Ketoconazole inhibits CYP3A4, significantly increasing cyclosporine levels (used therapeutically to reduce cyclosporine dose/cost)
Management: Intentional combination in veterinary practice. Reduce cyclosporine dose by 50-75% when adding ketoconazole. Monitor cyclosporine levels.
Phenobarbital induces hepatic enzymes, reducing ketoconazole levels; ketoconazole may increase phenobarbital levels
Management: Monitor both drug levels. May need dose adjustments.
H2 blockers raise gastric pH; ketoconazole requires acidic environment for absorption
Management: Give ketoconazole at least 2 hours before famotidine, or use fluconazole instead (pH-independent absorption).
H2 blockers reduce gastric acid, decreasing ketoconazole absorption by up to 95%
Management: Separate administration by 2+ hours. Consider switching to fluconazole.
PPIs raise gastric pH, reducing ketoconazole absorption which requires acidic environment
Management: Separate administration by 2 hours. Give ketoconazole with acidic food/drink. Consider itraconazole instead.
PPIs raise gastric pH, markedly reducing ketoconazole bioavailability
Management: Avoid combination. If antifungal needed with PPI therapy, use itraconazole or fluconazole.