fosaprepitant

Fosaprepitant is an intravenous prodrug of aprepitant, a neurokinin-1 (NK1) receptor antagonist used to prevent chemotherapy-induced nausea and vomiting (CINV). After IV administration, fosaprepitant is rapidly converted by tissue phosphatases to aprepitant, the active compound. By blocking substance P at NK1 receptors in the central nervous system, it helps reduce both the acute and delayed phases of CINV when used as part of a combination antiemetic regimen.

Administration and use: Fosaprepitant is given as a single IV dose before chemotherapy and is typically employed in regimens for highly emetogenic chemotherapy. It is used in adults and is included in broader antiemetic strategies that also rely on a 5-HT3 receptor antagonist and dexamethasone. Because aprepitant inhibits certain drug-metabolizing enzymes, dosing of dexamethasone and other CYP3A4 substrates may need adjustment when fosaprepitant is coadministered.

Pharmacokinetics and interactions: Following infusion, fosaprepitant is rapidly converted to aprepitant, which has a half-life of about 9 to 13 hours and is eliminated primarily through hepatic pathways involving CYP3A4. The interaction with CYP3A4 means that fosaprepitant can alter plasma levels of other drugs metabolized by this enzyme, necessitating consideration of dose modifications for concurrent medications such as dexamethasone and certain chemotherapeutic or supportive agents.

Adverse effects and safety: Common adverse events include fatigue, dizziness, hiccups, constipation, and infusion-site reactions. Hypersensitivity reactions are possible, though rare. Fosaprepitant should be used with caution in patients with known hypersensitivity to NK1 antagonists or related compounds.