Aprepitant

Aprepitant is an antiemetic medication that acts as a selective antagonist of the neurokinin-1 (NK1) receptor. It is used to prevent nausea and vomiting associated with chemotherapy (chemotherapy-induced nausea and vomiting, CINV) and is also employed to reduce postoperative nausea and vomiting in adults. Aprepitant is available in oral form and as fosaprepitant, a water-soluble prodrug for intravenous administration. After administration, fosaprepitant is rapidly converted to aprepitant.

Mechanism and use: By blocking NK1 receptors in the central nervous system, aprepitant inhibits the actions of substance P, a neuropeptide involved in triggering vomiting. In practice, it is used in combination with a 5-HT3 receptor antagonist and dexamethasone as part of a multi-drug regimen tailored to the chemotherapy emetogenic risk.

Pharmacokinetics and interactions: Aprepitant is primarily metabolized by hepatic CYP3A4. It functions as a moderate inhibitor of CYP3A4 and can influence the metabolism of concomitant drugs, including corticosteroids and various chemotherapeutic agents, necessitating dose adjustments for some medications. It can also affect CYP2C9 and CYP2C19 to a lesser extent. These interactions may require monitoring and dose modifications, such as adjusting dexamethasone or other coadministered drugs, and careful monitoring of anticoagulants like warfarin.

Dosing and administration: The intravenous form (fosaprepitant) is typically given as a single-day dose on the first day of chemotherapy. Oral regimens involve multi-day dosing that varies with the chemotherapy regimen and emetogenic risk. The exact schedule is determined by clinical guidelines and the prescriber.

Side effects: Common adverse effects include fatigue, dizziness, hiccups, constipation, and diarrhea. Infusion-site reactions can occur with the IV form.