aprepitant
Brand: Emend
Prototype Drug
Drug Class: antiemetic
Drug Family: antiemetic
Subclass: neurokinin-1 (NK1) receptor antagonist
Organ Systems: gastrointestinal
Mechanism of Action
NK1 receptor antagonist blocking substance P action centrally and peripherally; most effective for delayed CINV (24-120h post-chemo); used in triple antiemetic regimens.
neurokinin-1 (substance P) receptor
Indications
- highly emetogenic chemotherapy CINV (prevention)
- post-operative nausea/vomiting (prevention)
Contraindications
- concurrent pimozide
- concurrent cisapride
Adverse Effects
Common
- fatigue
- hiccups
- diarrhea
- constipation
Serious
- severe hypersensitivity
Pharmacokinetics (ADME)
| Absorption | ~60-65% oral |
| Distribution | large Vd |
| Metabolism | extensive hepatic CYP3A4 and CYP1A2 |
| Excretion | renal negligible, fecal |
| Half-life | 9-13 hours |
| Onset | 3-5 hours |
| Peak | 4 hours |
| Duration | delayed CINV ~120h |
| Protein Binding | 97% |
| Vd | 66-99 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP3A4 inhibitors | increase aprepitant levels | major |
| CYP3A4 substrates (warfarin, oral contraceptives) | aprepitant inhibits CYP3A4 — increases their levels | major |
| oral contraceptives | CYP3A4 induction 2 weeks after last dose — reduces OC efficacy; use backup contraception | major |
Nursing Considerations
- Triple antiemetic regimen: aprepitant + ondansetron + dexamethasone
- Use backup contraception for 1 month after last dose (CYP3A4 induction reduces OC efficacy)
- Monitor INR if on warfarin
- Take 1 hour before chemotherapy on day 1; continue day 2 and 3
Clinical Pearls
- Prevents delayed CINV (peaks 48-72h post-chemo) — ondansetron alone insufficient
- CYP3A4 net inhibitor then inducer over time: immediate inhibition, then induction — reduces OC efficacy with prolonged use
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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