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Mrx CLINICAL ALERT MRx JULY 2019 CLINICAL ALERT YOUR MONTHLY SOURCE FOR DRUG INFORMATION HIGHLIGHTS CANAGLIFLOZIN AND similar rates of amputation and fracture RENAL OUTCOMES with canagliflozin and placebo. The CREDENCE trial was stopped due to EDITORIAL clear evidence of early renal benefit The Canagliflozin and Renal Events in according to prespecified criteria. STAFF Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial The American Diabetes Association was designed to assess the effects of (ADA) updated their “living” Standards the sodium-glucose cotransporter-2 EDITOR IN CHIEF of Medical Care in Diabetes to include (SGLT2) inhibitor canagliflozin on Maryam Tabatabai findings from the CREDENCE trial. The renal outcomes in patients with PharmD ADA recommends the SGLT2 inhibitors type 2 diabetes mellitus (T2DM) and canagliflozin, dapagliflozin, and albuminuric chronic kidney disease EXECUTIVE EDITOR empagliflozin in patients with T2DM (CKD). CKD was defined as an estimated Carole Kerzic and established CKD based on the glomerular filtration rate (eGFR), 30 RPh drugs’ proven renal benefit. to < 90 mL/min/1.73 m2 with albumin (mg) to creatinine (g) ratio > 300 to DEPUTY EDITORS 5,000. All patients were on stable DIABETES GUIDELINES FOR Jill Bot doses of an angiotensin-converting ELDERLY PATIENTS PharmD, MBA enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). The double- In their clinical practice guidelines Stephanie Christofferson blind study randomized 4,401 patients for treatment of diabetes in older PharmD 1:1 to canagliflozin 100 mg once daily adults, the Endocrinology Society (ES) or placebo. The mean age was 63 provides recommendations regarding Jessica Czechowski years, mean HbA1c was 8.3%, and diabetic screening, assessment, and PharmD mean eGFR was 56.2 mL/min/1.73 m2. treatment as well as management of After a 2.62 year median follow-up, the diabetic complications (e.g., retinopathy, Lara Frick primary outcome, a composite of end- neuropathy, renal disease) and comorbid PharmD, BCPS, BCPP stage renal disease (ESRD), doubling of conditions (e.g., hyperlipidemia, serum creatinine level from baseline hypertension, CVD) in patients ≥ 65 years Leslie Pittman over at least 30 days, or death from of age. For ambulatory patients, lifestyle PharmD renal or cardiovascular (CV) disease modification is the initial approach to was 30% lower with canagliflozin hyperglycemia management. Overall, compared to placebo (43.2 versus 61.2 outpatient pharmacologic treatment per 1,000 patient-years, respectively; regimens should be designed to 95% confidence interval [CI], 0.59 to minimize hypoglycemia; therefore, 0.82; p=0.00001). The results were avoid use of sulfonylureas and glinides consistent across all renal endpoint and prescribe insulin with caution. For components. Secondary CV composite patients who are prescribed insulin, outcomes were also significantly lower frequent and/or continuous glucose with canagliflozin and consistent with monitoring is recommended. the prior Canagliflozin Cardiovascular Assessment Study (CANVAS) program. Other key recommendations include Download at: Unlike CANVAS, CREDENCE reported periodic assessment of cognitive magellanrx.com | MAY 2019 function. If cognitive impairment is detected, a simplified (MSM), persons at risk through heterosexual contact, and medication regimen and glycemic target tailored to persons who inject drugs. Behaviors that increase risk improve compliance and prevent complications are include sexual relationships with a partner living with recommended. For management of comorbid conditions, HIV, inconsistent use of condoms, and shared use of an ACEI or ARB is recommended as initial treatment to drug injection equipment, as well as diagnosis of select maintain target blood pressure of 140/90 mm Hg. In sexually transmitted infections within the previous 6 elderly diabetic patients with congestive heart failure, months. Populations at particular risk include people glinides, thiazolidinediones, and dipeptidyl peptidase-4 who engage in transactional or trafficked sex, men who inhibitors should be used with caution to prevent have sex with men and women, and sexually active worsening of heart failure. transgender women and men; these individuals should be assessed for PrEP using the USPSTF-outlined criteria. PCSK9 INHIBITOR VALUE Currently, the fixed-dose combination of emtricitabine The National Lipid Association (NLA) published a statement and tenofovir disoproxil fumarate (Truvada®), given as on the enhanced value of the proprotein convertase 1 tablet orally once daily, is the only medication FDA- subtilisin/kexin type 9 (PCSK9) inhibitors alirocumab approved for PrEP. (Praluent®) and evolocumab (Repatha®), based on CV outcomes data as well as reductions in list prices (by about 60% to $5,850/year). Since risk reduction is directly proportional BEHAVIORAL HEALTH CORNER to absolute low-density lipoprotein cholesterol (LDL-C), patients with higher starting atherosclerotic CV disease ANTIDEPRESSANT ADVERSE EFFECTS IN (ASCVD) risk and higher LDL-C levels generally achieved greater reduction in major vascular events when treated ELDERLY PATIENTS with anti-hyperlipidemic pharmacotherapy. Based, at least In the US, approximately 15% to 20% of people in part, on ASCVD risk phenotype and LDL-C thresholds, ≥ 65 years of age experience major depressive the NLA determined that PSCK9 inhibitors will provide disorder (MDD). In 2019, the American Geriatrics reasonable value (< $100,000 per quality adjusted life Society (AGS) updated their Beers Criteria® to year [QALY]) in the following 3 groups of patients on advise cautious use or avoidance of selective maximally tolerated statin therapy: extremely high-risk serotonin reuptake inhibitors (SSRIs), serotonin (≥ 40% 10-year ASCVD risk) patients with LDL-C ≥ 70 mg/dL, norepinephrine reuptake inhibitors (SNRIs), and including patients with extensive or active ASCVD burden tricyclic antidepressants (TCAs) in elderly patients. and those with less extensive ASCVD plus extremely high-risk cardiometabolic risk factors; very high-risk A recent systematic review and meta-analysis (≥ 30% to 39% 10-year ASCVD risk) patients with LDL-C (Sobiera DM, et al.) evaluated the adverse effects ≥ 100 mg/dL; and high-risk (< 30% 10-year ASCVD risk) of antidepressants in elderly patients and patients with LDL-C ≥ 130 mg/dL, including patients with included 19 randomized controlled trials and 2 heterozygous familial hypercholesterolemia (HeFH) or observational studies. Most trials were conducted severe hypercholesterolemia ≥ 220 mg/dL. It is generally during the acute treatment phase (≤ 12 weeks). advised to add ezetimibe to statin therapy before adding Antidepressants included SSRIs, SNRIs, TCAs, a PCSK9 inhibitor; however, the NLA states that adding a bupropion, mirtazapine, trazodone, vilazodone, PCSK9 inhibitor directly to a statin may be more efficacious and vortioxetine. Study investigators found that for select patients at very high and extremely high while SNRIs were associated with an increased ASCVD risk, particularly if their LDL-C is at a lower level. incidence of adverse events compared to placebo (high strength of evidence [SOE]), SSRIs showed a PRE-EXPOSURE HIV PROPHYLAXIS similar frequency compared to placebo (moderate SOE). Falls were reported more often with duloxetine In 2017, over 38,000 new cases of human immunodeficiency than placebo (moderate SOE). Limited data prevented virus (HIV) infection were diagnosed in the United States differentiation of adverse events for bupropion, (US). The US Preventive Services Task Force (USPSTF) mirtazapine, trazadone, or vortioxetine. Since the issued guidelines recommending that pre-exposure studies were not designed to evaluate adverse prophylaxis (PrEP) with effective antiretroviral therapy events and there were few head-to-head comparisons be offered to individuals at high risk of acquiring HIV among the antidepressants, no conclusions infection (Grade A recommendation). Persons at risk could be drawn comparing agents within a class. of HIV infection include men who have sex with men 2 | JULY 2019 DRUG INFORMATION HIGHLIGHTS • Update on consumer-level recalls of generic • Jazz Pharmaceuticals’ oral dual-acting dopamine and antihypertension medications due to potential human norepinephrine reuptake inhibitor solriamfetol (Sunosi™) carcinogenic impurities: Teva expanded its voluntary was also designated Schedule IV Controlled Substance recall to include an additional 6 lots of bulk losartan classification. The agent was FDA approved in March potassium USP tablets (50 mg and 100 mg). In addition, 2019 for excessive daytime sleepiness associated with Macleods Pharmaceuticals initiated a voluntary recall narcolepsy or obstructive sleep apnea. Product launch of 32 lots of losartan potassium USP tablets 50 mg is planned in early July 2019. strength and losartan potassium/hydrochlorothiazide • The FDA approved a new 100 mg/mL formation for tablets (various strengths). Both recalls are based on mepolizumab (Nucala®), indicated for eosinophilic detection of N-nitroso-N-methyl-4-amino butyric acid asthma and eosinophilic granulomatosis with polyangiitis, (NMBA) derived from active pharmaceutical ingredient to allow for subcutaneous (SC) administration by the (API) from Hetero Labs. patient or caregiver via a single-dose prefilled auto- • Approved in March 2019, Sage Therapeutics’ brexanolone injector or syringe. Previously, Nucala was only approved (Zulresso™) was recently assigned Schedule IV as
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