fosaprepitant
Brand: Emend IV
Prototype: aprepitant
Drug Class: neurokinin-1 receptor antagonist
Drug Family: antiemetic
Subclass: NK1 antagonist prodrug (IV formulation)
Organ Systems: gastrointestinal
Mechanism of Action
Prodrug of aprepitant; rapidly converted to aprepitant after IV administration. Aprepitant selectively antagonizes NK1 receptors in the brainstem vomiting center and GI tract, blocking substance P-mediated emesis, particularly the delayed phase of CINV.
NK1 (substance P) receptors in brainstem
Indications
- prevention of acute and delayed CINV (combination therapy)
- prevention of PONV
Contraindications
- concurrent use with pimozide (CYP3A4 inhibition increases pimozide risk)
Adverse Effects
Common
- fatigue
- hiccups
- diarrhea
- infusion site reactions
Serious
- infusion-site phlebitis/thrombophlebitis (less common with IV than older formulations)
- Stevens-Johnson syndrome (rare)
Pharmacokinetics (ADME)
| Absorption | IV prodrug; converted to aprepitant within 30 minutes |
| Distribution | aprepitant: >95% protein bound |
| Metabolism | aprepitant metabolized via CYP3A4 (major), CYP1A2 and CYP2C19 (minor) |
| Excretion | renal (<5% unchanged); primarily fecal as metabolites |
| Half-life | aprepitant: 9–13 hours |
| Onset | within 30 minutes (IV conversion) |
| Peak | end of infusion |
| Duration | 24 hours |
| Protein Binding | >95% |
| Vd | 70 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| pimozide | CYP3A4 inhibition increases pimozide exposure; risk of fatal arrhythmia | contraindicated |
| dexamethasone | CYP3A4 inhibition increases dexamethasone levels; reduce dexamethasone dose by 50% | major |
| warfarin | CYP3A4 induction by aprepitant decreases warfarin levels 3–5 days after treatment | moderate |
Nursing Considerations
- Administer as a 30-minute IV infusion 30 minutes before chemotherapy.
- Reduce dexamethasone dose by 50% when used in CINV combination regimens due to CYP3A4 interaction.
- Monitor INR in patients on warfarin for 2 weeks after aprepitant/fosaprepitant use; warfarin levels may decrease.
- Observe infusion site for thrombophlebitis; flush line thoroughly after administration.
Clinical Pearls
- Fosaprepitant provides the convenience of IV administration in one dose compared to the 3-day oral aprepitant regimen, improving compliance in the clinical setting.
- Blocking NK1 receptors specifically targets the delayed phase of CINV (24–120 hours post-chemo), which is not well-controlled by 5-HT3 antagonists alone.
Safety Profile
Pregnancy generally-safe
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.