Fosaprepitant Dosing and Administration
For adults receiving highly emetogenic chemotherapy (HEC), administer fosaprepitant 150 mg intravenously over 20-30 minutes on Day 1 only, approximately 30 minutes before chemotherapy, combined with a 5-HT3 antagonist and dexamethasone 12 mg (reduced from 20 mg due to drug interaction). 1
Adult Dosing Regimens
Highly Emetogenic Chemotherapy (HEC)
- Day 1: Fosaprepitant 150 mg IV over 20-30 minutes + Dexamethasone 12 mg orally + 5-HT3 antagonist
- Days 2-4: Dexamethasone 8 mg orally twice daily (morning on Day 2, then twice daily Days 3-4)
- No fosaprepitant needed after Day 1 1
The dexamethasone dose is reduced by 50% (from 20 mg to 12 mg on Day 1, from 16 mg to 8 mg on Days 2-4) because fosaprepitant inhibits CYP3A4 metabolism of dexamethasone, leading to higher steroid concentrations 1.
Moderately Emetogenic Chemotherapy (MEC)
- Day 1 only: Fosaprepitant 150 mg IV over 20-30 minutes + Dexamethasone 12 mg orally + 5-HT3 antagonist
- No additional days of antiemetics required 1
This single-day regimen for MEC is simpler than HEC and reflects the lower emetogenic risk.
Pediatric Dosing (≥6 months, ≥6 kg)
Ages 12-17 years
- 150 mg IV over 30 minutes on Day 1 1
Ages 2 to <12 years
- 4 mg/kg IV (max 150 mg) over 60 minutes on Day 1 1
Ages 6 months to <2 years
- 5 mg/kg IV (max 150 mg) over 60 minutes on Day 1 1
Critical requirement: Pediatric fosaprepitant must be administered through a central venous catheter 1. If using a 3-day regimen, give fosaprepitant IV on Day 1, then switch to oral aprepitant on Days 2-3.
Key Administration Details
Infusion timing: Complete the infusion approximately 30 minutes before chemotherapy begins 1.
Infusion duration:
- Adults: 20-30 minutes 1
- Pediatrics 12-17 years: 30 minutes 1
- Pediatrics 6 months to <12 years: 60 minutes 1
Stability: Reconstituted solution is stable for 24 hours at room temperature (≤25°C). Discard unused portions 1.
Contraindications and Precautions
Absolute Contraindications
- Hypersensitivity to fosaprepitant, aprepitant, polysorbate 80, or any component 1
- Concurrent use with pimozide (risk of QT prolongation and torsades de pointes due to CYP3A4 inhibition) 1
Major Warnings
Hypersensitivity reactions including anaphylaxis and anaphylactic shock have been reported. Patients should seek immediate medical attention for hives, rash, itching, skin peeling, flushing, difficulty breathing/swallowing, dizziness, rapid/weak heartbeat, or feeling faint 1.
Infusion site reactions are the dose-limiting toxicity, ranging from pain and erythema to thrombophlebitis, necrosis, and vasculitis. This risk is particularly elevated when fosaprepitant is co-administered with anthracyclines 1, 2. Patients should report new or worsening symptoms at or near the infusion site 1.
Drug Interactions Requiring Dose Adjustments
Dexamethasone: Reduce dose by 50% on Days 1-2 when used with fosaprepitant due to CYP3A4 inhibition 1.
Warfarin: Monitor INR closely during the 2-week period after each fosaprepitant dose, particularly at 7-10 days, as fosaprepitant affects warfarin metabolism 1.
Hormonal contraceptives: Efficacy may be reduced. Use effective alternative or backup contraception (condoms, spermicides) during treatment and for 1 month after fosaprepitant administration 1.
Important Clinical Considerations
The newer IV formulation of aprepitant (fosaprepitant) does not contain polysorbate 80, which was associated with hypersensitivity reactions in older formulations 3. This represents a safety improvement.
Fosaprepitant has NOT been studied for treatment of established nausea and vomiting—only for prevention 1. Do not use it to treat breakthrough symptoms.
For multi-day cisplatin regimens (e.g., 3-5 consecutive days), emerging evidence suggests that multiple doses of fosaprepitant may be more effective than single-dose administration 4, 5, 6, though this is not yet reflected in FDA labeling. The standard FDA-approved approach remains single-dose on Day 1 with continuation of oral aprepitant on subsequent days if needed 1.
Storage: Vials must be refrigerated at 2-8°C (36-46°F) 1.