Veterinary Medicine - January 2008 - (Page 42)

Systemic antifungals PEER-REVIEWED than they do for mammalian CYP; however, adverse effects in mammals are due in part to inhibiting mammalian CYP. Decreased synthesis of testosterone, cortisol, cholesterol, and androgens may occur during azole administration.1 Terbina ne’s mechanism of action differs from that of the azoles. It inhibits the enzyme squalene epoxidase with a net effect of decreasing ergosterol formation.1 The different mechanism of action results in a different adverse effects pro le (i.e. terbina ne does not inhibit mammalian CYP and has fewer drug-drug interactions) and may be ef cacious in organisms resistant to the azoles. KETOCONAZOLE Ketoconazole is still used regularly in veterinary medicine, but its use is being supplanted by some of the newer antifungal agents. Ketoconazole, which is available as 200-mg tablets, is an affordable alternative when itraconazole or voriconazole are cost-prohibitive. However, ketoconazole has a lower ef cacy against many fungal organisms compared with itraconazole and voriconazole, and ketoconazole may have a greater potential for adverse effects. The typical cost of ketoconazole treatment for a 44-lb (20-kg) dog (10 mg/kg orally twice a day) is about 50¢/day. Potential indications Ketoconazole is typically effective for the systemic treatment of otitis and dermatitis caused by Malassezia species as well as of infections caused by Candida species and dermatophytosis caused by Microsporum canis.1,6 Ketoconazole has also been used to treat blastomycosis, histoplasmosis, cryptococcosis, coccidioidomycosis, and aspergillosis, but itraconazole is considered more ef cacious in treating these infections.1 Pharmacokinetics Ketoconazole is variably absorbed when administered orally in dogs.7 In people, ketoconazole absorption is increased with increased gastric acidity.8 No studies in dogs have examined the effect of a fed or fasted state on ketoconazole absorption, but as in people, it is recommended to be given with food. In people, gastric acid suppression therapy—such as antacids, H2-receptor antagonists (cimetidine, famotidine), or proton pump inhibitors (omeprazole)—decreases ketoconazole absorption. So concurrent administration of these drugs in animals receiving ketoconazole is also not recommended. Ketoconazole is highly protein-bound (> 98%) and penetrates poorly into protected areas such as the central nervous system (CNS), anterior chamber of the eye, and prostate.1 It is eliminated primarily by hepatic metabolism, with a half-life of about two hours in mongrel dogs. No data are available on the pharmacokinetics of ketoconazole in cats. TABLE 1 Recommended Dosages of Antifungals in Dogs and Cats* Drug Ketoconazole Dosage Dogs: 5–15 mg/kg PO q 8-24 h (give with food) Cats: 5–10 mg/kg PO q 8-12 h (give with food) Dogs: 2.5 mg/kg PO q 12 h (give with food) 5 mg/kg PO q 24 h (give with food) 5 mg/kg PO q 24 h for 2 days per week for 3 weeks (Malassezia species infection) (give with food) Cats: 5 mg/kg PO q 12 h (give with food) 10 mg/kg PO q 24 h (give with food) 5–10 mg/kg PO q 24 h for 7 days, then one week on, one week off (dermatophytes) (give with food) Dogs: 10-12 mg/kg PO q 24 h 5 mg/kg PO q 12 h Cats: 10 mg/kg PO q 24 h (typically 50 mg per cat) Dogs: 4–5 mg/kg PO q 12 h Cats: 4–5 mg/kg PO q 12 h Dogs: 5 mg/kg PO q 24 h (give with food) Cats: 5 mg/kg PO q 24 h (give with food) Dogs: 30 mg/kg PO q 24 h (give with food) Cats: 30–40 mg/kg PO q 24 h (give with food) Itraconazole Fluconazole Voriconazole** Drug interactions and adverse effects Since ketoconazole inhibits the metabolizing enzyme CYP3A12 in dogs, adverse effects can occur if it is given concurrently with drugs metabolized by CYP3A12.9 The metabolism of the concomitant drugs is decreased, so toxicosis can occur because of drug accumulation. Ketoconazole also inhibits the pglycoprotein (Pgp) ef ux pump present in numerous anatomical locations, including, but not limited to, the gastrointestinal tract, liver, and blood-brain Posaconazole** Terbinaﬁne * Adapted from Papich MG. Alphabetical drug monographs. In: Saunders handbook of veterinary drugs. 2nd ed. St. Louis, Mo: Saunders, Elsevier, 2007. * * Indicates limited clinical experience in dogs and cats. 42 January 2008 VETERINARY MEDICINE

Table of Contents Feed for the Digital Edition of Veterinary Medicine - January 2008

Veterinary Medicine - January 2008 Contents Digital Extra Letters Toxicology Brief Idea Exchange A Challenging Case: Phimosis in a Young Adult Dog The Indications and Technique for Continuous Ambulatory Electrocardiographic Recording in Dogs A Review of Selected Systemic Antifungal Drugs for Use in Dogs and Cats CE Form Advertiser Index Marketplace/Classifieds Mind Over Miller

Veterinary Medicine - January 2008

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