The medical letter on drugs and therapeutics february 17 2014

Dapagliflozin (Farxiga) for Type 2 Diabetes Dapagliflozin (dap" a gli fl oe'' zin; Farxiga – Bristol-Myers Squibb/AstraZeneca), an SGLT2 (sodium-glucose co-transporter 2) inhibitor, has been approved by the FDA for oral treatment... Macitentan (Opsumit) for Pulmonary Arterial Hypertension The FDA has approved macitentan (ma" si ten'' tan; Opsumit – Actelion), for oral treatment of pulmonary arterial hypertension (PAH). Macitentan is the second nonselective endothelin...

The Medical Letter ® On Drugs and Therapeutics Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Dapagliflozin (Farxiga) for Type Diabetes .p 13 Macitentan (Opsumit) for Pulmonary Arterial Hypertension p 15 Important Copyright Message The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS Revised 2/28/14: See p 14 The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 The Medical Letter ® On Drugs and Therapeutics Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 56 (Issue 1436) February 17, 2014 www.medicalletter.org Take CME Exams ALSO IN THIS ISSUE Table Pharmacology Macitentan (Opsumit) for Pulmonary Arterial Hypertension p 15 Class Sodium-glucose co-transporter (SGLT2) inhibitor Formulation 5-, 10-mg tablets Dapagliflozin (Farxiga) for Type Diabetes Dapagliflozin (dap” a gli floe’ zin; Farxiga – Bristol-Myers Squibb/AstraZeneca), an SGLT2 (sodium-glucose cotransporter 2) inhibitor, has been approved by the FDA for oral treatment of type diabetes Dapagliflozin is the second SGLT2 inhibitor to be approved for this indication; canagliflozin (Invokana) was the first.1 Table SGLT2 Inhibitors Drug Cost1 Dosage Canagliflozin – Invokana 100-300 mg once/d Dapagliflozin – Farxiga 5-10 mg once/d3 $289.10 289.20 Approximate wholesale acquisition cost (WAC) for 30 days’ treatment Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) February 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Taken before the first meal of the day Maximum dose is 100 mg in patients who have an eGFR of 45 to 59 mL/min/1.73 m2 Should not be used in patients with an eGFR 1500 mg) + Dapagliflozin 10 mg + Placebo -0.5 0.0 Add-on Therapy 24 weeks10 (n=808) Insulin11 + Dapagliflozin + Placebo mg 10 mg -0.89 -0.96 -0.39 † Some patients were taking 30 units/day with 0-2 oral antidiabetic agents Increases from baseline in LDL cholesterol were reported in patients taking dapagliflozin 10 mg (2.9% vs -1.0% with placebo) Hyperphosphatemia, increased serum creatinine, decreased estimated glomerular filtration rate (eGFR), and renal failure have also occurred Use of dapagliflozin in patients with moderate renal impairment (eGFR 30 to 8x ULN was 2.1% with macitentan 10 mg and 0.4% with placebo A decrease in sperm count has occurred with other endothelin receptor antagonists and may also occur in men taking macitentan PREGNANCY — Macitentan is teratogenic in animals It is contraindicated for use during pregnancy (category X) and is available for women only through a restricted access program Pregnancy should be excluded before starting treatment and prevented during treatment and for one month afterwards DRUG INTERACTIONS — Strong CYP3A4 inducers such as rifampin can lower serum concentrations of macitentan, and strong CYP3A4 inhibitors such as ketoconazole and ritonavir can increase them Concomitant use of macitentan with strong CYP3A4 inducers and inhibitors should be avoided.7 DOSAGE, ADMINISTRATION, AND COST — The recommended dosage of macitentan is 10 mg once daily Aminotransferases should be monitored before starting macitentan and as needed during treatment The drug should be discontinued for clinically significant aminotransferase elevations or when elevations are accompanied by an increase in bilirubin >2x ULN or by symptoms of hepatotoxicity Patients with pulmonary veno-occlusive disease should not take macitentan The cost of month’s treatment with macitentan is $6840.8 CONCLUSION — Macitentan (Opsumit) can decrease morbidity in patients with pulmonary arterial hypertension, but the claim that it has been shown to decrease mortality is misleading □ 16 Tadalafil (Adcirca) for pulmonary arterial hypertension Med Lett Drugs Ther 2009; 51:87 Ambrisentan (Letairis) for pulmonary arterial hypertension Med Lett Drugs Ther 2007; 49:87 Y Wu et al An update on medical therapy for pulmonary arterial hypertension Curr Hypertens Rep 2013; 15:614 W Diller Opsumit label and pricing suggest Actelion’s gamble ready to pay off The Pink Sheet October 28, 2013 MH Bolli et al The discovery of N-[5-(4-bromophenyl)-6-[2-[(5bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N’-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist J Med Chem 2012; 55:7849 T Pulido et al Macitentan and morbidity and mortality in pulmonary arterial hypertension N Engl J Med 2013; 369:809 Inhibitors and inducers of CYP enzymes and P-glycoprotein Med Lett Drugs Ther 2013; 55:e44 Approximate wholesale acquisition cost (WAC) Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) February 5, 2014 Reprinted with permission by FDB, Inc All rights reserved ©2014 www.fdbhealth.com/policies/drug-pricing-policy Actual retail price may be higher Coming Soon in The Medical Letter: Afatinib (Gilotrif) for Lung Cancer Riociguat (Adempas) for PAH Tobramycin Inhalation (Bethkis) for Cystic Fibrosis Coming Soon in Treatment Guidelines: Drugs for Diabetes Drugs for Hypertension The Medical Letter ® On Drugs and Therapeutics EDITOR IN CHIEF: Mark Abramowicz, M.D EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School EDITOR: Jean-Marie Pflomm, Pharm.D ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine Jane P Gagliardi, M.D., M.H.S., F.A.C.P Duke University School of Medicine Jules Hirsch, M.D., Rockefeller University David N Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre Richard B Kim, M.D., University of Western Ontario Hans Meinertz, M.D., University Hospital, Copenhagen Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine Dan M Roden, M.D., Vanderbilt University School of Medicine Esperance A.K Schaefer, M.D., M.P.H., Harvard Medical School F Estelle R Simons, M.D., University of Manitoba Neal H Steigbigel, M.D., New York University School of Medicine Arthur M F Yee, M.D., Ph.D., F.A.C.R., Weill Medical College of Cornell University SENIOR ASSOCIATE EDITOR: Amy Faucard MANAGING EDITOR: Susie Wong ASSISTANT MANAGING EDITOR: Liz Donohue PRODUCTION COORDINATOR: Cheryl Brown EXECUTIVE DIRECTOR OF SALES: Gene Carbona FULFILLMENT & SYSTEMS MANAGER: Cristine Romatowski DIRECTOR OF MARKETING COMMUNICATIONS: Joanne F Valentino VICE PRESIDENT AND PUBLISHER: Yosef Wissner-Levy Founded in 1959 by Arthur Kallet and Harold Aaron, M.D Copyright and Disclaimer: The Medical Letter is an independent nonprofit organization that provides health care professionals with unbiased drug prescribing recommendations The editorial process used for its publications relies on a review of published and unpublished literature, with an emphasis on controlled clinical trials, and on the opinions of its 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inquiries to: info@medicalletter.org or call 800-211-2769 x315 Special fees for bulk subscriptions Special classroom rates are available Back issues are $12 each Major credit cards accepted Copyright 2014 ISSN 1523-2859 The Medical Letter • Volume 56 • Issue 1436 • February 17, 2014 The Medical Letter ® Online Continuing Medical Education To take CME exams and earn credit, go to: medicalletter.org/CMEstatus Issue 1436 Questions (Correspond to questions #19-24 in Comprehensive Exam #70, available July 2014) Dapagliflozin (Farxiga) for Type Diabetes Dapagliflozin decreases renal glucose reabsorption and increases: a insulin production b insulin sensitivity c urinary glucose excretion d glucagon synthesis Adverse effects of dapagliflozin include: a urinary tract infection b weight gain c severe hypoglycemia d all of the above A 56-year-old man with recent onset of type diabetes has not responded adequately to metformin monotherapy and asks you to prescribe Farxiga You could tell him that: a there are no studies showing that it actually lowers HbA1c b comparative studies have shown that other drugs are more effective when added to metformin c it has caused severe injection reactions d its long-term safety is unknown Macitentan (Opsumit) for Pulmonary Arterial Hypertension In the clinical trial comparing macitentan to placebo, the active drug: a reduced morbidity b lowered the incidence of clinical worsening of PAH c increased the 6-minute walking distance d all of the above Adverse effects of macitentan have included: a anaphylaxis b anemia c reversible posterior leukoencephalopathy d none of the above Use of macitentan during pregnancy: a has been found to be safe b is contraindicated c should be discontinued after the first trimester d may be reasonable if the benefit is thought to outweigh the risk ACPE UPN: Per Issue Exam: 0379-0000-14-436-H01-P; Release: February 17, 2014, Expire: February 17, 2015 Comprehensive Exam 70: 0379-0000-14-070-H01-P; Release: July 2014, 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Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org ... 2014 ISSN 1523-2859 The Medical Letter • Volume 56 • Issue 1436 • February 17, 2014 The Medical Letter ® Online Continuing Medical Education To take CME exams and earn credit, go to: medicalletter.org/CMEstatus... on controlled clinical trials, and on the opinions of its consultants The Medical Letter is supported solely by subscription fees and accepts no advertising, grants, or donations No part of the. .. information call: 800-211-2769 The Medical Letter ® On Drugs and Therapeutics Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume