Can Emeset (Ondansetron) cause Extrapyramidal Symptoms (EPS)?

Can Ondansetron (Emeset) Cause Extrapyramidal Symptoms (EPS)?

Yes, ondansetron (Emeset) can cause extrapyramidal symptoms (EPS), though this is a rare adverse effect documented in the FDA drug label and case reports. 1, 2, 3

Mechanism and Risk

• Ondansetron is a selective 5-HT3 receptor antagonist with low affinity for dopamine receptors, which explains why EPS are uncommon compared to traditional antiemetics like metoclopramide 2
• EPS are specifically listed as a "less common adverse reaction" in the FDA drug label for ondansetron, occurring in less than 1% of patients 1
• The mechanism is thought to involve an imbalance between inhibitory and excitatory neurotransmitters in the extrapyramidal system 2

Types of EPS Reported with Ondansetron

• Dystonic reactions, including:
  • Oromandibular dystonia 3
  • Oculogyric crisis (abnormal eye movements) 2, 3
  • Limb dystonia 3
• Multifocal encephalopathy with extrapyramidal features 3

Risk Factors

• Previous history of drug-induced dystonic reactions may increase susceptibility 4
• Concomitant use of other medications that can cause EPS may have synergistic effects 5
• Pediatric patients may be at higher risk for medication side effects including EPS 6

Clinical Significance

• While rare, ondansetron-induced EPS can be severe and may require:
  • Specific treatment with anticholinergics, antihistamines, or benzodiazepines 2
  • In severe cases, respiratory support including intubation may be necessary 2
• These reactions can occur even in patients who have previously received ondansetron without complications 2

Comparison to Other Antiemetics

• Ondansetron has a significantly lower risk of EPS compared to traditional antiemetics like metoclopramide 7
• Metoclopramide and phenothiazines have much higher rates of drug-induced extrapyramidal adverse effects 6
• When EPS occur with ondansetron, they are often unpredictable and can be dramatic in presentation 3

Management of Ondansetron-Induced EPS

• Immediate discontinuation of ondansetron 2
• Treatment options include:
  • Anticholinergic medications (e.g., benztropine) 2
  • Antihistamines (e.g., diphenhydramine) 2
  • Benzodiazepines 2
• Supportive care as needed, including respiratory support in severe cases 2

Clinical Implications

• Healthcare providers should be aware of this rare but potentially serious adverse effect 3
• Consider alternative antiemetics in patients with a history of drug-induced movement disorders 4
• Monitor patients closely after ondansetron administration, particularly those with risk factors 8
• Document any EPS reactions to avoid re-exposure in susceptible individuals 2