Aprepitant Dosing
For chemotherapy-induced nausea and vomiting (CINV), administer aprepitant 125 mg orally on day 1 (one hour before chemotherapy), followed by 80 mg orally on days 2 and 3, combined with a 5-HT3 antagonist and dexamethasone; for postoperative nausea and vomiting (PONV), give a single 40 mg oral dose within 3 hours prior to anesthesia induction. 1
Chemotherapy-Induced Nausea and Vomiting (CINV)
Highly Emetogenic Chemotherapy (HEC)
The standard regimen for HEC (including cisplatin-based regimens) consists of:
Day 1:
- Aprepitant 125 mg orally (1 hour before chemotherapy)
- 5-HT3 antagonist (per product labeling)
- Dexamethasone 12 mg orally or IV (30 minutes before chemotherapy)
Days 2-3:
- Aprepitant 80 mg orally (in morning if no chemotherapy scheduled)
- Dexamethasone 8 mg orally or IV
Day 4:
- Dexamethasone 8 mg orally or IV only
The dexamethasone dose is reduced by 50% when combined with aprepitant due to a drug-drug interaction where aprepitant inhibits CYP3A4, increasing dexamethasone plasma concentrations approximately twofold 3, 4. This three-drug regimen achieves complete response rates of 68-89% for acute emesis and 56-75% for delayed emesis, significantly superior to two-drug regimens 4.
Moderately Emetogenic Chemotherapy (MEC)
For MEC, including anthracycline-cyclophosphamide (AC) regimens:
Day 1:
- Aprepitant 125 mg orally (1 hour before chemotherapy)
- 5-HT3 antagonist (per product labeling)
- Dexamethasone 12 mg orally or IV
Days 2-3:
- Aprepitant 80 mg orally (in morning if no chemotherapy scheduled)
- No dexamethasone required for MEC (unlike HEC)
For AC regimens specifically, this three-drug approach is strongly recommended with high-level evidence, achieving complete response rates of approximately 51% versus 43% with standard two-drug regimens 2, 3.
Intravenous Alternative: Fosaprepitant
Fosaprepitant (IV formulation) can replace oral aprepitant on day 1 only:
- Standard dose: 115 mg IV on day 1, then oral aprepitant 80 mg on days 2-3
- High dose: 150 mg IV on day 1 as a single dose (no oral aprepitant needed on days 2-3)
When using the 150 mg fosaprepitant single-dose regimen, dexamethasone dosing changes to 8 mg orally twice daily on days 3-4 4. This single-dose fosaprepitant regimen was shown to be non-inferior to the standard 3-day oral aprepitant regimen 4.
Multi-Day Chemotherapy Regimens
For multi-day chemotherapy (e.g., 5-day cisplatin regimens):
- Aprepitant 125 mg on day 1
- Aprepitant 80 mg on days 2-3 (standard)
- Limited data supports extending to days 4-5 for prolonged regimens 4, 5
One small phase III study in germ cell tumors used aprepitant 125 mg on day 3, then 80 mg on days 4-7 with good efficacy 5. However, chronic continuous dosing is not recommended as the drug interaction profile may change 3, 1.
Postoperative Nausea and Vomiting (PONV)
Single dose: 40 mg orally within 3 hours prior to induction of anesthesia 1
This single-dose regimen was effective in preventing PONV in adults undergoing abdominal surgery 6. Pediatric studies support similar dosing strategies adjusted for weight 7.
Pediatric Dosing
Ages 12-17 Years (who can swallow capsules)
Use adult dosing:
- Day 1: 125 mg orally
- Days 2-3: 80 mg orally
- Reduce concomitant corticosteroid dose by 50% 1
Ages 6 Months to <12 Years
Weight-based dosing:
- Day 1: 3.0 mg/kg (maximum 125 mg)
- Days 2-3: 2.0 mg/kg (maximum 80 mg)
A landmark pediatric phase 3 trial demonstrated that aprepitant plus ondansetron (with or without dexamethasone) achieved 51% complete response in the delayed phase versus 26% with control (p<0.0001) 8. The regimen was well-tolerated with safety profiles similar to control groups.
Important pediatric consideration: Recent evidence suggests the dexamethasone dose reduction should be 30% (not 50%) when given intravenously with aprepitant in children, as the drug interaction is less pronounced than in adults 10. This differs from adult guidelines and warrants attention.
Renal and Hepatic Impairment
No dose adjustment is required for mild to moderate renal or hepatic impairment based on pharmacokinetic studies 6, 11. Aprepitant has not been studied in severe hepatic impairment or end-stage renal disease requiring dialysis, so use caution in these populations.
Critical Drug Interactions
Aprepitant is simultaneously a CYP3A4 substrate, moderate inhibitor, and moderate inducer, plus it induces CYP2C9 3.
Contraindicated combinations:
- Pimozide, terfenadine, astemizole, cisapride (risk of serious/life-threatening reactions) 3
Chemotherapy agents metabolized by CYP3A4 requiring caution:
- Docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, vincristine 3
Other significant interactions:
- Warfarin: Monitor INR closely, particularly days 7-10 after aprepitant initiation
- Oral contraceptives: Efficacy may be reduced; use backup contraception during and for 1 month after aprepitant
- Dexamethasone/methylprednisolone: Reduce dose by 50% (as noted above)
The oral formulation has more significant drug interactions than IV fosaprepitant due to first-pass metabolism 3.
Administration Instructions
- Aprepitant capsules can be taken with or without food
- Swallow capsules whole; do not open or crush
- If chemotherapy is not given on days 2-3, administer aprepitant in the morning 1
Common Pitfalls to Avoid
- Do not use aprepitant for established nausea/vomiting - it is for prevention only 1
- Do not use chronic continuous dosing - only studied for 3-day regimens 3, 1
- Do not forget to reduce dexamethasone dose by 50% when using aprepitant (30% for IV dexamethasone in children) 1, 10
- Do not repeat palonosetron on days 2-3 - single dose on day 1 is sufficient 4, 5
- Do not administer fosaprepitant at intervals <1 week or rolapitant at intervals <2 weeks due to extended half-lives 5