Aprepitant — Drug Monograph

Brand names: Emend

Drug class: Supportive Care Agent

Mechanism of Action

Selective antagonist of human substance P/neurokinin 1 (NK1) receptors. Substance P (encoded by the TAC1 gene) is a neuropeptide that binds NK1 receptors in the brainstem and peripheral nervous system, playing a key role in the delayed phase of chemotherapy-induced nausea and vomiting. Unlike 5-HT3 antagonists, aprepitant primarily prevents delayed CINV (24–120 hours). Acts synergistically with 5-HT3 antagonists and dexamethasone.

FDA Indications

• Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC), including cisplatin-based regimens — in combination with other antiemetics
• Prevention of nausea and vomiting associated with moderately emetogenic chemotherapy (MEC) — in combination with other antiemetics
• Prevention of postoperative nausea and vomiting (PONV)

Common Side Effects

• Fatigue/asthenia
• Nausea (paradoxical, mild)
• Constipation
• Hiccups
• Diarrhea
• Anorexia

Clinical Pearl

Aprepitant was the first NK1 antagonist approved for CINV and transformed the prevention of delayed nausea. ASCO and NCCN guidelines mandate NK1 antagonist inclusion in all HEC prophylaxis regimens. The triple regimen (5-HT3 antagonist + NK1 antagonist + dexamethasone) is standard for HEC; adding olanzapine makes a potent 4-drug regimen. The key CYP3A4 interaction with dexamethasone requires dose reduction of dexamethasone to avoid over-immunosuppression — a commonly missed clinical step.

Related Therapies & Mechanisms

• Avatrombopag (Doptelet) — Supportive Care Agent
• Darbepoetin Alfa (Aranesp) — Supportive Care Agent
• Defibrotide (Defitelio) — Supportive Care Agent
• Denosumab (Xgeva (oncology — 120 mg SC q4w)) — Supportive Care Agent