What are the best anti-emetic medications?

Best Anti-Emetic Medications

For chemotherapy-induced nausea and vomiting (CINV), the most effective regimen is a combination of a 5-HT3 antagonist (preferably palonosetron), an NK1 antagonist (aprepitant or fosaprepitant), and dexamethasone, with the specific combination determined by the emetogenic risk of the chemotherapy. 1

High Emetogenic Risk Chemotherapy (e.g., cisplatin ≥50 mg/m², AC regimens)

Triple therapy is mandatory:

• Aprepitant 125 mg PO on day 1 (or fosaprepitant 115 mg IV), followed by aprepitant 80 mg PO on days 2-3 1
• Palonosetron 0.25 mg IV on day 1 (preferred 5-HT3 antagonist, category 2B) 1, 2
  • Alternative 5-HT3 antagonists if palonosetron unavailable: ondansetron 16-24 mg PO or 8-12 mg IV, granisetron 2 mg PO or 0.01 mg/kg IV, or dolasetron 100 mg PO/IV 1
• Dexamethasone 12 mg PO/IV on days 1-4 1
• Optional: Lorazepam 0.5-2 mg PO/IV/sublingual every 4-6 hours PRN 1

The combination of ondansetron plus dexamethasone has been demonstrated superior to ondansetron monotherapy and to standard regimens with metoclopramide for acute high-dose cisplatin-induced emesis 3, 4.

Moderate Emetogenic Risk Chemotherapy (e.g., carboplatin, oxaliplatin, doxorubicin)

Day 1 regimen:

• Palonosetron 0.25 mg IV (preferred, given superior efficacy for delayed emesis) 1, 2
  • Palonosetron demonstrates superiority over first-generation 5-HT3 antagonists for both acute and delayed emesis (24-120 hours post-chemotherapy) 2
• Dexamethasone 12 mg PO/IV 1
• Add aprepitant 125 mg PO (or fosaprepitant 115 mg IV) for select higher-risk moderate agents (carboplatin, cisplatin <50 mg/m², doxorubicin, epirubicin, ifosfamide, irinotecan, methotrexate) 1

Days 2-3 options (choose one):

• Aprepitant 80 mg PO daily (if used on day 1) 1
• OR Dexamethasone 12 mg PO/IV daily 1
• OR 5-HT3 antagonist (ondansetron, granisetron, or dolasetron—NOT palonosetron) 1

Note: Palonosetron's 40-hour half-life means it is only given on day 1, unlike other 5-HT3 antagonists 2.

Low Emetogenic Risk Chemotherapy

Choose one of the following:

• Dexamethasone 12 mg PO/IV daily 1
• Metoclopramide 10-40 mg PO/IV every 4-6 hours (monitor for dystonic reactions) 1
• Prochlorperazine 10 mg PO/IV every 4-6 hours (monitor for dystonic reactions) 1
• Optional: Lorazepam 0.5-2 mg every 4-6 hours PRN 1

Minimal Emetogenic Risk Chemotherapy

No routine prophylaxis required 1

Postoperative Nausea and Vomiting (PONV)

Aprepitant 40 mg PO demonstrates superiority over ondansetron 4 mg:

• 84% vs 71.4% no vomiting at 0-24 hours (p<0.001) 5
• 81.5% vs 66.3% no vomiting at 0-48 hours 5
• Aprepitant delayed time to first vomiting compared to ondansetron 5

Alternative: Ondansetron has been shown more effective than placebo, droperidol, or metoclopramide for PONV prophylaxis and treatment 3.

Breakthrough/Rescue Treatment

General principle: Add an agent from a different drug class 1

Options include:

• Prochlorperazine 25 mg suppository PR every 12 hours or 10 mg PO/IV every 4-6 hours 1
• Metoclopramide 10-40 mg PO/IV every 4-6 hours 1
• Ondansetron 16 mg PO or 8 mg IV daily 1
• Granisetron 1-2 mg PO daily or 0.01 mg/kg IV 1
• Haloperidol 1-2 mg PO every 4-6 hours PRN 1
• Olanzapine 2.5-5 mg PO BID (category 2B) 1
• Dexamethasone 12 mg PO/IV daily 1
• Cannabinoids (dronabinol 5-10 mg PO every 3-6 hours or nabilone 1-2 mg PO BID) for refractory cases 1

Critical caveat: Around-the-clock scheduled dosing is strongly preferred over PRN dosing, as prevention is far more effective than treatment of established emesis 1.

Important Safety Considerations

• Dolasetron IV formulation withdrawn due to cardiac safety concerns (QT prolongation); only oral formulation available 2
• Monitor for dystonic reactions with metoclopramide and prochlorperazine; treat with diphenhydramine 25-50 mg PO/IV every 4-6 hours 1
• Ondansetron and other 5-HT3 antagonists can prolong QT interval; use caution in patients with cardiac conduction abnormalities 6, 7
• Aprepitant reduces efficacy of hormonal contraceptives; use backup contraception during treatment and for 1 month after 5
• Warfarin interaction with aprepitant: Monitor INR closely at 7-10 days following each chemotherapy cycle 5

Delayed Emesis Prevention

For high emetogenic chemotherapy: Continue prophylaxis for 2-4 days after chemotherapy completion with dexamethasone and aprepitant 1

For moderate emetogenic chemotherapy: Metoclopramide or ondansetron combined with dexamethasone offers similar protection for delayed emesis, with metoclopramide preferred due to lower cost 8. However, over 40% of patients still experience delayed symptoms despite prophylaxis 4.