What are the first-line and second-line treatments for nausea and vomiting, specifically using antiemetic (anti-emetic) medications?

Antiemetic Treatment: First-Line and Second-Line Therapy

For chemotherapy-induced nausea and vomiting, first-line prophylaxis consists of a 5-HT3 receptor antagonist (preferably palonosetron) combined with dexamethasone, with aprepitant added for highly emetogenic regimens; second-line therapy for breakthrough or refractory symptoms involves adding dopamine antagonists (metoclopramide or prochlorperazine) to the existing regimen. 1

First-Line Antiemetic Therapy by Emetogenic Risk

Highly Emetogenic Chemotherapy (Grade 4)

• Administer all three agents together: 1, 2

  • 5-HT3 antagonist (palonosetron preferred): 0.25 mg IV once on day 1 1
  • Dexamethasone: 20 mg PO/IV on day 1 (reduce to 10 mg if combined with aprepitant) 1, 2
  • Aprepitant: 125 mg PO day 1, then 80 mg PO days 2-3 1, 3
  • Optional lorazepam: 1 mg PO every 1-2 hours as needed 1, 2

• Timing: Give prophylactically 30-60 minutes before chemotherapy starts 1, 2

• Palonosetron is superior to other 5-HT3 antagonists for both acute and delayed nausea/vomiting in highly emetogenic settings, based on meta-analysis data 1

Moderately Emetogenic Chemotherapy (Grade 3)

• Standard regimen: 1, 2
  • 5-HT3 antagonist (palonosetron preferred): 0.25 mg IV or ondansetron 16-24 mg PO once 1, 2
  • Dexamethasone: 20 mg PO/IV on day 1 1
  • Add aprepitant for select moderate-risk agents (carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, irinotecan): 125 mg day 1, then 80 mg days 2-3 1

Low Emetogenic Chemotherapy (Grade 1-2)

• Single agent options: 1, 2
  • Dexamethasone 20 mg PO (optional) 1
  • OR Prochlorperazine 10 mg PO before treatment, then every 6 hours PRN 1
  • OR Metoclopramide 20-30 mg PO 3-4 times daily 1

Delayed Emesis Prevention (Days 2-5)

After Highly Emetogenic Chemotherapy

• Continue aprepitant: 80 mg PO daily on days 2-3 1, 3
• Dexamethasone: 4-8 mg PO twice daily for 2-4 days 1, 2
• Do NOT continue 5-HT3 antagonists beyond day 1 for highly emetogenic regimens 1

After Moderately Emetogenic Chemotherapy

• Optional dexamethasone: 4 mg PO twice daily for 2 days 1, 2
• 5-HT3 antagonists may be used as one option for delayed emesis in moderate-risk settings 1

Second-Line Therapy for Breakthrough/Refractory Nausea and Vomiting

When first-line prophylaxis fails, add dopamine antagonists to the existing 5-HT3 antagonist and corticosteroid regimen. 1

Dopamine Antagonist Options (Given 3-4 Times Daily)

• Metoclopramide: 20-30 mg PO/IV 1
• Prochlorperazine: 10-20 mg PO/IV 1
• Haloperidol: 1 mg PO every 4 hours PRN 1

Additional Second-Line Agents

• Lorazepam: 1-2 mg PO/IV for anticipatory nausea or anxiety-related symptoms 1
• Dronabinol: 2.5-7.5 mg PO every 4 hours PRN for rescue/refractory use (per American Society of Clinical Oncology recommendation over medical marijuana) 4
• Promethazine: 25-50 mg PR every 6 hours PRN 1

Route Considerations for Active Vomiting

• Switch to IV administration if patient has active nausea/vomiting and cannot tolerate oral medications 1, 2
• Ondansetron IV: 8 mg bolus, may use 1 mg/hour continuous infusion for severe cases 2

Critical Pitfalls and Caveats

Common Errors to Avoid

• Never use ondansetron alone for highly emetogenic chemotherapy—combination with dexamethasone and aprepitant is mandatory 1, 5
• Failure to control acute emesis predicts delayed emesis—aggressive prophylaxis on day 1 is essential 5
• Monitor for dystonic reactions with dopamine antagonists (metoclopramide, prochlorperazine); treat with diphenhydramine or benztropine 1, 6
• QT prolongation risk with 5-HT3 antagonists and metoclopramide—use caution in patients with cardiac conduction abnormalities 7, 6

Dose Adjustments

• Reduce dexamethasone to 50% when combining with aprepitant due to CYP3A4 interactions 1
• Ondansetron requires dose adjustment in hepatic impairment 7

Anticipatory Nausea and Vomiting

• Prevention is key—optimal antiemetic therapy during every cycle prevents anticipatory symptoms 1
• If it develops: Lorazepam 1 mg PO at bedtime before chemotherapy and morning of treatment 1
• Behavioral techniques (hypnosis, guided imagery) may be helpful adjuncts 1

Equivalency Within Drug Classes

• All 5-HT3 antagonists have comparable efficacy when dosed appropriately (ondansetron, granisetron, tropisetron, dolasetron), except palonosetron shows superior delayed emesis control 1, 8
• Oral route is preferred for routine prophylaxis unless patient has active symptoms 1