Ketoconazole

Ketoconazole In Dogs & Cats: Uses, Dosage and Side Effects

Overview

• Broad-spectrum imidazole inhibits the cytochrome systems involved in synthesising ergosterol in fungal cell membranes, resulting in increased cell wall permeability and cellular content leakage.
• In addition, it inhibits the synthesis of cortisol in the adrenal glands of mammals.

Uses of Ketoconazole

• Treatment of Microsporum canis, Microsporum gypseum and Trichophyton mentagrophytes.
• Useful in treating aspergillosis, candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, sporotrichosis and Malassezia dermatitis.
• May be effective in the medical management of hyperadrenocorticism where trilostane and mitotane are not available or tolerated but is generally less effective than either.
• In combination with ciclosporin to reduce the dose of ciclosporin is required.
• Concomitant use of ketoconazole is likely to increase blood levels of cyclosporin.
• Can be used with amphotericin B in systemic fungal disease and in such cases the dose of amphotericin is reduced. See specialist texts for details.

Dose of Ketoconazole in Dogs and Cats

Dogs:

• Antifungal therapy: 5–10 mg/kg p.o. after meals, once daily.
  Several months of treatment may be required depending on the organism and site of infection.
• CNS or nasal infections: Doses up to 40 mg/kg/day are recommended (often in
  conjunction with amphotericin B); ketoconazole does not attain therapeutic levels in the CNS at ‘normal’ doses.
• Hyperadrenocorticism: 5 mg/kg p.o. q12h for 7 days, increasing to 10 mg/kg p.o. q12h for 14 days if no adverse effects are seen.
• Perform an ACTH stimulation test after 14 days and if there is inadequate suppression gradually increase the dose to 15–30 mg/kg p.o. q12h.

Cats:

Not recommended.

Side Effects of Ketoconazole in Dogs and Cats

• Hepatotoxicity.
• Anorexia.
• Vomiting.
• Alterations in hair-coat colour.
• Thrombocytopenia and adrenal insufficiency at high doses.
• Ketoconazole possibly has teratogenic effects.
• Has been associated with cataract development in dogs.

Contraindications of Ketoconazole in Dogs and Cats

• Do not use in animals with hepatic insufficiency.

Some Notes:

• Ketoconazole inhibits cytochrome P450 and may decrease the elimination of drugs metabolized by this system.
• The absorption of ketoconazole may be impaired by drugs that increase the pH of gastric contents, e.g. antacids, antimuscarinics proton pump inhibitors and H2 blockers; stagger dosing of these drugs around ketoconazole dose.
• Ketoconazole extends the activity of methylprednisolone.