CYP3A4 substrates Aprepitant

Aprepitant may be affected by paroxetine, CYP2C9 substrates (eg, phenytoin, tolbutamide, warfarin), CYP3A4 substrates (eg, alprazolam, cisapride, dexamethasone, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, methylprednisolone, midazolam, paclitaxel, pimozide, triazolam, vinblastine, vincristine, vinorelbine), and oral contraceptives. 

Although not assessed, this marked leduetion in aprepitant levels could result in reduced eflieaey. In the UK, the manufacturer recommends that concurrent use of aprepitant and strong indueers of CYP3A4, such as rifampicin, be avoided. They also name phenytoin (see also Aprepitant + CYP2C9 substrates , above), carbamazepine, and phenobarbital, and... 

Aprepitant can increase the levels of CYP3A4 substrates in the short-term, then reduce them within 2 weeks. Caution is advised. Note that the manufacturers of aprepitant specifically contraindicate its concurrent use with pimozide, terfenadine, astemizole or cisapride. 

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),... 

After absorption, aprepitant is bound extensively to plasma proteins (>95%) it is extensively metabolized, primarily by hepatic CYP3A4, and is excreted in the stool its t is 9—13 hours. Aprepitant has the potential to interact with other substrates of CYP3A4, requiring adjustment of other drugs, including dexamethasone, methylprednisolone (whose dose may need to be reduced by 50%), and warfarin. Aprepitant is contraindicated in patients on cisapride (see above) or pimozide, in whom life-threatening ventricular tachyarrthmias has been reported. 

Both aprepitant and diitiazem are substrates and inhibitors of the cytochrome P450 isoenzyme CYP3A4, therefore they eaeh inhibit the other drugs metabolism. The clinical relevance of this interaction is uncertain, but the manufacturers recommend caution with diitiazem and other moderate inhibitors of CYP3A4. ... 

Corticosteroids noted an increase in plasma levels of dexamethasone or methylprednisolone when given concurrently with aprepitant. Corticosteroids are substrates for CYP3A4 and the inhibition of this enzyme by high-dose aprepitant leads to raised plasma levels of corticosteroids. 

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