The Medical Letter ® on Drugs and Therapeutics Volume 58 ISSUE ISSUE No 1433 1487 Volume 56 February 1, 2016 IN THIS ISSUE Drugs for Acne p 13 Drugs for Rosacea p 16 Rolapitant (Varubi) for Prevention of Delayed Chemotherapy-Induced Nausea and Vomiting p 17 Addendum: Timing of Levothyroxine p 18 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 Volume 58 ISSUE ISSUE No 1433 1487 Volume 56 ▶ February 1, 2016 ALSO IN THIS ISSUE Drugs for Rosacea p 16 Rolapitant (Varubi) for Prevention of Delayed Chemotherapy-Induced Nausea and Vomiting p 17 Addendum: Timing of Levothyroxine p 18 Drugs for Acne Note: An addendum to this article has been published Related article(s) since publication The pathogenesis of acne is multifactorial: follicular hyperkeratinization, bacteria, sebum production, androgens, and inflammation all play a role The grampositive microaerophilic bacteria Propionibacterium acnes promotes development of acne lesions by secreting chemotactic factors that attract leukocytes to the follicle, causing inflammation TOPICAL THERAPY — Salicylic Acid – Widely available over the counter (OTC), topical salicylic acid is a welltolerated keratolytic agent that can be used alone or in combination with other drugs such as benzoyl peroxide Benzoyl Peroxide – The oxidizing agent benzoyl peroxide is available in a wide variety of OTC and prescription preparations for treatment of mild to moderate acne Its effect is primarily due to its antibacterial activity against P acnes Benzoyl peroxide is often used in combination with topical or oral antibiotics It can also be used with a retinoid Benzoyl peroxide can cause skin irritation and bleaching of skin and fabric Contact dermatitis can also occur Unlike other topical antimicrobials, benzoyl peroxide has not been shown to promote bacterial resistance Antibiotics – Topical clindamycin and erythromycin are also commonly used to treat mild to moderate acne Both have antibacterial and anti-inflammatory properties Products containing sulfur and/or sulfacetamide are sometimes used as well, but clinical data supporting their efficacy are limited Topical antibiotics are generally safe and well tolerated Skin irritation can occur, but is typically milder than with retinoids Bacterial resistance can develop, especially to erythromycin; concurrent use of topical antibiotics and benzoyl peroxide protects against development of resistance The combination may also be effective against resistant P acnes Dapsone, an antimicrobial drug used orally to treat leprosy, Pneumocystis pneumonia, and toxoplasmosis, is available in a 5% gel formulation (Aczone) that is effective for treatment of both inflammed and noninflammed Recommendations for Treatment of Acne ▶ Topical salicylic acid and benzoyl peroxide, both available OTC, are often used for initial treatment of acne ▶ A topical antibiotic, often in combination with benzoyl peroxide, is commonly used to treat mild to moderate acne ▶ Many dermatologists now prescribe a topical retinoid for first-line treatment of acne ▶ Retinoid/antimicrobial combinations are more effective than either component alone, particularly for patients with inflammatory lesions ▶ Oral antibiotics are generally prescribed for moderate to severe acne unresponsive to topical drugs ▶ The most effective drug available for treatment of inflammatory acne is isotretinoin; it can clear severe recalcitrant nodular acne, but it has many adverse effects acne lesions Concurrent application of dapsone and benzoyl peroxide can cause temporary yellow or orange discoloration of the skin and facial hair Azelaic Acid – An anti-keratinizing agent with antibacterial and anti-inflammatory activity, azelaic acid (Azelex for acne; Finacea for rosacea) is less irritating than benzoyl peroxide Hypopigmentation can occur, particularly in people with dark skin Retinoids – Topical retinoids such as tretinoin, adapalene, and tazarotene can be used alone or in combination with antibiotics to treat both inflamed and noninflamed acne lesions, or for maintenance treatment Many dermatologists now use them for first-line treatment of acne All topical retinoids normalize keratinization and appear to have anti-inflammatory effects Whether any one of these agents is more effective than any other is not clear Retinoid/antimicrobial combinations are more effective than either component alone, particularly for patients with inflammatory lesions (papules and pustules) Concurrent application of tretinoin and benzoyl peroxide is not recommended because it can cause oxidation of tretinoin and loss of its effectiveness Patients are generally instructed to apply topical retinoids at night because tretinoin is photolabile; adapalene, tazarotene, and the microsphere formu-lation of tretinoin appear to be more stable when exposed to light Adverse effects typically associated with topical retinoids, including dry skin, scaling, photosensitivity, 13 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter ® Vol 58 (1487) February 1, 2016 Table Some Topical Drugs for Acne Drug Antimicrobials Azelaic acid – Azelex (Allergan) Clindamycin – generic Cleocin T (Pfizer) generic Evoclin (Prestium) Clindamycin/benzoyl peroxide – Acanya (Valeant) Onexton (Valeant) generic Benzaclin (Valeant) generic Duac (Stiefel) Some Available Formulations Usual Dosage Cost/Size1 20% cream bid $344.70/30 g 1% gel, soln, lotion, pads bid 1% foam once/d 69.10/30 g 104.90/30 g 277.40/50 g 438.00/50 g 1.2%/2.5% gel 1.2%/3.75% gel 1%/5% gel once/d once/d bid 1.2%/5% gel once/d in the evening 444.00/50 g 444.00/50 g 340.30/25 g 437.40/50 g 162.80/45 g 335.70/45 g Dapsone – Aczone (Allergan) 5% gel bid 258.90/30 g Erythromycin – generic Erygel (Prestium) 2% gel, soln, pads 2% gel bid 201.00/60 g 250.70/60 g 3%/5% gel bid 253.10/46.6 g 288.40/60 g 0.1%, 0.3% gel, cream, lotion 0.1% gel, cream, lotion; 0.3% gel once/d at bedtime 157.30/45 g 529.70/45 g 0.05%, 0.1% gel, cream 0.1% foam 0.01%, 0.025% gel 0.025%, 0.05%, 0.1% cream 0.05% gel 0.025% gel, cream 0.025%, 0.01% gel 0.025%, 0.05%, 0.1% cream 0.04% gel 0.04%, 0.08%, 0.1% gel once/d in the evening once/d in the evening once/d at bedtime 310.60/30 g 415.20/50 g 128.00/45 g 158.50/45 g 562.40/45 g 192.90/45 g 249.20/45 g 249.60/45 g 451.70/45 g 722.50/45 g Erythromycin/benzoyl peroxide – generic Benzamycin (Valeant) Retinoids Adapalene – generic Differin (Galderma) Tazarotene – Tazorac (Allergan) Fabior (Stiefel) Tretinoin – generic Atralin (Valeant) Avita (Mylan) Retin-A (Valeant) Tretinoin microspheres – generic Retin-A Micro (Valeant) Retinoid/Antimicrobial Combinations Epiduo (Galderma) Epiduo forte Veltin (Stiefel) Ziana (Valeant) once/d at bedtime once/d in the evening once/d at bedtime once/d in the evening 0.1% adapalene/2.5% benzoyl peroxide gel 0.3% adapalene/2.5% benzoyl peroxide gel 0.025% tretinoin/1.2% clindamycin phosphate gel 0.025% tretinoin/1.2% clindamycin phosphate gel once/d once/d in the evening once/d at bedtime 398.10/45 g 398.10/45 g 243.10/30 g 367.00/30 g Approximate WAC for one tube or bottle of the listed size in the lowest available strength When multiple formulations are listed, the cost of the gel is provided WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly January 5, 2016 Reprinted with permission by First Databank, Inc All rights reserved ©2016 www.fdbhealth.com/policies/drug-pricing-policy oxidation of tretinoin and loss of its effectiveness Patients are generally instructed to apply topical retinoids at night because tretinoin is photolabile; adapalene, tazarotene, and the microsphere formulation of tretinoin appear to be more stable when exposed to light SYSTEMIC THERAPY — Oral Antibiotics – Tetracyclines such as doxycycline and minocycline are generally prescribed for moderate to severe inflammatory acne unresponsive to topical drugs In addition to their antibacterial activity, they may have anti-inflammatory effects Adverse effects typically associated with topical retinoids, including dry skin, scaling, photosensitivity, erythema, burning, and pruritus, vary with the formulation, concentration, and frequency of application Tazarotene gel may be more irritating than adapalene Retinoids are teratogenic; even though only small amounts are absorbed systemically, tretinoin and adapalene are classified as category C (teratogenic in rats; no adequate studies in pregnant women) for use during pregnancy Tazarotene is contraindicated during pregnancy (category X) When oral antibiotics are used for treatment of acne they are usually taken for months, which can lead to development of bacterial resistance Resistance is reported more frequently with erythromycin than with other oral antibiotics, and the drug can cause intolerable GI adverse effects Trimethoprim/ sulfamethoxazole should only be used in patients who not tolerate or respond to other oral antibiotics 14 Adverse Effects of Tetracyclines – Tetracyclines can cause mild GI upset and vaginal candidiasis Doxycycline can cause photosensitivity, and hyperpigmentation The Medical Letter ® Vol 58 (1487) February 1, 2016 Table Some Oral Drugs for Acne Drug Antibiotics Doxycycline – generic delayed-release – generic Doryx (Mayne/Actavis) Minocycline – generic Minocin (Valeant) extended-release – generic Solodyn (Valeant) Retinoids Isotretinoin – Absorica5 (Ranbaxy) Amnesteem (Mylan) Claravis (Barr) Myorisan (Akorn) Zenatane (Dr Reddy's) Some Available Formulations Usual Adult Dosage Cost1 20, 50, 100 mg caps, tabs 75, 100, 150 mg tabs 50, 150, 200 mg tabs 50, 75, 100 mg caps, tabs 50, 75, 100 mg caps 45, 90, 135 mg tabs 55, 65, 80, 105, 115 mg tabs 20-100 mg bid 150 mg once/d $108.202,3 422.40 629.70 15.90 1633.70 338.704 1040.404 10, 20, 25, 30, 35, 40 mg caps 10, 20, 40 mg caps 10, 20, 30, 40 mg caps 10, 20, 30, 40 mg caps 10, 20, 30, 40 mg caps 0.5-1 mg/kg/d in divided doses for 15-20 weeks 50-100 mg bid mg/kg once/d 1802.106 551.306 710.706 576.306 592.506 Approximate WAC for 30 days’ treatment with the lowest usual dosage WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly January 5, 2016 Reprinted with permission by First Databank, Inc All rights reserved ©2016 www.fdbhealth.com/policies/drug-pricing-policy May be available at some large discount pharmacies for $4.00 Cost for 50 mg twice daily Cost is the same for all strengths Absorica is not therapeutically equivalent to other isotretinoin products Cost of 30 days’ treatment at 60 mg/day and vertigo can occur with minocycline Extendedrelease minocycline (Solodyn, and generics) is available for once-daily treatment of acne; whether it is less likely than standard minocycline to cause vertigo remains to be established.1 Drug-induced lupus and autoimmune hepatitis can occur with long-term use of minocycline Minocycline may also have a deleterious effect on spermatogenesis; it should not be used by men or women who are attempting to conceive a child Because of their adverse effects on tooth and bone development, none of the tetracyclines should be used during pregnancy or in children