Keppra (Levetiracetam) Side Effects
Levetiracetam is generally well-tolerated with the most common side effects being somnolence, asthenia (weakness), dizziness, and behavioral disturbances including irritability and aggression, which occur in approximately 12-15% of patients. 1, 2
Most Common Side Effects
Neurological Effects
- Somnolence (drowsiness) occurs in 12-15% of patients and typically appears during the first 4 weeks of treatment 1
- Dizziness affects 4-9% of patients 1
- Asthenia (weakness/fatigue) is reported in 8-15% of patients 1, 3
- Headache is common but occurs at similar rates to placebo 1, 4
- Ataxia (coordination problems) occurs in 3% of patients 1
Behavioral and Psychiatric Effects
- Irritability, agitation, anger, and aggressive behavior represent the most significant concern, occurring in 12-15% of patients 2
- These behavioral effects are more likely in learning disabled individuals, those with prior psychiatric history, and those with symptomatic generalized epilepsy 2
- Depression occurs in 4-5% of patients 1
- Anxiety and nervousness affect 2-4% of patients 1
- Delirium has been reported, though it is uncommon, and can present with disorientation, agitation, and fluctuating consciousness 5
- Psychosis is a rare but recognized adverse effect 5
Gastrointestinal Effects
- Anorexia occurs in 3% of patients 1
- Nausea is reported in 2-8% of patients 1, 3
- Diarrhea affects 7-8% of patients 1
Other Common Effects
- Infection/nasopharyngitis occurs in 5-14% of patients 1, 3
- Pharyngitis affects 4-7% of patients 1
- Vertigo occurs in 3-5% of patients 1
Serious but Rare Side Effects
Hematologic Effects
- Slight trends toward lower white and red blood cell counts have been detected in studies, though clinically significant myelosuppression is uncommon 2
Cardiovascular Effects
- No significant changes in blood pressure or heart rate have been documented, even with rapid IV loading 6
- No ECG abnormalities were observed in pediatric loading studies 6
Infusion-Related Effects (IV Administration)
- Injection site pain is mild to moderate when it occurs 6, 1
- No local infusion site reactions were reported in rapid IV loading studies 6
Important Clinical Considerations
Time Course
Most adverse effects, particularly somnolence, asthenia, and dizziness, occur predominantly during the first 4 weeks of treatment 1
Discontinuation Rates
In major clinical trials, discontinuation rates due to adverse events were 6.9-10.9% for levetiracetam compared to 5.3-8.6% for placebo 2. In clinical practice, behavioral adverse effects are the most common reason for drug discontinuation 2
Organ Toxicity
No organ toxicity has been described with patient exposures exceeding 500,000, and laboratory parameters are generally not significantly affected 2
Drug Interactions
Levetiracetam has no significant drug-drug interactions because its metabolism is independent of the cytochrome P450 enzyme system 2, 3. This represents a major safety advantage over older antiepileptic drugs 6
Dose-Response Relationship
Adverse effects appear similar across the therapeutic dose range (1000-3000 mg/day), with no clear dose-dependent increase in side effects 4
Withdrawal Effects
No withdrawal-related adverse events or rebound phenomena have been reported after discontinuation or down-titration 4