic, spicy, salty foods NO SLS, an ingredient in some toothpastes KEEP chips and other mouth-damaging foods away


Other signs and symptoms of vitamin B12 deficiency might help guide you: Fatigue

Vegan diet


EAT foods rich in vitamin B12 or use supplements REDUCE stress—meditation, focused breathing and guided imagery may help, though these measures have not been directly studied in aphthous ulcer prevention

Let’s “B” smart

All patients with recurrent aphthous ulcers should be screened for symptoms and likelihood of vitamin B12 deficiency. Some evidence shows supplementation to be useful regardless of vitamin B12 levels, so it is reasonable to recommend B12 supplementation in patients suspected of having low levels.(7)

“B” CAREFUL(3,4)

Some red flags that may warrant referral include: Impaired eating

>5 ulcers

Ulcers >1 cm in diameter


Ulcers lasting longer than 14 days Scarring due to aphthae

REFERENCES 1. Kozlak ST, Walsh SJ, Lalla RV. Reduced dietary intake of vitamin B12 and folate in patients with recurrent aphthous stomatitis. J Oral Pathol Med.

2010;39(5):420-423.; 2. Plewa MC, Chatterjee K. Aphthous stomatitis. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK431059/. Updated January 24, 2020. Accessed March 11, 2020.; 3. Barrons RW. Treatment strategies for recurrent oral aphthous ulcers. Am J Health-Syst Pharm. 2001;58(1):41-50.; 4. Preeti L, Magesh KT, Rajkumar K, Karthik R. Recurrent aphthous stomatitis. J Oral Maxillofac Pathol. 2011;15(3):252-256.; 5. Altenburg A, Zouboulis CC. Current concepts in the treatment of recurrent aphthous stomatitis. Skin Therapy Lett. 2008;13(7):1-4. https://www.skintherapyletter.com/aphthous- stomatitis/treatment-concepts/. Published: September 1, 2008.; 6. Volkov I, Rudoy I, Abu-Rabia U, Masalha T, Masalha R. Case report: recurrent aphthous stomatitis responds to vitamin B12 treatment. Can Fam Physician. 2005;51(6):844845.; 7. Carrozzo M. Vitamin B12 for the treatment of recurrent aphthous stomatitis. Evid Based Dent. 2009;10(4):114-115.; 8. Ship JA, Chavez EM, Doerr PA, Henson BS, Sarmadi M. Recurrent aphthous stomatitis. Quintessence Int. 2000;31(2):95-112.; 9. Ankar A, Kumar A. Vitamin B12 deficiency (cobalamin). StatPearls [Internet]. https://www. ncbi.nlm.nih.gov/books/NBK441923/. Updated: January 11, 2019. Accessed: March 12, 2020. 36

NOVEMBER 2020 [Vol.7 No.9]

100 mcg / 50 mcg

250 mcg / 50 mcg

500 mcg / 50 mcg

Bioequivalent alternative to ADVAIR® DISKUS® for appropriate patients with asthma or COPD

Wixela Inhub

100 mcg / 50 mcg

Wixela Inhub

250 mcg / 50 mcg

Wixela Inhub

500 mcg / 50 mcg

(fluticasone propionate and salmeterol inhalation powder, USP)

Large dose counter window

(fluticasone propionate and salmeterol inhalation powder, USP)

Device lockout after final dose

(fluticasone propionate and salmeterol inhalation powder, USP)

Similar steps as ADVAIR DISKUS

View the instructional How-To-Use video at WIXELA.CA Wixela Inhub (fluticasone propionate/salmeterol) is a combination of an inhaled corticosteroid (ICS) and a long-acting beta2-adrenergic agonist (LABA) indicated for the maintenance treatment of asthma, in patients with reversible obstructive airways disease. Wixela Inhub should be prescribed for patients not adequately controlled on a long-term asthma control medication, such as an ICS, or whose disease severity clearly warrants treatment with both an ICS and a LABA. Wixela Inhub 250 mcg/50 mcg and Wixela Inhub 500 mcg/50 mcg are indicated for the maintenance treatment of COPD, including emphysema and chronic bronchitis, in patients where the use of a combination product is considered appropriate. Consult the Product Monograph at https://health-products.canada.ca/dpd-bdpp/index- eng.jsp for more information about: • Contraindications regarding IgE mediated allergic reactions to lactose or milk, patients with cardiac tachyarrhythmias, patients with untreated fungal, bacterial or tuberculous infections of the respiratory tract and in the primary treatment of status asthmaticus or other acute episodes of asthma • Other relevant warnings and precautions regarding serious asthma-related events (hospitalizations, intubations, death), treating acute symptoms of asthma or COPD, excessive use and use with other LABA products, abrupt stop of treatment, caution in patients with cardiovascular disorders, central nervous system effects, symptoms of laryngeal spasm, irritation, or swelling, caution in patients who are transferred from systemically active corticosteroids to inhaled corticosteroids, systemic endocrine effects, reversible metabolic changes, eosinophilic conditions, enhanced effect of corticosteroids on patients with cirrhosis, immediate hypersensitivity reactions, candidiasis, masking some signs of infection and new infections, serious course of chickenpox and measles, glaucoma, cataracts, central serous chorioretinopathy, paradoxical bronchospasm, pneumonia (COPD Patients) and active monitoring during long term therapy • Conditions of clinical use, adverse reactions, drug interactions and dosing instructions The Product Monograph is also available by calling 1-844-596-9526. WIXELA and INHUB are registered trademarks of Mylan Pharmaceuticals ULC. ADVAIR and DISKUS are registered trademarks of Glaxo Group Limited. The Mylan logo is a registered trademark of Mylan Inc. License use by Mylan Pharmaceuticals ULC. © 2020 Mylan Pharmaceuticals ULC. All rights reserved. WIX-2020-0075B - JN2020

MICHAEL DO MedEssist Toronto, ON


NOVEMBER 2020 [Vol.7 No.9]


Empowering pharmacists,


MICHAEL DO has created technology that gives pharmacists the time to perform at the top of their patient care game and makes it easier for patients to take their medications properly.

[Vol.7 No.9] NOVEMBER 2020



oronto-based pharmacist Michael Do is passionate about empowering patients (and their pharmacists) with technology. So much so, he’s been working 60 hours a week for the last three months to fine-tune the healthcare apps he and his team at MedEssist have been developing— all while still managing a busy downtown Toronto pharmacy himself. Do founded his healthcare technology company, MedEssist, in November 2018 after spending eight years as a community pharmacist. Drawing on his experience in the community, he saw gaps in medication management and adherence among patients that he felt technology solutions could remedy. He also wanted to give pharmacists a way to manage their workloads more efficiently, while being able to grow their businesses and improve their overall image as doing more than “counting pills.” His instincts around the need for technology solutions was bang on. In a short time, MedEssist apps are already being endorsed by pharmacy associations across the country and in use by thousands of pharmacies and patients. And Do says there are many more technology solutions he wants to bring to fruition in the coming years.

Tell us more about what these apps do?

MedEssist Lead Developer Bashir Egeh gave up his job as a community pharmacist and moved provinces to code full-time. “Pharmacists have a lot to do— especially now. I’m hoping what we’re developing will make their lives easier so they can focus on patients.”


When we first launched, our mobile app was a tool to help patients with their medications. Prior, we were seeing patients leave the pharmacy confident about the medication we had explained to them and yet still have issues and missing doses. With the app, patients see a picture of what the pills look like, and then get a reminder about how and when to take them. And it’s grown from there. Now we provide a platform to help pharmacies manage patients for their flu shots and COVID-19 tests too. (All the apps are free for patients and pharmacies pay a nominal subscription fee for access to the platform and tools.)

How do you run a new business and still manage a pharmacy? I have full

control over the schedule at the pharmacy and am only there about five hours a week now, so that helps. I also like that I have been able to use our apps at this store for ‘real-world’ testing. On the MedEssist side, I also have a great team and couldn’t do it without them.

Tell us about your team. I have five

How are you marketing your solutions? Initially we went pharmacy to

Were you always into technology?

You’re often asked to speak to pharmacy students. Tell us more about that. There are two different reasons

full-time employees (two are experienced pharmacists), as well as part-time staff and pharmacy students. Pharmacist Bashir Egeh is the lead developer and I like putting a spotlight on him because not a lot of pharmacists code to the level that he does. He does the heavy lifting and I do content design and lighter coding. But in a true sign of the times, I have yet to meet him in person because we hired him after the COVID-19 shut-down. I did some coding in high school, but don’t have any official training.

What are some of the challenges you’ve faced?

I’m working a lot and when you start off, everything is hard. But then again, most pharmacists are working really hard during this time. The fact I’m building solutions for 40

them, to make work life easier, inspires me. Pharmacists and patients still don’t know a lot about technology so there is a lot of room to grow in this aspect, too. It’s exciting getting patients and pharmacists more comfortable with using technology.

NOVEMBER 2020 [Vol.7 No.9]

pharmacy, asking pharmacists to try our tools and gain our trust. I don’t think you can just throw an ad online and expect people to trust you. We’ve made a lot of progress in several provinces with the support of pharmacy associations. In Nova Scotia, for example, the association reached out to us because they were looking for solutions and it went from there.

I get invited, either to talk about community pharmacy and how to have a successful student rotation, or to discuss technology in pharmacy. I’ve given talks at both the University of Toronto and University of Waterloo. With any opportunity to talk to students, my goal is always to expand their thinking in some way. I love working with students too. We have student rotations at

both my pharmacy and with MedEssist. I feel like if I can teach them something or motivate them in some way, then I’m having a positive influence on the countless patients that student is going help throughout their career.

How did you know you were successful? By the fact that lots of people

are using our apps without any issues. We had more than 10,000 patients register for the flu shot using our platform even before flu season began. I think that’s pretty incredible.

What do you attribute to your success so far, especially with so many competitors in the market? All of

our solutions are fundamentally unique to pharmacy, and I believe could have only been built by a pharmacist. I think that’s why our pharmacies love working with us. I think another reason for our success is how we’ve been able to build trust both with patients and with other pharmacists. Eventually the trust that we’ve built, by holding ourselves to a higher standard, will be the most valuable asset we will ever own.

What’s next on the agenda?

Once pharmacists try our products, they end up contacting us with ideas of what they want us to make next. It’s a long list. COVID-19 vaccinations are on the horizon. A lot of these vaccines are two-dose, so being able to help pharmacists and patients get those doses while supplies are limited is going to be very important.

What’s your advice to other pharmacists who want to innovate?

“I think another reason for our success is how we’ve been able to build trust both with patients and with other pharmacists. Eventually the trust that we’ve built, by holding ourselves to a higher standard, will be the most valuable asset we will ever own.”

I think working as a pharmacist you pick up so many important soft skills that can be useful with anything you want to do. Skills such as being able to work in a high-paced environment, communicating through all sorts of barriers, problem-solving, being extremely attentive and detailed, or being a lifelong learner. If you are mindful of these things, you can hone these skills within the pharmacy in order to solve all sorts of problems in the healthcare system. The healthcare system is changing, and pharmacies can and should play a bigger role in shaping that change.


This 1-minute video explains the MedEssist app: https://www.youtube.com/ watch?v=dh2HC7f9u8g

Do you have work-life balance at this point? No. When you launch something it’s

a limitless amount of time you can put into it. But I know I can’t sustain this, and after we finish implementing our COVID-19 app, I’ll definitely scale back.

[Vol.7 No.9] NOVEMBER 2020



ARE YOU LISTENING YET? Check out these podcasts by and for pharmacists BY ROSALIND STEFANAC


NOVEMBER 2020 [Vol.7 No.9]


lthough podcasts started catching on back in 2004 with the onset of broadband Internet access, it’s only in the last few years that we’ve seen the genre really explode, especially when it comes to all things healthand pharmacy-related. Best of all, we’re seeing more and more pharmacists and pharmacy organizations producing podcasts, and drawing in audiences of pharmacy veterans and new grads alike. Discussions delve into everything from medication issues, new health trends and pandemics preparedness, to overcoming burnout and finding your passion in the profession again. Here are some pharmacy-inspired podcasts to put on your radar, available via most popular podcast platforms, such as Apple Podcast, Google Podcast, Spotify, iTunes, Podbean and Stitcher. This is by no means an extensive list, so let us know about any great pharmacy podcasts you’re listening to these days that we missed.

Canadian Pharmer


THEME: A year in, community

THEME: Launched by the

pharmacist Michelle Stewart is still FREQUENCY/REACH: offering useful, practical healthcare 13 episodes, 3,553 downloads information in her personal podcast. Every episode, she gathers and TRY THIS EPISODE: Rosacea, Atopic Dermatitis, reviews therapeutic information Peri-oral Dermatitis, and provides tips on real-life uses Allergic Rhinitis in treatment. Stewart’s mission is to help listeners enhance their practice and boost confidence “in the white coat.” All topics are geared towards the interests of pharmacists, pharmacy techs and pharmacy students.

University of Toronto’s Leslie Dan Faculty of Pharmacy, this podcast aims to explore emerging professional trends FREQUENCY/REACH: in pharmacy, as well the latest 5 to 8 episodes per season (next series to be released by March 2021); breakthrough science led by U of T’s research teams. It will also 281 downloads for its most popular shows (1,051 downloads across all highlight success stories from episodes to date). alumni and current student TRY THIS EPISODE: experiences. Season 1 was Ep 5: Continuous Professional Development with Jamie Kellar created and hosted by PharmD students and dives into topics such as interprofessional collaboration and common ailments.

CorConsult Rx.


THEME: Focused on evidence-based

medicine and drug reviews, these FREQUENCY/REACH: US-based pharmacists interview weekly, 146 episodes to date. clinical experts and use patient case studies to explore a melange TRY THIS EPISODE: Testosterone Replacement of health topics, from acne vulgaris Therapy and dyslipidemia to traumatic brain injuries. Listeners can download patient case studies to follow along and get links to the trials and guidelines referenced in each podcast for easy access.

I’m Pharmacy


Med Thread



THEME: Hosted by pharmacists

Cathy Balsom and Mike Chong working out of Memorial University’s School of Pharmacy in Newfoundland and Labrador, this podcast offers an upbeat approach to a mix of health­ care topics. Now in its second season, the hosts tackle subjects like weight loss, vaping and palliative care.

The Happy PharmD


THEME: US-based pharmacists Alex

Barker and Chris Baechle aim to inspire listeners with discussions around what’s stopping pharmacists from being innovative, or what FREQUENCY/REACH: to do when you’re disappointed weekly, 40 episodes to date; 1,500 downloads a month with your business results. Barker, TRY THIS EPISODE: a career coach and founder of the Ep. 8: The Pharmacist’s Happy PharmD company behind the Value podcast, says he aims to inspire other pharmacists “to go against the flow” and create a better life. He had set a goal for the year of helping 500 pharmacists transition to happier jobs by January 2021.

FREQUENCY/REACH: monthly, 400 downloads per episode (on hiatus due to COVID-19 restrictions) TRY THIS EPISODE: Season 2, Ep 11 Fall-al-al-al-al (exploring the correlation between falls and medication)

(continued on page 44)

[Vol.7 No.9] NOVEMBER 2020


Off the Script


THEME: Recent pharmacy grad,

Chris Tse and Advanced Practice Pharmacist Faizan Baig host this podcast aimed at providing a fresh perspective on currents trends in REACH: pharmacy practice and the world weekly, 35 episodes to date; 200 regular listeners of medicine. “Ever since I started pharmacy school, I have been TRY THIS EPISODE: Season 1, Ep. 9: surrounded by a cloud of negativity Preventative Medicine: from practising pharmacists who Changing how we complain about the profession but Approach Healthcare aren’t doing anything to advocate for it,” says Baig. “We wanted to do something different and have had listeners say they really enjoy that we’re positive about the profession.” Episodes cover everything from what it means to be a pharmacist to how to refill medications during a pandemic.

Pharmacists’ Matters


THEME: Launched by the Ontario

Pharmacists Association (OPA), this podcast aims to “address challenges the pharmacy profession is facing and the opportunities, too,” says host FREQUENCY/REACH: and OPA CEO Justin Bates. To date, monthly, 8 episodes to date; approximately 200 listeners topics have ranged from pharmacy and pandemic resources, to LGBTQ+ per episode TRY THIS EPISODE: care in pharmacy and the profession’s Ep. 8 COVID-19 testing in role in addressing racism. The latest pharmacy: the Alberta story episode features political analyst Amanda Galbraith in a discussion about the latest in US and Canadian politics.

Pharmacy in Phlux


THEME: BC-based pharmacy

consultants and industry veterans Derek Desrosiers and Phil Hauser host this podcast launched in March 2020 to stimulate conversations with FREQUENCY/REACH: pharmacy thought-leaders about 11 episodes to date with a goal to reach 17 per year; the profession and the business of 147 views for its most pharmacy. The hosts engage guests to popular topics. discuss topics such as the experience TRY THIS EPISODE: of acquiring a new pharmacy, Ep. 2: How pharmacists are regulating the profession of pharmacy coping with the pandemic and how to cope during COVID-19. The podcast is available in video as well as audio formats, and is part of the Conversations That Matter family of podcasts produced by Oh Boy Productions in Vancouver.

Podcast creators and hosts, Faizan Baig and Chris Tse.

The Pharmacists Are In


THEME: Touted as the “Canadian

pharmacists’ guide to expanding and innovating scope of care within the pharmacy profession.” Hosted by pharmacist/owner, assistant professor and researcher John Papastergiou, discussions have explored the role of pharmacists in managing the opioid crisis, vaccinations and behavioral/psychosocial counselling in pharmacy practice.


Reefer Medness


THEME: In January 2018, community

FREQUENCY/REACH: every 4-6 weeks (delayed with COVID-19) 10 episodes to date; 20,000 listeners per episode. TRY THIS EPISODE: Battling Vaccination Myths and Increasing Customer Loyalty

NOVEMBER 2020 [Vol.7 No.9]

pharmacy veteran Trevor Shewfelt FREQUENCY/REACH: teamed up with Kirk Nygquist, an bi-monthly (60 episodes to date); 100-150 listeners per out-post nurse working with First episode Nation communities, to help educate TRY THIS EPISODE: listeners on all things related to Ep. 34, Sex and Pharmacy cannabis. Those tuning in are mostly (cannabis as a treatment for healthcare providers, plus a few other sexual dysfunction) “cannabis-curious” listeners. “Lots of patients are using cannabis and they may really benefit from a pharmacist’s advice,” says Shewfelt. “I don’t think we’ll ever run out of topics.”


SMART Pharmacist Podcast




American Society of Hospital Pharmacy (ASHP) Podcasts, features interviews with pharmacy leaders and researchers on the latest hot topics in the profession, from a US perspective.

THEME: Produced by the Institute for

Safe Medication Practices Canada, episodes focus on medication safety in community pharmacy and how to incorporate safer medication practices. Topics explored include drug-drug interactions in the elderly population and what happens after a medication incident.

Conscious Pharmacist Podcast is aimed at pharmacists who choose to “practice with purpose.”

FREQUENCY/REACH: bi-monthly, 6 episodes to date

Healthcare Roundtable is hosted by a clinical pharmacist and features discussions with various healthcare professionals for a broader view on current health-related topics.

TRY THIS EPISODE: Ep 4, Compounding Errors

OVERxDose is hosted by a pharmacy student who uses humour to explore the future of pharmacy. Check out two notable min-series in this podcast focusing on mental health and social media.

Talk to Your Pharmacist

Pharmacist Diaries is a weekly podcast that dives deep behind the scenes into the lives of pharmacists from around the world.



Pharmacy in Practice provides a UK perspective on the profession and the latest hot healthcare topics.

THEME: As a US-based clinical

TWIV (This week in Virology) is a weekly podcast, particularly timely now as it focuses on all things virus-related.

pharmacist with a PharmD and MBA, host Hillary Blackburn founded this podcast in 2017 to create a platform for pharmacy leaders doing innovative FREQUENCY/REACH: things in the profession. In addition to 158 episodes to date. sharing their leadership stories, guests TRY THIS EPISODE: also provide perspective on things like Ep. 151 Retail pharmacy: Balancing COVID and Mom taking the leap to entrepreneurship and Life with Dr. Linda Dumas investing in a pharmacy business, to translating your skills to non-traditional pharmacy career paths. There’s even an episode this year with BC-based pharmacist Dr. Arden Barry speaking about pharmacist prescribing.

Your Financial Pharmacist offers insights on debt, investing and a host of other financial topics from a pharmacist’s perspective. And finally, if you want to do some exploring yourself, go to the USbased Pharmacy Podcast Network (https://pharmacypodcast.com) to check out some 20 podcasts with more than 800 episodes geared to the pharmacy profession. Did we miss your favourite podcast? Tell us about it and we’ll add it to the list! Email vwood@ensembleiq.com



1 877 687-7321 ext.:1266

[Vol.7 No.9] NOVEMBER 2020


Back Talk

Creative thoughts and smart ideas for pharmacy owners and managers


WHICH form of automation is the right fit for my practice?

A retail operation that sees patients come consistently for refills of their vial medication may benefit from vial packaging automation, whereas one that supports a LTC facility would benefit from blister card packaging. It’s also important to think ahead. What are your plans for future services/expansion? Your automation systems should be configurable and able to integrate with other technology as your practice changes and grows.

WHEN is the right time for automation at my store?



HOW TO PLAN FOR PHARMACY AUTOMATION Automation is a significant investment that more pharmacies are considering. Here are some important questions to ask before deciding which technology is right for your pharmacy.

WHAT are the needs at your practice?

Automation can be helpful, but it is only as good as its purpose. One of the first considerations before you implement any form of automation is to know what are you trying to accomplish. Efficiency is often the root contributor to successfully implementing automation in pharmacy practice. Pharmacies may be looking to free up labour for relationship building, services and other projects. That kind of investment can reap benefits in terms of patient loyalty: patients who have a personalized relationship with staff are 46

more likely to return and to recommend you to others. A sudden spike in prescription volumes, disruptions in available labour, or general growth can also spur the need for automation.

HOW will I implement automation?

Take a look at your current prescription count. What is your range of refills vs. new prescriptions? How many of your current patients are on blister cards? It’s important to understand how your staff ’s time is currently being used in your pharmacy. Depending on what you find out, various forms of automation are available to help automate routine processes: from strip-packaging medication to filling vials or packaging blister cards. Automation can even go a step further and support technical checks to ensure the right pill has been packaged.

NOVEMBER 2020 [Vol.7 No.9]

There are factors to consider in timing. A new store has more options for building the floor plan around the machinery, whereas with a store that is currently operating, you need to work with the space you have. However, there are various models of machinery available to work within your workflow. To develop your business case for automation, take into account both your current and forecasted script volumes for the prescriptions to be handled by automation, as well as your current workflow and staffing resources.

WHO is the right partner for me?

The right partner/vendor can help you navigate through these decisions. Look for vendors who help you understand the business case for your specific automation investment. Your labour situation, script count and growth plans are unique to you and cannot be generalized. Look for a partner who truly understands your pharmacy’s workflow. Identifying a business case is the first step, but implementation is also crucial to see a return on your investment. Is your vendor able to support change management in your store? Finally, does your vendor offer support once you are up and running? Staff may change, your needs may change; it’s important to have a partner in this journey who will support you and your practice. Take the time to evaluate, innovate and personalize automation to your practice needs. Pavithra Ravi is a healthcare consultant with a background in retail pharmacy.


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Pharmacy Practice+Business - November 2020  

Pharmacy Practice+Business - November 2020