What anti‑emetic alternatives to ondansetron can be used for a healthy adult with vomiting due to acute gastroenteritis when ondansetron is unavailable, contraindicated, or not tolerated?

Antiemetic Alternatives to Ondansetron for Vomiting in Adults

Metoclopramide and prochlorperazine are the most evidence-based alternatives to ondansetron for treating vomiting in adults with acute gastroenteritis, with metoclopramide preferred as first-line due to its comparable efficacy and more favorable safety profile. 1

First-Line Alternative: Metoclopramide

• Metoclopramide 10 mg IV/IM is an effective first-line alternative when ondansetron is unavailable or contraindicated, demonstrating comparable antiemetic efficacy in emergency department settings 1
• The primary limitation is akathisia (restlessness), which can develop at any time within 48 hours post-administration and requires monitoring 1
• Slowing the infusion rate significantly reduces akathisia incidence, and if it occurs, treat immediately with IV diphenhydramine 25-50 mg 1
• Metoclopramide should be avoided in patients with gastrointestinal obstruction, perforation, or hemorrhage 1

Second-Line Alternative: Prochlorperazine

• Prochlorperazine 10 mg IV/IM is effective but carries higher risk of extrapyramidal side effects compared to metoclopramide 1
• Like metoclopramide, akathisia is a significant concern requiring monitoring for 48 hours and potential treatment with diphenhydramine 1
• Use with extreme caution in elderly patients due to increased sensitivity to anticholinergic effects (urinary retention, confusion) and neuromuscular reactions (parkinsonism, tardive dyskinesia) 2
• Prochlorperazine should be avoided in patients with glaucoma due to anticholinergic effects 2

Third-Line Options with Significant Limitations

Promethazine

• Promethazine 12.5-25 mg IV/IM/PO may be considered when sedation is desirable, but it is more sedating than other alternatives 1
• Critical safety concern: promethazine has potential for severe vascular damage with IV administration and should be given deep IM when possible 1
• Promethazine is contraindicated in children under 2 years due to respiratory depression risk 3
• Dosing for adults: 25 mg every 4-6 hours as needed for nausea/vomiting 3

Dimenhydrinate

• Dimenhydrinate 50 mg IV/IM every 4 hours is an option, though primarily indicated for motion sickness rather than gastroenteritis 4
• For IV administration, each 50 mg must be diluted in 10 mL of 0.9% sodium chloride and injected over 2 minutes to prevent adverse reactions 4
• Less evidence supports its use specifically for gastroenteritis-related vomiting compared to other agents 5

Critical Clinical Algorithm

1. First, attempt proper oral rehydration with small, frequent volumes (5-10 mL every 1-2 minutes) before any antiemetic, as this successfully rehydrates >90% of patients 6

2. If vomiting interferes with oral rehydration:

   • First choice: Metoclopramide 10 mg IV (slow infusion) or IM
   • Second choice: Prochlorperazine 10 mg IV (slow infusion) or IM
   • Third choice: Promethazine 25 mg IM (avoid IV if possible)

3. Monitor all patients for akathisia for 48 hours after metoclopramide or prochlorperazine administration 1

4. Have diphenhydramine 25-50 mg IV readily available to treat extrapyramidal symptoms if they develop 1

Important Contraindications and Pitfalls

• Never use antiemetics in patients with bloody diarrhea, fever with diarrhea, or suspected inflammatory/bacterial gastroenteritis 6
• Avoid all phenothiazines (promethazine, prochlorperazine) in patients with suspected CNS infections, dehydration, or acute febrile illness as they dramatically increase risk of neuromuscular reactions 2
• Do not use antiemetics as a substitute for proper fluid and electrolyte therapy—they are adjunctive only 6
• In elderly patients, start at the lowest effective dose due to increased sensitivity to anticholinergic and extrapyramidal effects 2
• Assess for QT-prolonging medications before using any antiemetic, as drug interactions can precipitate dangerous arrhythmias 6
• Droperidol, while effective, should be reserved only for refractory cases due to FDA black box warning regarding QT prolongation 1