Antifungals, Topical Therapeutic Class Review (TCR) November 5, 2019 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage or retrieval system without the express written consent of Magellan Rx Management. All requests for permission should be mailed to: Magellan Rx Management Attention: Legal Department 6950 Columbia Gateway Drive Columbia, Maryland 21046 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. 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FDA-APPROVED INDICATIONS Tinea Tinea Tinea Tinea Cutaneous Drug Other pedis cruris versicolor corporis candidiasis butenafine Relief of itching, burning, and X X -- X -- (Lotrimin Ultra® [OTC])1 cracking butenafine X X X X -- -- (Mentax®)2 ciclopirox 0.77% (Ciclodan® cream/ cream X X X X X -- kit)3,4 ciclopirox 0.77% Seborrheic scalp dermatitis (Loprox®/ cream kit/ gel/ X X X X X (Loprox 1% shampoo only) suspension kit) 5,6,7,8,9 ciclopirox 8% Topical treatment in (Ciclodan solution; Ciclodan immunocompetent patients with kit, Penlac®)10,11 -- -- -- -- -- mild to moderate onychomycosis of fingernails and toenails due to Trichophyton rubrum clotrimazole For discomfort, scaly skin between (Alevazol [OTC], solution)12 X X X the toes or burning feet -- -- (RX only) Relief of itching, burning, and cracking clotrimazole Relief of itching, burning, and (Lotrimin® AF cream X X -- X -- cracking [OTC])13 clotrimazole / Caused by the organism betamethasone Trichophyton rubrum, Trichophyton X X -- X -- (DermacinRx Therazole mentagrophytes, and Pak)14 Epidermophyton floccosum clotrimazole / betamethasone X X -- X -- -- (Lotrisone®, lotion)15 econazole cream16 X X X X X -- econazole cream X X X X X -- (Econasil™ kit)17 econazole foam X -- -- -- -- -- (Ecoza™)18 efinaconazole Topical treatment of 19 onychomycosis of the toenails due (Jublia®) -- -- -- -- -- to Trichophyton rubrum and Trichophyton mentagrophytes ketoconazole20 X X X X X Seborrheic dermatitis ketoconazole (Extina®, Seborrheic dermatitis -- -- -- -- -- Ketodan®)21, 22 Antifungals, Topical Review – November 2019 Page 2 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2019 Magellan Rx Management. All Rights Reserved. FDA-Approved Indications (continued) Tinea Tinea Tinea Tinea Cutaneous Drug Other pedis cruris versicolor corporis candidiasis ketoconazole (Nizoral® shampoo, Nizoral -- -- X -- -- -- A-D shampoo)23 ketoconazole (Xolegel®)24 -- -- -- -- -- Seborrheic dermatitis ketoconazole/skin cleanser Seborrheic dermatitis -- -- -- -- -- 28 (Ketodan Foam Kit®)25 luliconazole Caused by the organism (Luzu™)26 X X -- X -- Trichophyton rubrum and Epidermophyton floccosum miconazole (Desenex [OTC])27 X -- -- -- -- -- miconazole X -- -- X -- -- (Azolen™ [OTC])28 miconazole X -- -- X -- -- (Fungoid®[OTC])29 miconazole X X X X X -- (Lotrimin AF spray [OTC])30 miconazole X X -- -- -- -- (Zeasorb AF® [OTC])31 miconazole/zinc oxide/ Diaper dermatitis (adjunctive white petrolatum -- -- -- -- -- treatment) (Vusion®)32 33 naftifine (Naftin®) X X -- X -- -- nystatin34 -- -- -- -- X -- nystatin/triamcinolone35 -- -- -- -- X -- oxiconazole X (cream X X X -- -- (Oxistat®)36 only) sertaconazole X -- -- -- -- -- (Ertaczo®)37 38 sulconazole (Exelderm®) X X X X -- -- tavaborole Topical treatment of 39 onychomycosis of the toenails due (Kerydin™) -- -- -- -- -- to Trichophyton rubrum or Trichophyton mentagrophytes terbinafine X X X X -- -- (Lamisil® [OTC])40 terbinafine X X - X - -- (Lamisil® AT [OTC])41 Antifungals, Topical Review – November 2019 Page 3 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2019 Magellan Rx Management. All Rights Reserved. FDA-Approved Indications (continued) Tinea Tinea Tinea Tinea Cutaneous Drug Other pedis cruris versicolor corporis candidiasis tolnaftate (Fungoid-D™ X -- -- -- -- -- [OTC])42 tolnaftate (Tinactin® X X X X -- -- [OTC])43 tolnaftate (Lamisil AF X -- -- X -- -- Defense [OTC])44 undecylenic acid -- X X -- X -- (Hongo Cura)45 undecylenic acid (Sponix X X -- -- -- -- Anti-Fungal [OTC])46 Undecyclenic acid/ Relief of itching, burning, and chloroxylenol (Gordochom X -- -- X -- cracking [OTC])47 Janssen announced the discontinuation of Nizoral 2% shampoo (ketoconazole). The last production will be in October 2018 with an expiry date of September 2020. Treatment of tinea versicolor requires a legend topical product while the treatment of tinea pedis, tinea cruris, or tinea corporis may be treated with an over-the-counter (OTC) topical agent. Manufacturer Listing Drug Manufacturer butenafine (Mentax) Mylan butenafine OTC generic, Schering-Plough/Bayer (Lotrimin Ultra OTC) ciclopirox (Ciclodan) Medimetriks ciclopirox (Loprox) generic, Medimetriks/Valeant ciclopirox (Penlac) generic, Valeant clotrimazole OTC (Lotrimin AF) generic; Schering-Plough/Bayer clotrimazole OTC (Alevazol) generic, Capital clotrimazole/betamethasone (Dermacinrx Therazole Pak) Puretek clotrimazole/betamethasone (Lotrisone) generic; Merck econazole generic econazole (Econasil kit) PureTek econazole (Ecoza) Exeltis/Glenmark efinaconazole (Jublia) Valeant Antifungals, Topical Review – November 2019 Page 4 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2019 Magellan Rx Management. All Rights Reserved. Manufacturer Listing (continued) Drug Manufacturer ketoconazole generic ketoconazole (Extina, Ketodan) Mylan, Medimetriks ketoconazole (Nizoral Shampoo, Nizoral A-D Shampoo) generic; Janssen; Johnson & Johnson Consumer ketoconazole (Xolegel) Aqua/Almirall ketoconazole (Ketodan Kit) Medimetriks luliconazole (Luzu) Oceanside, Valeant miconazole OTC generic miconazole (Azolen) OTC Stratus miconazole (Desenex) OTC GlaxoSmithKline Consumer miconazole (Fungoid) OTC Valeant/Pedinol miconazole (Lotrimin AF) OTC Schering-Plough/Bayer/MDS Consumer miconazole (Zeasorb AF) OTC Crown miconazole/zinc oxide/white petrolatum (Vusion) Prestium, Mylan naftifine generic naftifine (Naftin) Sebela nystatin generic nystatin/triamcinolone generic oxiconazole generic oxiconazole (Oxistat) Sandoz sertaconazole (Ertaczo) Valeant sulconazole (Exelderm) Sun/Journey tavaborole (Kerydin)48 Pharmaderm/Sandoz terbinafine (Lamisil AT) OTC generic; Novartis/GSK tolnaftate (Fungoid-D) OTC Valeant tolnaftate (Tinactin) OTC Schering-Plough/Bayer tolnaftate (Lamisil AF) OTC Novartis/GSK tolnaftate OTC generic undecylenic acid (Hongo Cura) solution OTC Kramer undecylenic acid (Sponix Anti-Fungal) solution OTC BioRx undecyclenic acid/chloroxylenol (Gordochom) solution OTC Gordon Antifungals, Topical Review – November 2019 Page 5 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2019 Magellan Rx Management. All Rights Reserved. OVERVIEW Tinea cruris, corporis, and pedis, named for the body sites involved, are superficial fungal infections (dermatophytosis) caused by 3 genera of dermatophytes: Trichophyton, Microsporum, and Epidermophyton.49 These dermatophytes are a homogenous group of fungi that live on the keratin of the stratum corneum, nails, and hair. The estimated lifetime risk of acquiring tinea infections is between 10% and 20%.50 Dryness of the skin’s outer layer discourages colonization by microorganisms and shedding of epidermal cells keeps many microbes from establishing residence. With inhibition or failure of the skin’s protective mechanisms, cutaneous infection may occur with subsequent pruritus, redness, and scaling. Since dermatophytes require keratin for growth, they are restricted to hair, nails, and superficial skin; therefore, most can be treated with topical antifungal medications.51 Tinea pedis (athlete’s foot) is 1 of the most common superficial fungal infections of the skin and is most often caused by the dermatophytes Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum.52 Affected skin is usually pruritic with scaling plaques on the soles extending to the lateral aspect of the feet and interdigital spaces. Tinea cruris is a dermatophyte infection of the groin (jock itch) also caused by T. rubrum, T. mentagrophytes, and E. floccosum. This condition affects the skin of the medial and upper parts of the thighs, usually bilaterally, with severe pruritus. Tinea corporis (ringworm on the skin) refers to