Cisapride with aprepitant

Aprepitant is a moderate CYP3A4 inhibitor. Aprepitant should not be used concurrently with pimozide or cisapride. Inhibition of cytochrome P450 isoenzyme 3A4 (CYP3A4) by aprepitant could result in elevated plasma concentrations of these drugs, potentially causing serious or life-threatening reactions. Aprepitant is contraindicated in patients who are hypersensitive to any component of the product. 

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. 

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. 

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