Clarithromycin CYP3A4/5/7 substrate

E Itraconazole. Imatinib is primarily metabolized by the CYP3A4 hepatic enzyme system. Drugs that may inhibit this enzyme (such as ketoconazole, itraconazole, erythromycin, clarithromycin, etc.) may impair clearance of imatinib and result in increased toxicity. Imatinib itself is also a fairly potent inhibitor of the CYP3A4 enzyme and may result in toxicity due to other drugs that are substrates for this enzyme (such as simvastatin, warfarin, benzodiazepines, etc.). The other medications iisted are uniikeiy to affect the function of 0 P3A4 or interact adversely with imatinib. 

The principal cytochrome P450 isoform involved in pimozide oxidation is CYP3A4 catalyzed N-dealkylation (523). CYP1A2 seems to also be involved. Pimozide may also interfere with the metabolism of substrates by CYP2D6. Potentiation of pimozide-induced cardiotoxicity (prolongation of the QT interval) in patients by clarithromycin-induced inhibition by CYP3A4 N-dealkylation has been reported (524). 

The NNRTIs are substrates of the cytochrome P450 isoenzyme CYP3A4, which is inhibited by clarithromycin. Delavirdine is also reported to inhibit CYP3A4, whereas efavirenz and nevirapine induce CYP3A4. Therefore alterations in the metabolism of these drugs by CYP3A4 results in the altered levels seen. 

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