The medical letter on drugs and therapeutics may 12 2014

Avanafil (Stendra) - Another PDE5 Inhibitor for Erectile Dysfunction The FDA has approved avanafil (Stendra – Vivus), an oral phosphodiesterase type-5 (PDE5) inhibitor, for treatment of erectile dysfunction. It is the fifth PDE5 inhibitor to be approved... Drugs for MRSA Skin and Soft-Tissue Infections Methicillin-resistant Staphylococcus aureus (MRSA), which was traditionally a nosocomially-acquired organism but now frequently occurs in the absence of healthcare exposure, is the...

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) Avanafil (Stendra) — Another PDE5 Inhibitor for Erectile Dysfunction p 37 Drugs for MRSA Skin and Soft-Tissue Infections p 39 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 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 1442) May 12, 2014 www.medicalletter.org Take CME Exams ALSO IN THIS ISSUE Table Pharmacology Drugs for MRSA Skin and Soft-Tissue Infections .p 39 Drug class Route Formulation Tmax Avanafil (Stendra) — Another PDE5 Inhibitor for Erectile Dysfunction Metabolism The FDA has approved avanafil (Stendra – Vivus), an oral phosphodiesterase type-5 (PDE5) inhibitor, for treatment of erectile dysfunction It is the fifth PDE5 inhibitor to be approved for this indication.1 Advertisements on Stendra’s website imply that it has a faster onset of action than other PDE5 inhibitors PDE5 INHIBITORS — There is no convincing evidence that any one PDE5 inhibitor is safer or more effective than any other Their efficacy varies with the etiology of the erectile dysfunction, but in placebo-controlled trials in men with various etiologies, they generally have had an efficacy rate of 60-70%.2 The PDE5 inhibitors all have similar onsets of action, but tadalafil has a much longer duration of action than the other three.1 Elimination Half-life Phosphodiesterase type-5 (PDE5) inhibitor Oral 50, 100, 200 mg tablets 30-45 minutes (delayed 1.12-1.25 hours with a high-fat meal) Hepatic, mainly by CYP3A4 and to a lesser extent by CYP2C Feces (~62%); urine (~21%) ~5 hours MECHANISM OF ACTION — Avanafil is a selective inhibitor of PDE5 Inhibition of PDE5 causes an increase in cGMP levels in the corpus cavernosum, which leads to smooth muscle relaxation and inflow of blood CLINICAL STUDIES — A randomized, doubleblind trial in 646 men with mild to severe erectile dysfunction of various etiologies found that over a 12-week period the percentages of successful attempts at sexual intercourse were higher in men taking avanafil (41% with avanafil 50 mg and 57% with avanafil 100 mg and 200 mg) than in those taking placebo (27%) In a post-hoc analysis of 300 sexual attempts made within 15 minutes of dosing, 64-71% of attempts with avanafil were Table PDE5 Inhibitors for Erectile Dysfunction Drug Avanafil – Stendra (Vivus) Maximum Daily Dose Formulations Usual Dosage 50, 100, 200 mg tabs 100 mg 30 minutes before sexual activity2 2,4 Cost1 200 mg $24.20 Sildenafil – Viagra (Pfizer) 25, 50, 100 mg tabs 50 mg hour before sexual activity 100 mg 28.40 Tadalafil5 – Cialis (Lilly) 2.5, 5, 10, 20 mg tabs PRN use: 10 mg at least 30 minutes before sexual activity Daily use: 2.5 mg once daily 20 mg 31.70 mg 5.40 Vardenafil – Levitra6 (Bayer/GSK) Staxyn6 (Bayer/GSK) 2.5, 5, 10, 20 mg tabs 10 mg hour before sexual activity2,7 20 mg 27.80 10 mg orally disintegrating tabs 10 mg hour before sexual activity 10 mg 17.30 Approximate wholesale acquisition cost (WAC) of a single tablet at the usual dose Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) May 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 Administration with a high-fat meal may reduce the rate and/or extent of absorption Also available as Revatio and generically in 20-mg tablets for treatment of pulmonary arterial hypertension Can be taken from 30 minutes to hours before sexual activity For patients >65 yrs old, the initial dose is 25 mg Also available as Adcirca in 20-mg tablets for treatment of pulmonary arterial hypertension Staxyn and Levitra are not interchangeable Staxyn provides higher systemic exposure than a 10-mg tablet of Levitra For patients >65 years old, the initial dose is mg FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS 37 Table PDE5 Inhibitors in Special Populations Avanafil (Stendra) Hepatic impairment, severe Renal impairment, severe or HD With an alpha blocker1 With a strong CYP3A4 inhibitor2 With a moderate CYP3A4 inhibitor2 Use not recommended Use not recommended Initial dose 50 mg Use not recommended Max 50 mg/d Sildenafil (Viagra) Hepatic impairment Renal impairment, CrCl