What is the typical dosing regimen for Aprepitant (substance P/neurokinin 1 (NK1) receptor antagonist) for the prevention of chemotherapy-induced nausea and vomiting?

Aprepitant Dosing for Chemotherapy-Induced Nausea and Vomiting

For prevention of 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, always in combination with a 5-HT3 antagonist and dexamethasone. 1, 2

Standard Oral Dosing Regimen

• Aprepitant 125 mg orally on Day 1 (administered 1 hour before chemotherapy initiation) 3, 1, 2
• Aprepitant 80 mg orally once daily on Days 2 and 3 (after chemotherapy starts) 3, 1, 2
• If no chemotherapy is administered on Days 2 and 3, give aprepitant in the morning 2
• Aprepitant capsules can be taken with or without food and must be swallowed whole 2

Intravenous Alternative (Fosaprepitant)

Two IV dosing options are available:

• Option 1: Fosaprepitant 115 mg IV on Day 1 only (30 minutes before chemotherapy), followed by oral aprepitant 80 mg on Days 2-3 1
• Option 2: Single-dose fosaprepitant 150 mg IV on Day 1 only (no additional aprepitant needed on Days 2-3), which has been shown to be noninferior to the standard 3-day oral regimen 3, 1

Required Combination Therapy

Aprepitant must always be combined with other antiemetics—never use as monotherapy:

• Day 1: Combine aprepitant with a 5-HT3 antagonist (ondansetron 32 mg IV, granisetron, dolasetron, or palonosetron) plus dexamethasone 12 mg 3, 1, 4
• Days 2-3: Continue dexamethasone 8 mg once daily 3
• Days 3-4 (if using 150 mg IV fosaprepitant): Dexamethasone 8 mg twice daily 3

Critical Dexamethasone Dose Adjustment

• Reduce dexamethasone dose by approximately 50% when used with aprepitant due to CYP3A4 inhibition by aprepitant 3, 1, 2
• Standard dexamethasone dose without aprepitant is 20 mg on Day 1; with aprepitant, use only 12 mg 3, 4

Efficacy by Chemotherapy Type

Highly Emetogenic Chemotherapy (HEC)

• The aprepitant regimen (125/80/80 mg) achieves acute emesis complete response rates of 83-89% and delayed emesis complete response rates of 68-75% 3, 1, 4
• In Latin American trials with high-dose cisplatin, complete response during the entire 5-day period was 62.7% with aprepitant versus 43.3% with standard therapy (P < 0.001) 4

Moderately Emetogenic Chemotherapy (MEC)

• The same aprepitant regimen shows overall complete response of 51% versus 43% with standard therapy (P = 0.015) 3, 1
• In breast cancer patients receiving AC chemotherapy (doxorubicin/cyclophosphamide), aprepitant significantly reduced rescue medication requirements (11% vs. 20%, P = 0.06) and improved quality of life in the vomiting domain 5

Pediatric Dosing (Ages 12 and Older)

• Same dosing as adults: 125 mg on Day 1, then 80 mg on Days 2 and 3 2
• For children 5-18 years receiving highly emetogenic chemotherapy, weight-based dosing has been studied: 80 mg daily for 15-40 kg; 125 mg Day 1 then 80 mg Days 2-3 for 41-65 kg 6

Critical Drug Interactions and Contraindications

Absolute Contraindications

• Never administer aprepitant with pimozide, terfenadine, astemizole, or cisapride due to risk of serious or life-threatening reactions 1, 2

Important CYP3A4 Interactions

• Aprepitant is a substrate, weak-to-moderate inhibitor, and inducer of CYP3A4 1, 2
• Chemotherapy agents affected: docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, and vincristine 1
• Warfarin interaction: Monitor INR closely in the 2-week period (particularly days 7-10) following aprepitant initiation due to decreased INR risk 1, 2

Hormonal Contraceptive Interaction

• Contraceptive efficacy may be reduced during and for 28 days after the last aprepitant dose 1, 2
• Use effective alternative or backup contraception methods during this period 2

Special Considerations for Multiday Chemotherapy

• For multiday chemotherapy regimens that are highly emetogenic with significant delayed nausea risk, aprepitant may be administered during all chemotherapy days plus 2 additional days after chemotherapy completion 3
• In one study of multiday high and moderate emetogenic chemotherapy, complete response rates were 58% and 73%, respectively, when aprepitant was given throughout chemotherapy and for 2 days after 3

Limitations of Use

• Aprepitant has not been studied for treatment of established nausea and vomiting—only for prevention 2
• Chronic continuous administration is not recommended 2