CYP3A4 inducers Aprepitant

Drugs that may affect aprepitant include CYP 3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin), CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin), and paroxetine. 

Rifampin, a strong CYP3A4 inducer, effectively decreases the effective half-life of aprepitant three fold. 

Aprepitant is a substrate, a moderate inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9. Use aprepitant with caution in patients receiving concomitant medicinal products, including chemotherapy agents that are primarily metabolized through CYP3A4 (docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine). 

Aprepitant is a substrate for CYP3A4 and an inducer of CYP2C9 and 3A4 (it also has moderate, dose-dependent CYP3A4 inhibitory properties),... 

Aprepitant inhibits the cytochrome P450 isoenzyme CYP3A4 by which midazolam is metabolised, resulting in increased midazolam levels. The pharmacokinetic effect on intravenous midazolam indicate the effects of aprepitant on systemic rather than on intestinal CYP3A4 activity. Aprepitant is also a mild inducer of CYP3A4, however the induction is transient, with maximal effect 3 to 5 days after the end of treatment. 

Rifampicin markedly reduced the AUC of aprepitant, and reduced efficacy would be expected. In the UK, the manufacturer recommends that concurrent use of aprepitant and other strong inducers of CYP3A4 should be avoided. 

Rifampicin is an inducer of the eytoehrome P450 isoenzyme CYP3A4, by which aprepitant is metabolised. Coneurrent use therefore decreases aprepitant levels... 

In the first few days of use, aprepitant 125/80 mg markedly increased levels of midazolam, a probe drug subsfrafe for fhe cyfoehrome P450 isoenzyme CYP3A4. Then, within 2 weeks, a reduction in levels was seen, see Benzodiazepines + Aprepitant , p.721. This effect was not seen with the 40/25 mg dose regimen. Aprepitant is therefore both a dose-dependent inhibitor and an inducer of CYraA4. 

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