Aprepitant
Emend
NK-1 (substance P) receptor antagonist
Selective antagonist at central neurokinin-1 receptors in the area postrema and nucleus tractus solitarius. Blocks substance-P-mediated emesis, particularly the delayed phase (24–72 h post-stimulus) where 5-HT3 antagonists lose efficacy.
Indications
- •PONV prophylaxis in high-risk patients (Apfel ≥3, history of motion sickness, opioid-heavy plan)
- •Chemotherapy-induced nausea and vomiting (highly emetogenic regimens)
- •Anticipatory and refractory PONV
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| PONV prophylaxis | 40 mg PO 1–3 h before induction (single dose) | — |
| PONV rescue (off-label IV via fosaprepitant) | 150 mg IV (fosaprepitant) | — |
Pharmacokinetics
PO onset within 1 h. Peak 4 h. Half-life 9–13 h. Hepatic CYP3A4 metabolism (also a moderate CYP3A4 inhibitor at 125 mg dose; 40 mg PONV dose has minimal interaction).
Hemodynamic effects
Minimal direct effect.
Respiratory effects
None directly.
Side effects
- !Headache, fatigue (mild)
- !Constipation
- !Hiccups (5–10%)
- !CYP3A4 interactions — warfarin level may drop ~14%
Contraindications
- ×Concomitant pimozide / cisapride
- ×Severe hepatic impairment (Child-Pugh C)
Clinical pearls
- ★DELAYED PONV: aprepitant covers 24–72 h post-op; ondansetron and dexamethasone wear off by 12 h. Add for high-risk patients with home-discharge plans.
- ★DOES NOT PROLONG QT: unlike most antiemetics — useful in patients on multiple QT-prolonging agents.
- ★OPIOID-HEAVY CASES: Apfel risk multiplied by post-op opioid use. Consider in any patient with planned PCA or chronic opioid history.
- ★COST: ~$50–100/dose — reserve for high-risk; not first-line where ondansetron 4 mg works.
Other drugs in Antiemetics & Related
- Ondansetron
Blocks serotonin receptors at vagal afferents and chemoreceptor trigger zone.
- Metoclopramide
Central D2 antagonism at the chemoreceptor trigger zone (antiemetic). Peripherally, sensitizes upper-GI tissue to acetylcholine → increases lower esophageal sphincter tone, accelerates gastric emptying, speeds duodenal transit. Mild 5-HT4 agonism contributes to prokinesis.
- Droperidol
Potent central D2 antagonism at the chemoreceptor trigger zone. Also α-adrenergic blockade and mild GABA-A facilitation. Highly effective antiemetic and sedative — historically a key component of neuroleptanalgesia.
- Granisetron
Blocks serotonin 5-HT3 receptors (central CTZ + peripheral vagal afferents). More selective + longer-acting than ondansetron.
- Dolasetron
5-HT3 antagonist (prodrug → hydrodolasetron). Effective antiemetic but the most QT/dysrhythmia-prone of the class.
- Promethazine
H1 antihistamine with anticholinergic + antidopaminergic activity → antiemetic + sedation + antihistamine effects.
- Haloperidol
Dopamine D2 antagonist (CTZ) → antiemetic at low doses; antipsychotic/sedating at higher doses.
Suggested reading
- •Stoelting & Hines, Pharmacology & Physiology in Anesthetic Practice, 6e
- •Miller's Anesthesia, 9e
- •FDA package insert
