Aprepitant Dosing for Chemotherapy-Induced Nausea and Vomiting
For preventing chemotherapy-induced nausea and vomiting, administer oral aprepitant 125 mg on Day 1 (one hour before chemotherapy) followed by 80 mg once daily on Days 2 and 3. 1, 2
Standard Oral Dosing Regimen
The FDA-approved dosing schedule for aprepitant is straightforward and applies to both highly and moderately emetogenic chemotherapy 2:
- Day 1: 125 mg orally, administered 1 hour prior to chemotherapy 1, 2
- Days 2-3: 80 mg orally once daily in the morning 1, 2
- If no chemotherapy is administered on Days 2 and 3, give aprepitant in the morning 2
This regimen can be taken with or without food, and capsules must be swallowed whole 2.
Intravenous Alternative (Fosaprepitant)
Two IV dosing options are available 1:
- Standard regimen: Fosaprepitant 115 mg IV on Day 1 only (30 minutes before chemotherapy), followed by oral aprepitant 80 mg on Days 2-3 1
- Single-dose regimen: Fosaprepitant 150 mg IV on Day 1 only, which eliminates the need for Days 2-3 oral dosing 1
A randomized study demonstrated that the single 150 mg IV dose was noninferior to the standard 3-day oral regimen 1.
Combination Therapy Requirements
Aprepitant is never used as monotherapy. It must be combined with 1:
- 5-HT3 antagonist (ondansetron, granisetron, dolasetron, or palonosetron) on Day 1 1
- Dexamethasone 12 mg on Day 1, with continuation on subsequent days 1
Critical Drug Interaction: Dexamethasone Dose Adjustment
When aprepitant is used with dexamethasone, reduce the dexamethasone dose by approximately 50% due to CYP3A4 inhibition by aprepitant. 1 The standard dexamethasone dose of 20 mg should be reduced to 12 mg when combined with aprepitant 1.
For the higher fosaprepitant dose (150 mg IV), dexamethasone dosing differs: 8 mg orally twice daily on Days 3-4 1.
Efficacy by Chemotherapy Type
Highly Emetogenic Chemotherapy (e.g., Cisplatin ≥70 mg/m²)
The aprepitant regimen (125/80/80 mg) combined with ondansetron and dexamethasone achieved 1:
- Acute emesis control: 83-89% complete response rate 1
- Delayed emesis control: 68-75% complete response rate 1
This represents a significant improvement over standard therapy without aprepitant (acute: 68-78%; delayed: 47-56%) 1.
Moderately Emetogenic Chemotherapy
The same aprepitant regimen showed 1:
- Overall complete response: 51% vs. 43% with standard therapy (P = 0.015) 1
- Acute phase: 88% complete response 3
- Delayed phase: 78% complete response 3
Important Contraindications and Drug Interactions
Absolute contraindications: Do not administer aprepitant with pimozide, terfenadine, astemizole, or cisapride due to risk of serious or life-threatening reactions 1.
Aprepitant is simultaneously a CYP3A4 substrate, moderate inducer, and moderate inhibitor, as well as a CYP2C9 inducer 1. This affects metabolism of:
- Chemotherapy agents: docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, vincristine 1
- Other medications: warfarin (monitor INR closely) 1
Special Populations and Considerations
Pediatric patients ≥12 years: Use the same adult dosing (125 mg Day 1, then 80 mg Days 2-3) 2.
Chronic dosing: No studies demonstrate efficacy or safety of chronic aprepitant dosing, and the drug interaction profile may change with prolonged use 1.
Common Pitfall to Avoid
The most common error is failing to reduce the dexamethasone dose when adding aprepitant to the regimen. Using full-dose dexamethasone (20 mg) with aprepitant leads to excessive corticosteroid exposure and increased infection risk 4. One study noted a 13% infection rate with this combination versus 4% with standard therapy 4.