The medical letter on drugs and therapeutics april 13 2015

Ivermectin Cream (Soolantra) for Rosacea The FDA has approved a 1% cream formulation of the antiparasitic drug ivermectin (Soolantra – Galderma) for topical treatment of inflammatory lesions of rosacea. Ivermectin is available... Advice for Travelers Patients planning to travel to other countries often ask for information about prevention of diarrhea, malaria, and other travel-related conditions. Vaccines recommended for travelers based on... In Brief: Severe Bradycardia with Sofosbuvir and Amiodarone The FDA recently announced changes in the labeling of the hepatitis C drugs Sovaldi (sofosbuvir) and Harvoni (sofosbuvir/ledipasvir) to warn about a risk of serious and potentially...

The Medical Letter ® on Drugs and Therapeutics Objective Drug Reviews Since 1959 Volume 57 ISSUE ISSUE No 1433 1466 Volume 56 April 13, 2015 IN THIS ISSUE Ivermectin Cream (Soolantra) for Rosacea p 51 Advice for Travelers p 52 In Brief: Severe Bradycardia with Sofosbuvir and Amiodarone p 58 Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S 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 U.S 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 Published by The Medical Letter, Inc • A Nonprofit Organization 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 Objective Drug Reviews Since 1959 Volume 57 ISSUE ISSUE No 1433 1466 Volume 56 ▶ April 13, 2015 Take CME Exams ALSO IN THIS ISSUE Advice for Travelers .p 52 In Brief: Severe Bradycardia with Sofosbuvir and Amiodarone p 58 Ivermectin Cream (Soolantra) for Rosacea The FDA has approved a 1% cream formulation of the antiparasitic drug ivermectin (Soolantra – Galderma) for topical treatment of inflammatory lesions of rosacea Ivermectin is available in the US in tablets (Stromectol, and generics) for treatment of onchocerciasis and other worm infestations and as a 0.5% lotion (Sklice) for treatment of head lice Pronunciation Key Ivermectin: eye" ver mek' tin Soolantra: soo lahn' tra MECHANISM OF ACTION — The mechanism of action of ivermectin in rosacea is unknown The drug has antiparasitic activity and possibly an antiinflammatory effect, and Demodex mites have been implicated in the pathogenesis of the inflammatory facial eruptions that characterize the disease.1 Table Pharmacology Drug class Antiparasitic drug Formulation 1% cream in 30, 45, and 60 g tubes Route Topical Tmax 10 hours Half-life (terminal) ~6.5 days Metabolism Primarily by CYP3A4 Excretion Not characterized TREATMENT OF ROSACEA — Rosacea is a common, chronic inflammatory facial eruption of unknown cause characterized by erythema, telangiectasias, and recurrent, progressive crops of acneiform papules and pustules, usually on the central part of the face Topical antibacterial drugs such as metronidazole (Metrocream, and others) and azelaic acid (Finacea) are generally tried first, sometimes in combination with oral antimicrobials, such as low-dose doxycycline, which can produce a more rapid response Topical retinoids are used for patients who not respond to topical antimicrobials The oral retinoid isotretinoin is generally reserved for patients with severe inflammatory nodulocystic disease A topical gel formulation of the alpha2 agonist brimonidine (Mirvaso) appears to be somewhat effective in reducing facial erythema in patients with rosacea, but it has no effect on the papulopustular component of the disease.2 Light and laser therapies can decrease the severity of telangiectasias and erythema CLINICAL STUDIES — FDA approval of ivermectin cream for treatment of rosacea was based on two 12week, randomized, double-blind trials that compared once-daily application of ivermectin cream with its vehicle alone in a total of 1371 patients with moderate to severe papulopustular rosacea In both trials, complete or almost complete clearing of lesions occurred in significantly more patients treated with ivermectin (38.4% and 40.1%) than with the vehicle alone (11.6% and 18.8%) Ivermectin reduced the number of inflammatory lesions from baseline by 76% and 75%, compared to reductions of 50% with the vehicle alone in both trials.3 Two 40-week extensions of these trials found that the percentages of patients with complete or almost complete clearing of lesions increased to 71.1% and 76% in the two studies with continued use of ivermectin cream.4 A 16-week randomized trial in 962 patients with moderate to severe papulopustular rosacea found that ivermectin 1% cream once daily was significantly more effective than metronidazole 0.75% cream twice daily in reducing the number of inflammatory lesions from baseline (83.0% vs 73.7%) and in clearing or almost clearing the lesions (84.9% vs 75.4%).5 51 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter Vol 57 (1466) ® ▶ Table Some Topical Drugs for Rosacea Drug Metronidazole – generic Metrocream (Galderma) Metrolotion Metrogel Some Formulations Usual Dosage1 Cost2 Apply once/d 0.75% gel, cream, lotion; 1% gel 0.75% cream $151.80 517.40 0.75% lotion 0.75%, 1% gel 594.70 311.404 Azelaic acid – Finacea (Bayer) 15% gel Apply bid 255.00 Ivermectin – Soolantra (Galderma) 1% cream Apply once/d 275.00 A pea-sized amount should be applied in a thin layer to each affected area of the face Approximate WAC for the smallest size metered-dose pump or tube available WAC = wholesaler acquisition cost, or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent actual transactional prices Source: AnalySource® Monthly March 5, 2015 Reprinted with permission by First Databank, Inc All rights reserved ©2015 www.fdbhealth.com/policies/drug-pricing-policy Cost of a 45-g tube of 0.75% cream Cost of a 55-g metered-dose pump of 1% gel ADVERSE EFFECTS — Burning and irritation of the skin occurred in ≤1% of patients treated with ivermectin cream in clinical trials No systemic effects of the drug were reported Pregnancy – Based on studies with large doses of oral ivermectin in animals, Soolantra has been classified as category C (evidence of toxicity in animals, no adequate studies in women) for use during pregnancy DOSAGE AND ADMINISTRATION — A pea-sized amount of ivermectin cream should be applied in a thin layer to each affected area of the face (forehead, nose, chin, and each cheek) once daily CONCLUSION — Ivermectin 1% cream (Soolantra) appears to be effective for treatment of papulopustular rosacea, with minimal adverse effects ■ M Brown et al Severe Demodex folliculorum-associated oculocutaneous rosacea in a girl successfully treated with ivermectin JAMA Dermatol 2014; 150:61 Brimonidine gel (Mirvaso) for rosacea Med Lett Drugs Ther 2013; 55:82 L Stein Gold et al Efficacy and safety of ivermectin 1% cream in treatment of papulopustular rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies J Drugs Dermatol 2014; 13:316 L Stein Gold et al Long-term safety of ivermectin 1% cream vs azelaic acid 15% gel in treating inflammatory lesions of rosacea: results of two 40-week controlled, investigator-blinded trials J Drugs Dermatol 2014; 13:1380 A Taieb et al Superiority of ivermectin 1% cream over metronidazole 0.75% cream in treating inflammatory lesions of rosacea: a randomized, investigator-blinded trial Br J Dermatol 2014 Sept 16 (epub) 52 April 13, 2015 Advice for Travelers Related article(s) since publication Patients planning to travel to other countries often ask for information about prevention of diarrhea, malaria, and other travel-related conditions Vaccines recommended for travelers based on their destination, length of stay, and planned activities were reviewed in a previous issue.1 TRAVELERS’ DIARRHEA The most common cause of travelers’ diarrhea, usually a self-limited illness lasting several days, is infection with noninvasive strains of Escherichia coli Infections with other types of bacteria such as Campylobacter jejuni, Shigella spp., and Salmonella spp., viruses, and parasites are less common In recent years, norovirus has become a more frequent cause of diarrhea in travelers; according to one study, norovirus infection was detected in 16% of US travelers returning from Mexico with diarrhea.2 Travelers to areas where hygiene is poor should avoid raw vegetables, fruit they have not peeled themselves, unpasteurized dairy products, cooked food not served steaming hot (dry foods such as bread are usually safe), and tap water, including ice TREATMENT — For mild diarrhea without fever or bloody stools, loperamide (Imodium, and others), an over-the-counter synthetic opioid (4-mg loading dose, then mg orally after each loose stool to a maximum of mg/d for adults), often relieves symptoms in 45 kg: tab once/wk 30 mg base once/d 0.5 mg/kg base once/d Alternative: Primaquine phosphate13,14 10 11 12 13 14 Start: 1-2d before travel Stop: wks after leaving malarious zone Start: ≥2 wks before travel12 Stop: wks after leaving malarious zone Start: 1-2d before travel Stop: wk after leaving malarious zone No drug guarantees protection against malaria Travelers should be advised to seek medical attention if fever develops during travel or after they return Insect repellents, insecticide-impregnated bed nets, and proper clothing are important adjuncts for malaria prophylaxis Chloroquine-resistant P falciparum occurs in all malarious areas except Central America (resistance occurs in Panama east of the Canal Zone), Mexico, Haiti, the Dominican Republic, Paraguay, North and South Korea, most of rural China, and some countries in the Middle East (chloroquine resistance has been reported in Yemen, Saudi Arabia, and Iran) P vivax with decreased susceptibility to chloroquine is a significant problem in Papua New Guinea and Indonesia There are also reports of resistance from Burma (Myanmar), Vietnam, the Solomon Islands, Vanuatu, Turkey, Guyana, Brazil, Colombia, and Peru (JK Baird, Clin Microbiol Rev 2009; 22:508) Chloroquine-resistant P malariae has been reported from Sumatra, Indonesia (JD Maguire et al, Lancet 2002; 360:58) Primaquine is given for prevention of relapse after infection with P vivax or P ovale In addition to primary prophylaxis, some experts also prescribe primaquine phosphate 30 mg base/d (0.5 mg/kg base/d for children) for 14 days after departure from areas where these species are endemic (Presumptive Anti-Relapse Therapy [PART], “terminal prophylaxis”) Since this is not always effective as prophylaxis, others prefer to rely on surveillance to detect cases when they occur, particularly when exposure was limited or doubtful See also footnote 12 Alternatives for patients who are unable to take chloroquine include atovaquone/proguanil, mefloquine, doxycycline, or primaquine dosed as for chloroquineresistant areas Chloroquine should be taken with food to decrease gastrointestinal adverse effects If chloroquine phosphate is not available, hydroxychloroquine sulfate is as effective; 400 mg of hydroxychloroquine sulfate is equivalent to 500 mg of chloroquine phosphate Atovaquone/proguanil is available as a fixed-dose combination tablet: adult tablets (Malarone, and others; 250 mg atovaquone/100 mg proguanil) and pediatric tablets (Malarone Pediatric, and others; 62.5 mg atovaquone/25 mg proguanil) To enhance absorption and reduce nausea and vomiting, it should be taken with food or a milky drink The drug should not be given to patients with severe renal impairment (creatinine clearance