Emend (Aprepitant) Dosing Regimens
Chemotherapy-Induced Nausea and Vomiting (CINV)
For highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC), administer aprepitant 125 mg orally 1 hour before chemotherapy on day 1, followed by 80 mg orally on days 2 and 3, in combination with a 5-HT3 antagonist and dexamethasone. 1
Day 1 Regimen (Before Chemotherapy)
- Aprepitant 125 mg orally 1 hour before chemotherapy 2, 1
- 5-HT3 antagonist (ondansetron 8 mg IV, granisetron 1 mg IV, or palonosetron 0.25 mg IV) 3, 4
- Dexamethasone 12 mg orally or IV (reduced from 20 mg due to CYP3A4 interaction with aprepitant) 2, 3, 4
Days 2 and 3 (Post-Chemotherapy)
- Aprepitant 80 mg orally once daily in the morning 2, 1
- Dexamethasone 8 mg orally once daily (for HEC only; may be given twice daily on days 2-4 depending on regimen) 2, 4
- If no chemotherapy is administered on days 2-3, give aprepitant in the morning 1
Alternative IV Formulation
- Fosaprepitant 115 mg IV on day 1 only (30 minutes before chemotherapy), followed by oral aprepitant 80 mg on days 2-3 2, 3
- Fosaprepitant 150 mg IV as a single-dose alternative on day 1 eliminates the need for oral aprepitant on days 2-3, but requires dexamethasone 8 mg orally twice daily on days 3-4 2
Administration Considerations
- Aprepitant capsules can be taken with or without food 1
- Swallow capsules whole; do not crush or open 1
- The regimen is effective for both initial and repeat cycles of chemotherapy 1, 5
Multiday Chemotherapy Regimens
- For multiday highly or moderately emetogenic chemotherapy, continue the 3-drug regimen (aprepitant, 5-HT3 antagonist, dexamethasone) daily during chemotherapy, then aprepitant 80 mg and dexamethasone for 2 additional days after chemotherapy completion 2
- This approach achieved complete response rates of 58% for highly emetogenic and 73% for moderately emetogenic multiday regimens 2
Postoperative Nausea and Vomiting (PONV)
For prevention of PONV in adults, administer a single dose of aprepitant 40 mg orally within 3 hours prior to induction of anesthesia. 1
PONV Dosing Details
- Single dose of 40 mg is the FDA-approved regimen 1
- Administer within 3 hours before anesthesia induction 1
- This single dose was superior to ondansetron 4 mg IV for preventing vomiting at 24 and 48 hours post-surgery (84% vs 71% at 24 hours, p<0.001) 6
- Can be administered with or without food 1
Critical Drug Interactions and Warnings
Dexamethasone Dose Reduction
- Reduce dexamethasone dose by approximately 50% when co-administered with aprepitant due to CYP3A4 inhibition 2, 3, 4
- Standard dexamethasone dose without aprepitant would be 20 mg on day 1 and 16 mg on days 2-4; with aprepitant, use 12 mg on day 1 and 8 mg on days 2-3 2
Warfarin Monitoring
- Monitor INR closely in the 2-week period (particularly days 7-10) following aprepitant initiation, as aprepitant induces CYP2C9 and can decrease INR 1
Hormonal Contraceptive Efficacy
- Aprepitant reduces efficacy of hormonal contraceptives during treatment and for 28 days after the last dose 1
- Advise patients to use effective alternative or backup contraception during this period 1
Contraindications
- Do not use with pimozide due to risk of QT prolongation from elevated pimozide levels 1
- Contraindicated in patients with known hypersensitivity to aprepitant 1
CYP3A4 Interactions
- Aprepitant is a substrate, weak-to-moderate inhibitor, and inducer of CYP3A4 1
- Avoid strong CYP3A4 inducers (e.g., rifampin) as they may reduce aprepitant efficacy 1
- Use caution with strong CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) as they may increase aprepitant levels and adverse effects 1
Common Adverse Effects
CINV Prevention
- Most common (≥3%): fatigue (13%), diarrhea (9%), asthenia (7%), dyspepsia (7%), abdominal pain (6%), hiccups (5%), decreased white blood cell count (4%), dehydration (3%), increased ALT (3%) 1, 5
PONV Prevention
- Most common (≥3%): constipation and hypotension 1