Inepitant (Aprepitant)

Inepitant, an NK1 receptor antagonist, is employed in the management of nausea and vomiting related to cancer therapy and surgery.

• Chemotherapy‑induced nausea and vomiting: reduces both acute and delayed episodes in patients receiving highly emetogenic regimens.
• Postoperative nausea and vomiting: helps prevent nausea and vomiting after surgical procedures.
• Moderately emetogenic chemotherapy: provides additional control of nausea and vomiting when used with standard antiemetic regimens.

• Aprepitant selectively blocks neurokinin‑1 (NK1) receptors in the central nervous system, inhibiting the binding of substance P. This antagonism prevents the activation of the vomiting centre in the brainstem, thereby reducing the signaling pathways that trigger nausea and vomiting associated with chemotherapy and postoperative stimuli.

Common Side Effects

• Fatigue: feeling of tiredness or lack of energy.
• Constipation: reduced bowel movements or hard stools.
• Hiccups: involuntary diaphragm contractions.
• Dyspepsia: indigestion or stomach discomfort.
• Diarrhea: loose, watery stools.
• Headache: mild to moderate head pain.

Serious or Rare Side Effects

• Severe allergic reaction: rash, swelling, or difficulty breathing.
• Stevens‑Johnson syndrome: serious skin disorder with blistering.
• Elevated liver enzymes: signs of hepatic stress.
• QT interval prolongation: potential cardiac rhythm disturbance.
• Neutropenia: lowered white blood cell count increasing infection risk.

Before initiating therapy, consider the following precautions:

• Assess hepatic function: monitor liver enzymes in patients with liver disease.
• Evaluate cardiac risk: avoid in patients with known prolonged QT interval.
• Review concomitant medications: adjust doses of drugs metabolized by CYP3A4.
• Monitor for hypersensitivity: discontinue if severe allergic reactions occur.
• Use caution in severe renal impairment: dose adjustment may be required.
• Store at room temperature: keep in the original container, protect from moisture and light.

Aprepitant can affect the metabolism of several drugs. Review patient medication lists carefully.

Major Interactions (Avoid)

• Strong CYP3A4 inducers (e.g., rifampin): may reduce aprepitant efficacy.
• Drugs with narrow therapeutic index metabolized by CYP3A4 (e.g., midazolam, warfarin): risk of increased plasma levels.
• QT‑prolonging agents (e.g., quinidine): may increase risk of cardiac arrhythmias.

Moderate Interactions (Monitor Closely)

• Dexamethasone: dose reduction may be needed due to increased exposure.
• Hormonal contraceptives: efficacy may be reduced, advise alternative contraception.
• Other antiemetics (e.g., ondansetron): monitor for additive effects.
• Antifungal azoles (e.g., ketoconazole): may increase aprepitant concentrations.
• Antiretrovirals (e.g., protease inhibitors): monitor for altered drug levels.