Recommended Regimen for Emend (Aprepitant) and Granisetron in Chemotherapy-Induced Nausea and Vomiting Prevention
For highly or moderately emetogenic chemotherapy, combine aprepitant 125 mg orally on Day 1 (one hour before chemotherapy) followed by 80 mg once daily on Days 2-3, with granisetron 2 mg orally once daily (or 1 mg IV) on Day 1, plus dexamethasone 12 mg on Day 1 (reduced by 50% due to aprepitant's CYP3A4 interaction). 1, 2
Standard Triple-Therapy Regimen
Day 1 (Before Chemotherapy):
- Aprepitant 125 mg orally (1 hour before chemotherapy) 2
- Granisetron 2 mg orally OR 1 mg IV 1
- Dexamethasone 12 mg (reduced from 20 mg due to aprepitant interaction) 1, 2
Days 2-3 (Post-Chemotherapy):
- Aprepitant 80 mg orally once daily 1, 2
- Dexamethasone 8 mg once daily (continue for delayed emesis) 1
- Granisetron is typically not continued beyond Day 1 for standard regimens 1
Efficacy Data Supporting This Combination
The aprepitant-based triple therapy regimen demonstrates superior outcomes compared to standard therapy:
- For highly emetogenic chemotherapy: Complete response rates of 83-89% for acute emesis and 68-75% for delayed emesis when aprepitant is combined with a 5-HT3 antagonist and dexamethasone 2
- For moderately emetogenic chemotherapy: Overall complete response of 51% versus 43% with standard therapy (P = 0.015) 2, 3
- The combination significantly reduces rescue medication requirements (11% vs 20%, P = 0.06) and improves quality of life, particularly in the vomiting domain 4
Critical Drug Interaction Warning
When combining aprepitant with corticosteroids, the dexamethasone dose must be reduced by approximately 50% because aprepitant inhibits CYP3A4 metabolism. 1, 2 This means using 12 mg instead of 20 mg on Day 1, and 8 mg instead of higher doses on subsequent days.
Alternative IV Formulation Option
For patients unable to take oral medications, fosaprepitant offers two IV alternatives:
- Fosaprepitant 115 mg IV on Day 1 only (30 minutes before chemotherapy), followed by oral aprepitant 80 mg on Days 2-3 2
- Single-dose fosaprepitant 150 mg IV on Day 1 only (noninferior to standard 3-day oral regimen) 2
Important Contraindications
Absolute contraindications include concurrent use with pimozide, terfenadine, astemizole, or cisapride due to risk of serious or life-threatening reactions. 2 Aprepitant also affects metabolism of multiple chemotherapy agents including docetaxel, paclitaxel, etoposide, irinotecan, and warfarin. 2
Management of Breakthrough Symptoms
If nausea or vomiting occurs despite this regimen:
- Add dopamine antagonists (metoclopramide 20-30 mg or prochlorperazine 10-20 mg) to the existing regimen rather than increasing doses 1
- Consider adding lorazepam 1-2 mg for anticipatory nausea 1
Tolerability Profile
This combination is generally well tolerated, with the aprepitant-based regimen showing a significantly lower incidence of neutropenia (35.5% vs 53.2%, P = 0.0468) and grade ≥3 neutropenia (21.0% vs 45.2%, P = 0.0042) compared to standard regimens. 4