What antiemetics can be used for the management of nausea and vomiting?

Antiemetics for Management of Nausea and Vomiting

Primary Antiemetic Classes

The main antiemetic drug classes available include 5-HT3 receptor antagonists, NK1 receptor antagonists, dopamine receptor antagonists, corticosteroids, antihistamines, anticholinergics, benzodiazepines, and cannabinoids. 1

5-HT3 Receptor Antagonists (Serotonin Antagonists)

• Ondansetron 4-8 mg PO/IV 2-3 times daily 2, 3
• Granisetron 1 mg PO twice daily or 34.3 mg transdermal patch weekly 2
• Palonosetron (IV formulation only) 1
• Tropisetron 5 mg IV 1
• Dolasetron 100 mg IV 1

These agents are typically given once daily, with oral administration preferred for routine use 1. Substances within this class demonstrate comparable efficacy 1.

NK1 Receptor Antagonists

• Aprepitant 125 mg on Day 1, then 80 mg on Days 2-3 (for chemotherapy-induced nausea/vomiting) 4
• Aprepitant 40 mg within 3 hours prior to anesthesia induction (for postoperative nausea/vomiting) 4
• Fosaprepitant (IV formulation) 1
• Netupitant (typically combined with palonosetron) 5
• Rolapitant 5

Critical drug interaction: When combining aprepitant with corticosteroids, reduce corticosteroid doses to 50% (oral) or 75% (IV) due to CYP3A4 metabolism 1, 4.

Dopamine Receptor Antagonists

• Metoclopramide 5-10 mg PO/IV three times daily 2, 6
• Haloperidol 0.5-2 mg PO/IV every 4-6 hours 2
• Prochlorperazine 6

Metoclopramide carries a black box warning for tardive dyskinesia, though actual risk may be lower than previously estimated 6. Monitor for extrapyramidal side effects with all dopamine antagonists 2, 6.

Corticosteroids

• Dexamethasone 20 mg IV single dose for cisplatin-induced emesis; 8 mg IV for cyclophosphamide/anthracycline-based chemotherapy 1
• For delayed emesis, corticosteroids are administered twice daily 1

Additional Agents

• Olanzapine 2.5-5 mg PO daily, particularly effective in palliative care and refractory symptoms 2, 6
• Benzodiazepines (e.g., lorazepam 0.5-1 mg PO/IV every 4-6 hours) for anxiety-related nausea 2, 6
• Cannabinoids for refractory symptoms, though use caution in elderly patients 2

Treatment Algorithm by Clinical Context

For Low/Minimal Emetogenic Chemotherapy

Use single-agent therapy: dexamethasone, a 5-HT3 receptor antagonist, or a dopamine receptor antagonist 1. No prophylactic treatment is needed for delayed emesis in this setting 1.

For Highly Emetogenic Chemotherapy

Combination therapy is essential: NK1 receptor antagonist + 5-HT3 receptor antagonist + corticosteroid 1, 5. The most effective combinations based on network meta-analysis include fosnetupitant + palonosetron, aprepitant + palonosetron, and netupitant + palonosetron 5.

For Moderately Emetogenic Chemotherapy

Either 5-HT3 antagonist + corticosteroid OR add NK1 antagonist for higher-risk patients 1, 5. Rolapitant + granisetron demonstrates high-certainty evidence for superior efficacy compared to granisetron alone 5.

For Postoperative Nausea/Vomiting

Ondansetron 4 mg IV is FDA-approved and effective 3. In pediatric patients aged 1 month and older, ondansetron 0.1 mg/kg IV (maximum 4 mg) prevents vomiting in 89% of patients versus 72% with placebo 3.

For General/Palliative Care Setting

Start with dopamine receptor antagonists (metoclopramide or haloperidol) as first-line 1, 2. If symptoms persist, add 5-HT3 receptor antagonists 2. For refractory symptoms, consider adding olanzapine or switching to combination therapy 2, 6.

Critical Prescribing Considerations

Drug Interactions

• Aprepitant is a CYP3A4 substrate, inhibitor, and inducer 4. Reduce corticosteroid doses by 50-75% when co-administering 1, 4.
• Avoid concurrent use of aprepitant with pimozide (contraindicated) 4.
• Monitor INR closely for 7-10 days when initiating aprepitant in patients on warfarin 4.

Special Populations

In elderly patients, use lower starting doses and monitor for extrapyramidal side effects 2. Avoid long-term benzodiazepine use due to dependence risk 2, 6.

Refractory Symptoms

For breakthrough emesis, add agents from different drug classes rather than switching within the same class 1, 6. Consider continuous IV or subcutaneous infusion of antiemetics, combination therapy targeting multiple receptor sites, or olanzapine for multiply refractory cases 2, 6.

Contraindications

Do not use antiemetics in suspected mechanical bowel obstruction 6. In this setting, consider surgical intervention, stenting, decompression, or octreotide instead 1.

Common Pitfalls

• Waiting for emesis to occur before treating: Antiemetics are most effective when used prophylactically 1.
• Using suboptimal first-line therapy: Maximize antiemetic efficacy upfront rather than reserving more effective agents for later cycles 1.
• Ignoring the choice of 5-HT3 antagonist: Evidence suggests palonosetron may offer superior efficacy compared to older 5-HT3 antagonists, particularly for delayed emesis 5.
• Forgetting corticosteroid dose adjustment: Always reduce corticosteroid doses by 50-75% when combining with aprepitant 1, 4.