Ketoconazole drug interactions

AlbengresE, Tillement JP. Cyclosporin and ketoconazole, drug interaction or therapeutic association IntJ Clin Pharmacol Ther Toxicol (1992) 30,555-70. 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

Itraconazole and ketoconazole (200-800 mg/day orally for 1 year) are effective in 74% to 86% of cases, but relapses are common fluconazole 200-400 mg daily is less effective (64%) than ketoconazole or itraconazole, and relapses are seen in 29% of responders Severe disease Amphotericin B 0.7 mg/kg/day for a minimum total dose of 35 mj kg is effective in 59% to 100% of cases and should be used in patients who require hospitalization or are unable to take itraconazole because of drug interactions, allergies, failure to absorb drug or failure to improve clinically after a minimum of 12 weeks of itiaconazole therapy... 

Because trimetrexate is metabolized by a P450 enzyme system, drugs that induce or inhibit this drug metabolizing enzyme system may elicit important drug interactions that may alter trimetrexate plasma concentrations, which include erythromycin, rifampin, rifabutin, ketoconazole, fluconazole, cimetidine, nitrogen substituted imidazole drugs (eg, clotrimazole, ketoconazole, miconazole). 

The importance of these enzymes for drug interactions is that enzyme inducers and inhibitors may preferentially affect certain isoforms and consequently may only affect the metabolism of selected drugs. For example, ketoconazole has the potential to inhibit the metabolism of drugs metabolised to a great extent by the sub-family 3A (e.g. midazolam) but not of those metabolised by sub-family 1A (e.g. theophylline), 2C (e.g. diazepam), or 2D (e.g. metaprolol). In contrast, although fluconazole is a weaker inhibitor of the sub-family 3A than ketoconazole, it also inhibits the sub-family 2C, and so the interactions of fluconazole differ from those of ketoconazole. 

Administration LEVITRA may require adjustment in patients receiving certain CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, indinavir, and erythromycin) (see Warnings, Precautions Drug Interactions ). For ritonavir, a single dose of 2.5 mg LEVITRA should not be exceeded in a 72-hr period. For indinavir, ketoconazole 400 mg daily, and itraconazole 400 mg daily, a single dose of 2.5 mg LEVITRA should not be exceeded in a 24-hr period. For ketoconazole 200 mg daily, itraconazole 200 mg daily, and erythromycin, a single dose of 5 mg LEVITRA should not be exceeded in a 24-hr period... 

Etravirine is a substrate as well as an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19 it has many therapeutically significant drug-drug interactions (Tables 49-3 and 49-4). Some of the interactions are difficult to predict. For example, etravirine may decrease itraconazole and ketoconazole concentrations but increase voriconazole... 

Drug Interactions Oral contraceptives Ketoconazole Midazalam Possible cytochrome P450 isoform CYP3A4... 

Since indinavir is a substrate as well as an inhibitor of CYP3 A4, numerous and complex drug interactions can occur as described above. Indinavir levels decrease with concurrent use of rifabutin, fluconazole, St. John s wort, and rifampin. Caution is advised with other 3 A4 inducers also, including phenobarbital, phenytoin, carbamezepine, and dexamethasone. Dose reduction of indinavir should be considered if coadministered with delavirdine, ketoconazole, or itraconazole, while an increase in the dose of indinavir is indicated if the drug is coadministered with efavirenz or rifabutin. 

Von Moltke LL, Greenblatt DJ, Cotreaubibbo MM, et al. Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake inhibitor antidepressants, and by qui-nidine and ketoconazole—a model system to predict drug-interactions in vivo. J Pharmacol Exp Ther 1994 268 1278-1283. 

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