Aprepitant drug interactions

Aprepitant has the potential for numerous drug interactions because it is a substrate, moderate inhibitor, and an inducer of cytochrome isoenzyme CYP3A4 and an inducer of CYP2C9. Aprepitant... 

Verwimp-Hoeks MP, van Herpen CM, Burger DM. Aprepitant quetiapine a clinically significant drug interaction in a patient treated for head and neck cancer. Ann Oncol 2012 23(3) 801-2. 

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. 

The UK manufacturer of aprepitant recommends caution when it is used with antineoplastics that are metabolised by CYP3A4, particularly irinotecan, because of the possibility of increased toxicity with this drug. They also mention that etoposide, vinoreibine, docetaxel, paclitaxel, ifosfamide, imatinib, vinblastine and vincristine, were given without dosage adjustment for potential interactions, but as this was not a formal interaction study they recommend caution. However, with intravenous docetaxel, it appears that no important changes in pharmacokinetics occur, and therefore dosage adjustments are unlikely to be needed for this drug,... 

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. ... 

Paroxetine appears not to interact to a clinically important extent with aluminium hydroxide or food, although absorption may be reduced by large quantities of milk. Concurrent use of paroxetine and aprepitant may slightly reduce the plasma levels of both drugs, but this is probably not clinically significant. 

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