Interactions
The concomitant use of the following medications is contraindicated with ketoconazole tablets:
methadone, disopyramide, dronedarone
irinotecan, lurasidone, colchicine
alprazolam, oral midazolam, oral triazolam
felodipine, ranolazine, tolvaptan, eplerenone
HMG-CoA reductase inhibitors: lovastatin, simvastatin
ergot alkaloids: ergotamine, dihydroergotamine, ergometrine, methylergometrine
Others: cisapride, nisoldipine, dofetilide, pimozideAnd is not recommended:
carbamazepine, phenytoin
gastric acid suppressants: antacids, antimuscarinics, histamine H2 blockers, proton pump inhibitors
sucralfate
rifampin, rifabutin, isoniazid
efavirenz, nevirapineRitonavir is known for increasing activity of the ketoconazole so it is recommended to reduce dosage.There is also a list of drugs which significantly decrease systemic exposure to the ketoconazole and drugs whose systemic exposure is increased by the ketoconazole. Pharmacology
Pharmacodynamics
Antifungal activity
As an antifungal, ketoconazole is structurally similar to imidazole, and interferes with the fungal synthesis of ergosterol, a constituent of fungal cell membranes, as well as certain enzymes. As with all azole antifungal agents, ketoconazole works principally by inhibiting the enzyme cytochrome P450 14α-demethylase (CYP51A1). This enzyme participates in the sterol biosynthesis pathway that leads from lanosterol to ergosterol. Lower doses of fluconazole and itraconazole are required to kill fungi compared to ketoconazole, as they have been found to have a greater affinity for fungal cell membranes. Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including Candida albicans. Experimentally, resistance usually arises as a result of mutations in the sterol biosynthesis pathway. Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step. Multidrug-resistance (MDR) genes can also play a role in reducing cellular levels of the drug.
Oral ketoconazole is now only indicated for use in these countries when the indication is a severe or life-threatening systemic infection and alternatives are unavailable. However, topical ketoconazole, which does not distribute systemically, is safe and widely used still.Ketoconazole HRA was approved for use in the European Union for treatment of Cushings syndrome in November 2013.As of March 2019, oral levoketoconazole (developmental code name COR-003, tentative brand name Recorlev) is phase III clinical trials for the treatment of Cushings syndrome. Oral levoketoconazole may have a lower risk of liver toxicity than oral ketoconazole. Society and culture
Generic names
Ketoconazole is the generic name of the drug and its INN, USAN, BAN, and JAN. Brand names
Ketoconazole has been marketed under a large number of brand names. Availability
Ketoconazole is available widely throughout the world.In 2013, the European Medicines Agencys Committee on Medicinal Products for Human Use (CHMP) recommended that a ban be imposed on the use of oral ketoconazole for systemic use in humans throughout the European Union, after concluding that the risk of serious liver injury from systemic ketoconazole outweighs its benefits. Veterinary use
Ketoconazole is sometimes prescribed as an antifungal by veterinarians for use in pets, often as unflavored tablets that may need to be cut to smaller size for correct dosage. References
External links
"Ketoconazole". Drug Information Portal. U.S. National Library of Medicine.