What are the first-line treatments for nausea and vomiting, including the use of antiemetics such as 5-HT3 (5-hydroxytryptamine 3) receptor antagonists like ondansetron (Zofran)?

First-Line Antiemetic Treatments for Nausea and Vomiting

For chemotherapy-induced nausea and vomiting, use 5-HT3 receptor antagonists (such as ondansetron 8 mg oral or IV) combined with dexamethasone as first-line prophylaxis, administered 30-60 minutes before chemotherapy begins. 1, 2

Chemotherapy-Induced Nausea and Vomiting (CINV)

High Emetogenic Risk Chemotherapy

The optimal regimen combines three drug classes:

• 5-HT3 antagonist (ondansetron 8 mg oral/IV, granisetron 2 mg oral or 1 mg IV, or palonosetron 0.25 mg IV) given once daily before chemotherapy 1
• Corticosteroid (dexamethasone 12 mg IV/oral on day 1, then reduced doses on days 2-3) 1
• NK1 antagonist (aprepitant 125 mg oral on day 1, then 80 mg on days 2-3) for maximal protection 1

Palonosetron is the preferred 5-HT3 antagonist for high emetogenic chemotherapy based on meta-analyses showing superior control of both acute and delayed nausea/vomiting compared to other 5-HT3 antagonists, though it costs significantly more ($188.70 vs $0.68-$2.08 for generic alternatives). 1

Moderate Emetogenic Risk Chemotherapy

Use a two-drug combination:

• 5-HT3 antagonist (any agent acceptable, but palonosetron preferred based on superior delayed emesis control) 1
• Dexamethasone 8 mg IV/oral on day 1 1
• Add aprepitant (125 mg day 1,80 mg days 2-3) for select moderate-risk agents including carboplatin, cisplatin, doxorubicin, epirubicin, ifosfamide, and irinotecan 1

Important dosing note: When combining aprepitant with dexamethasone, reduce the corticosteroid dose by 50% due to CYP3A4 interactions. 1

Low Emetogenic Risk Chemotherapy

Single-agent prophylaxis is sufficient:

• Dexamethasone 4-8 mg oral/IV, OR 1
• Dopamine antagonist (metoclopramide 20 mg oral or prochlorperazine 10 mg oral/IV) 1

Minimal Emetogenic Risk

Use rescue therapy only with either a dopamine antagonist or 5-HT3 antagonist as breakthrough treatment. 1

Radiation-Induced Nausea and Vomiting (RINV)

High Risk (Total Body Irradiation)

• 5-HT3 antagonist (ondansetron 8 mg oral/IV or granisetron 2 mg oral/1 mg IV) before each fraction, continuing for 24 hours after completion 1
• Dexamethasone 4 mg oral/IV for the first 5 fractions 1

Moderate Risk (Upper Abdomen, Craniospinal)

• 5-HT3 antagonist before each fraction throughout radiotherapy 1
• Dexamethasone 4 mg oral/IV during fractions 1-5 (adding dexamethasone provides superior vomiting protection and lower nausea) 1

Low Risk (Brain, Head/Neck, Thorax, Pelvis)

• 5-HT3 antagonist as prophylaxis or rescue therapy 1
• Dopamine antagonist (metoclopramide 20 mg oral or prochlorperazine 10 mg oral/IV) as alternative 1

Postoperative Nausea and Vomiting (PONV)

Ondansetron 4 mg IV is FDA-approved and effective for PONV prevention, though specific dosing varies by patient age and weight. 2, 3

Key Administration Principles

Timing and Route

• Administer prophylactically 30-60 minutes before the emetogenic stimulus (chemotherapy, radiation, or surgery) 1
• Oral and IV formulations are equally effective when dosed appropriately; use oral for convenience and cost savings unless the patient is actively vomiting 1
• If breakthrough nausea/vomiting occurs, switch to IV administration 1

Dosing Frequency

• 5-HT3 antagonists and corticosteroids: once daily (except corticosteroids are given twice daily for delayed emesis) 1
• Dopamine antagonists: 3-4 times daily 1
• All agents within the same class have comparable efficacy at appropriate doses 1

Critical Warnings and Contraindications

Serotonin Syndrome Risk

Absolutely avoid all 5-HT3 antagonists (ondansetron, granisetron, palonosetron, dolasetron, tropisetron) in patients with serotonin syndrome. 4, 2

Safe alternatives for serotonin syndrome:

• Dopamine antagonists (metoclopramide 10-20 mg PO/IV 3-4 times daily, prochlorperazine 10-20 mg PO or 5-10 mg IV 3-4 times daily, or haloperidol 0.5-2 mg IV/PO every 6-8 hours) 4
• Dexamethasone 2-8 mg IV/PO as adjunctive therapy 4
• Lorazepam 0.5-2 mg PO/IV every 4-6 hours for anticipatory nausea 4

QT Prolongation

Ondansetron causes dose-dependent QT prolongation and cases of Torsade de Pointes. Avoid in patients with congenital long QT syndrome and monitor ECGs in patients with electrolyte abnormalities, cardiac failure, arrhythmias, or concurrent QT-prolonging drugs. 2, 3

Immunotherapy Considerations

Exercise caution with corticosteroids when combining chemotherapy with checkpoint inhibitors (pembrolizumab, atezolizumab, ipilimumab), as systematic corticosteroids may attenuate immunotherapy benefit. Consider using 5-HT3 antagonists alone or with reduced corticosteroid doses. 1

Hepatic Impairment

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

Common Pitfalls to Avoid

• Failing to provide delayed emesis prophylaxis: Continue antiemetics for days 2-7 after chemotherapy, not just day 1 1
• Underdosing corticosteroids: Use evidence-based doses (dexamethasone 20 mg IV for cisplatin, 8 mg IV for anthracycline/cyclophosphamide) 1
• Using 5-HT3 antagonists alone for high-risk chemotherapy: Always combine with dexamethasone and aprepitant for maximal protection 1
• Monitoring for dystonic reactions: When using dopamine antagonists (metoclopramide, prochlorperazine), have diphenhydramine available for treatment 1
• Masking ileus: In post-abdominal surgery or chemotherapy patients, monitor for decreased bowel activity as antiemetics may mask progressive ileus or gastric distention 2, 3