Can Zofran (Ondansetron) Cause Drowsiness?
Ondansetron can cause sedation, but it is not a common side effect and occurs at a much lower rate than with many other antiemetic agents.
Evidence from FDA Drug Labeling
The FDA-approved prescribing information for ondansetron does not list drowsiness or sedation as a common adverse reaction in the primary safety tables for chemotherapy-induced or postoperative nausea and vomiting 1. The most frequently reported adverse reactions (≥5%) in adults receiving ondansetron tablets include:
- Headache (24% vs 13% placebo) 1
- Malaise/fatigue (13% vs 2% placebo) 1
- Constipation (9% vs <1% placebo) 1
- Dizziness (7% vs 6% placebo) 1
Notably, while fatigue is reported at 13%, this is distinct from sedation or drowsiness 1.
Clinical Research Evidence
Multiple clinical pharmacology studies confirm that sedation is an uncommon side effect of ondansetron:
- Sedation occurs but is infrequent: Research indicates that sedation can occur with ondansetron but is reported as a minor adverse effect, with headache and constipation being the most common side effects 2, 3
- Well-tolerated profile: Ondansetron is generally well tolerated with few adverse events, and sedation when it occurs is typically mild 3, 4
- No untoward side effects in some studies: In a study of 40 patients receiving ondansetron lingual tablets, no adverse side effects including sedation were registered 5
Comparison to Other Antiemetics
The sedation profile of ondansetron is markedly better than alternative antiemetic agents:
- Olanzapine causes significant drowsiness: Common side effects with olanzapine include fatigue, drowsiness, and sleep disturbances, and it should be used with caution in elderly patients 6
- Metoclopramide has comparable efficacy but different side effect profile: While ondansetron demonstrates equal or superior efficacy to high-dose metoclopramide, it is not associated with extrapyramidal reactions that can occur with metoclopramide 2
Clinical Implications
When counseling patients about ondansetron:
- Inform patients that drowsiness is possible but uncommon: While sedation can occur, it is not among the most frequent adverse effects 1, 2, 3
- Headache and constipation are more likely: Patients should be counseled that headache (24%) and constipation (9%) are the most common side effects they may experience 1
- Fatigue differs from sedation: The 13% incidence of malaise/fatigue should not be conflated with drowsiness or sedation 1
- Monitor for dizziness: Dizziness occurs in approximately 7% of patients, which may be confused with drowsiness by some patients 1
Special Populations
In pregnancy, ondansetron is recommended as a second-line therapy for hyperemesis gravidarum, with no specific mention of sedation as a limiting factor, though it should only be administered after 10 weeks of pregnancy due to potential cardiac concerns 6.