What are the first-line and second-line treatments for nausea and vomiting using antiemetics such as ondansetron (5-HT3 receptor antagonist) and metoclopramide?

First-Line and Second-Line Antiemetic Treatment

For chemotherapy-induced nausea and vomiting, use ondansetron 8 mg IV or oral (5-HT3 antagonist) plus dexamethasone 20 mg as first-line prophylaxis, with metoclopramide 20-30 mg oral 3-4 times daily reserved as second-line or breakthrough therapy for refractory cases. 1, 2

First-Line Treatment Strategy

High Emetogenic Risk Chemotherapy

• Ondansetron 8 mg IV or oral (or equivalent 5-HT3 antagonist: granisetron 1-2 mg) given 30-60 minutes before chemotherapy 1, 2
• Dexamethasone 20 mg oral or IV on day 1 before chemotherapy 1
• Continue dexamethasone 4-8 mg oral twice daily for 2-4 days post-chemotherapy for delayed emesis 1
• Note: 5-HT3 antagonists are given once daily on day 1 only for prophylaxis 1

Moderate Emetogenic Risk Chemotherapy

• Ondansetron 16 mg oral or 8 mg IV before chemotherapy 1
• Dexamethasone 20 mg oral or IV pretreatment 1
• Optional dexamethasone 4 mg oral twice daily for 2 days post-chemotherapy 1

Low Emetogenic Risk Chemotherapy

• Dexamethasone 20 mg oral (optional) 1
• Prochlorperazine 10 mg oral pretreatment (optional) 1
• Prochlorperazine 10 mg oral every 6 hours as needed 1

Second-Line/Breakthrough Treatment

When First-Line Fails

Add dopamine antagonists to the existing 5-HT3 antagonist and corticosteroid regimen 1:

• Metoclopramide 20-30 mg oral 3-4 times daily 1
• Alternative: Prochlorperazine 10-20 mg oral 3-4 times daily 1
• Monitor for dystonic reactions with dopamine antagonists; treat with diphenhydramine if they occur 1

Rescue Therapy Dosing

• Metoclopramide 5-20 mg oral or IV, titrate up to maximum 16 mg daily as needed 1
• Administer 3-4 times daily for breakthrough symptoms 1

Important Clinical Considerations

Ondansetron Specifics

• Standard IV dose: 8 mg or 0.15 mg/kg 1, 2
• Standard oral dose: 8-24 mg depending on emetogenic risk 1
• Oral dissolving tablets and soluble films available at 8 mg 1, 2
• All 5-HT3 antagonists within the class have comparable efficacy 1

Metoclopramide Specifics

• Dosing: 20-30 mg oral, given 3-4 times daily 1
• Used as second-line when added to 5-HT3 antagonists and corticosteroids for refractory cases 1
• Critical caveat: Monitor closely for extrapyramidal symptoms and dystonic reactions 1

Route of Administration

• Oral route recommended for routine prophylactic use 1
• IV route indicated when patient has active nausea/vomiting and cannot tolerate oral medications 1
• Antiemetics should be given prophylactically 30-60 minutes before chemotherapy initiation 1

Hepatic Impairment

• Do not exceed 8 mg total daily dose of ondansetron in patients with severe hepatic impairment 2

Common Pitfalls to Avoid

• Do not continue 5-HT3 antagonists beyond day 1 for delayed emesis prophylaxis in standard regimens 1
• Do not use metoclopramide as monotherapy for high or moderate emetogenic chemotherapy—it is inferior to 5-HT3 antagonists 1
• Avoid assuming class effect for side effects—ondansetron has greater CNS side effects than other 5-HT3 antagonists, while dolasetron has cardiovascular concerns 3

Postoperative Nausea and Vomiting

• Ondansetron 4 mg IV is the optimal dose for treatment of established postoperative nausea and vomiting 4
• Effective for 24-hour control with single dose administration 4

Radiation-Induced Nausea and Vomiting

• High-risk (total body irradiation): Ondansetron 8 mg oral/IV plus dexamethasone 4 mg oral/IV once daily before radiation 1
• Moderate-risk (upper abdomen): Same regimen as high-risk 1
• Low-risk (brain, head/neck, thorax, pelvis): Ondansetron 8 mg oral/IV; add metoclopramide 5-20 mg oral/IV as rescue therapy 1