Antiemetics in Cancer Patients
Primary Recommendation
For cancer patients receiving highly emetogenic chemotherapy (HEC), use triple therapy with an NK₁ receptor antagonist (aprepitant 125 mg PO day 1, then 80 mg days 2-3) plus a 5-HT₃ antagonist (preferably palonosetron 0.25 mg IV day 1) plus dexamethasone (12 mg PO/IV days 1-4, reduced to 50% when combined with aprepitant) to achieve optimal control of chemotherapy-induced nausea and vomiting. 1, 2, 3
For moderately emetogenic chemotherapy (MEC), use a two-drug combination of a 5-HT₃ antagonist plus dexamethasone on day 1, with selective addition of an NK₁ antagonist for high-risk patients (e.g., those receiving carboplatin AUC ≥4 mg/mL per minute). 1
Highly Emetogenic Chemotherapy (HEC) Regimens
Day 1 Protocol (Before Chemotherapy)
Aprepitant: 125 mg PO administered 1 hour prior to chemotherapy, or fosaprepitant 115 mg IV as a 15-minute infusion 30 minutes before chemotherapy 1, 3
5-HT₃ Antagonist (choose one):
Dexamethasone: 12 mg PO or IV (reduced from 20 mg due to CYP3A4 interaction with aprepitant) 1, 2, 3
Days 2-4 Protocol
Aprepitant: 80 mg PO daily on days 2 and 3 (in the morning if no chemotherapy scheduled) 1, 3
Dexamethasone: 8 mg PO or IV daily on days 2-4 1
Optional Adjuncts
Lorazepam: 0.5-2 mg PO/IV/sublingual every 4-6 hours PRN for anticipatory nausea or anxiety 1, 2
H₂ blocker or proton pump inhibitor: Consider for gastric protection 1
Moderately Emetogenic Chemotherapy (MEC) Regimens
Standard Approach (Day 1)
5-HT₃ Antagonist (choose one):
Dexamethasone: 12 mg PO or IV on day 1 only 1
High-Risk MEC (Add NK₁ Antagonist)
For select patients receiving carboplatin AUC ≥4 mg/mL per minute, doxorubicin, epirubicin, ifosfamide, irinotecan, or oxaliplatin: 1
Days 2-3 Protocol (For Delayed Emesis Risk)
Either: Aprepitant 80 mg PO daily (if used on day 1) 1
Or: Dexamethasone 8 mg PO or IV daily 1
Or: Continue 5-HT₃ antagonist (granisetron 1-2 mg PO daily, ondansetron 8 mg PO BID, or dolasetron 100 mg PO daily) 1
Low and Minimal Emetogenic Risk Chemotherapy
Low Risk
Dexamethasone: 12 mg PO or IV daily 1
Minimal Risk
No routine prophylaxis recommended 1
Provide rescue therapy with dopamine antagonist (metoclopramide or prochlorperazine) or 5-HT₃ antagonist as needed 1
Breakthrough/Refractory Nausea and Vomiting
The general principle is to add an agent from a different drug class rather than increasing doses of the same class. 1, 2
First-Line Breakthrough Options
Prochlorperazine: 25 mg suppository PR every 12 hours, or 10 mg PO/IV every 4-6 hours 1, 2
Lorazepam: 0.5-2 mg PO every 4-6 hours 1
Second-Line Breakthrough Options
Granisetron: 1-2 mg PO daily or 1 mg IV 1
Haloperidol: 1-2 mg PO or IV every 6-8 hours for severe refractory cases 1, 2
Radiation-Induced Nausea and Vomiting (RINV)
High Emetic Risk (Upper Abdomen, Total Body Irradiation)
5-HT₃ antagonist before each fraction and for 24 hours after completion of radiotherapy 1, 2
Dexamethasone: 4 mg PO or IV during fractions 1-5 1
Moderate Emetic Risk
5-HT₃ antagonist before each fraction throughout radiotherapy 1
Dexamethasone: 4 mg PO or IV (optional, may offer during fractions 1-5) 1
Low/Minimal Risk
5-HT₃ antagonist or dopamine antagonist as rescue therapy 1
If rescue is used, continue prophylactic therapy until end of radiotherapy 1
Critical Drug Interactions and Safety Considerations
Aprepitant CYP3A4 Interactions
Aprepitant is both a substrate and moderate inhibitor/inducer of CYP3A4, requiring dose adjustments of concomitant medications. 3
Dexamethasone: Reduce dose by 50% when combined with aprepitant (e.g., 12 mg instead of 20 mg on day 1) 1, 2, 3
Contraindicated with pimozide: Risk of life-threatening cardiac arrhythmias 3
Warfarin: Monitor INR closely for 2 weeks (particularly days 7-10) after aprepitant initiation due to decreased INR risk 3
Hormonal contraceptives: Efficacy may be reduced during and for 28 days after aprepitant; use alternative or backup contraception 3
Ondansetron Cardiac Safety
Maximum single IV dose: 16 mg due to QT prolongation risk 4
Avoid: 32 mg single IV doses (FDA warning) 4
5-HT₃ Antagonist Contraindications
- Never use in serotonin syndrome: Can precipitate or worsen the condition 2
Evidence-Based Treatment Selection Algorithm
Step 1: Classify Chemotherapy Emetogenic Risk
Highly emetogenic (e.g., cisplatin ≥50 mg/m², AC regimens): Use triple therapy 1, 2
Moderately emetogenic (e.g., carboplatin, oxaliplatin, cyclophosphamide <1500 mg/m²): Use dual therapy, add NK₁ for high-risk patients 1
Low/minimal risk: Use single agent or rescue therapy only 1
Step 2: Select 5-HT₃ Antagonist
All first-generation 5-HT₃ antagonists (ondansetron, granisetron, dolasetron) have equivalent efficacy for acute emesis. 1, 6
Palonosetron preferred for HEC: Superior delayed-phase control (56.8% vs. first-generation agents) 2, 6
For MEC: Any 5-HT₃ antagonist acceptable; palonosetron no longer specifically preferred over others 1
Step 3: Determine NK₁ Antagonist Need
Selective use for MEC: Add for carboplatin AUC ≥4, anthracyclines, or other high-risk MEC agents 1
Step 4: Adjust Corticosteroid Dosing
With NK₁ antagonist: Dexamethasone 12 mg day 1 (50% reduction) 1, 3
Without NK₁ antagonist: Dexamethasone 20 mg day 1 for HEC, 12 mg for MEC 1
Common Pitfalls to Avoid
Inadequate Acute Phase Control
Failure to control acute emesis (day 1) strongly predicts delayed emesis (days 2-5); optimal day 1 prophylaxis is essential. 7
Insufficient Delayed Phase Coverage
Protection must extend throughout the full period of emetic risk: 4 days for HEC, 3 days for MEC. 1
Consider dexamethasone days 2-3 for MEC agents with known delayed emesis risk 1
Forgetting Drug Interaction Adjustments
Always reduce dexamethasone dose by 50% when combining with aprepitant 1, 3
Counsel patients on reduced contraceptive efficacy for 28 days after aprepitant 3
Using Suboptimal Ondansetron Dosing
Do not use: 8 mg BID or 32 mg once daily for HEC (insufficient efficacy) 4
Correct HEC dosing: 16-24 mg PO or 8-12 mg IV (max 16 mg single IV dose) 1, 4
Neglecting Anticipatory Nausea Prevention
The best treatment for anticipatory nausea is preventing acute and delayed nausea with optimal prophylaxis in prior cycles. 2
Once established, anticipatory nausea is difficult to treat 2
Lorazepam 0.5-2 mg may help but efficacy decreases with repeated cycles 2
Special Populations and Considerations
Concurrent Chemotherapy and Radiotherapy
- Use antiemetic prophylaxis according to the emetogenicity of chemotherapy, unless radiotherapy emetic risk is higher. 1
Pediatric Patients (≥12 Years)
Same dosing as adults for aprepitant, 5-HT₃ antagonists 3
Reduce corticosteroid dose by 50% when combined with aprepitant (specific pediatric corticosteroid dosing not well-established in guidelines) 1, 3
Oral vs. IV Formulations
Oral and IV antiemetic formulations have equivalent efficacy. 1