Levetiracetam Pediatric Adverse Effects
Behavioral problems and somnolence are the most common adverse effects of levetiracetam in pediatric patients, occurring in approximately 11% and 8% of children respectively, with behavioral disturbances being the leading cause of treatment discontinuation. 1, 2
Most Common Adverse Effects in Children
Behavioral and Psychiatric Effects
- Hostility, irritability, and aggression are the most concerning behavioral adverse effects, occurring more frequently in children than adults 1
- Nervousness, agitation, and mood swings affect approximately 10% of pediatric patients 1
- Depression, anxiety, and emotional lability occur in 3-6% of children 1
- Children with pre-existing behavioral problems are at highest risk for behavioral adverse effects 3
- Acute severe aggression requiring medication discontinuation has been reported, though it resolves rapidly after dose reduction or discontinuation 4
Neurological Effects
- Somnolence affects 15% of pediatric patients, typically occurring within the first 4 weeks of treatment 1
- Dizziness occurs in 7% of children 1
- Asthenia (weakness/fatigue) affects 3% of pediatric patients 1
- Ataxia and coordination problems occur in 3% of children 1
Other Common Effects
- Accidental injury (related to somnolence/dizziness) is reported more frequently in pediatric trials 1
- Respiratory infections including rhinitis (13%), pharyngitis (10%), and cough (11%) 1
- Anorexia occurs in 3% of children 1
Risk Factors and Frequency
Polytherapy vs Monotherapy
- Children on polytherapy experience adverse effects at significantly higher rates (64%) compared to monotherapy (22%) 2
- Treatment discontinuation due to adverse effects occurs in 4.5% of children on polytherapy versus only 0.9% on monotherapy 2
- Overall, 47% of children in prospective studies experienced at least one adverse effect 2
Time Course
- Most adverse effects occur within the first 4 weeks of treatment, particularly somnolence, dizziness, and behavioral changes 1
- Behavioral adverse effects can occur acutely following dose increases 4
Management Strategies
Dose Titration
- Slow titration can minimize behavioral adverse effects and reduce seizure exacerbation 3
- Pediatric doses should be 130-140% of adult doses (typically 20-60 mg/kg/day) 3
- When behavioral changes occur after dose increases, return to baseline dosing typically results in rapid symptom resolution 4
Monitoring Requirements
- Close monitoring for behavioral changes is essential, particularly in the first month of therapy 1, 4
- Screen for pre-existing behavioral problems before initiating therapy, as these patients are at higher risk 3
- Monitor for extreme sleepiness, tiredness, and weakness that may impair daily functioning 1
- Assess for mood changes including aggression, agitation, anger, anxiety, depression, and irritability 1
When to Discontinue
- Discontinue immediately if psychotic symptoms develop (hallucinations, delusions, unusual behavior) 1
- Consider discontinuation for severe behavioral problems, particularly aggression or hostility that impairs quality of life 1, 2
- Treatment discontinuation rates range from 15-17% in clinical trials, with behavioral problems being the primary reason 1
Serious but Rare Adverse Effects
Hematologic and Hepatic
- Leukopenia, neutropenia, thrombocytopenia, and pancytopenia with bone marrow suppression have been reported in postmarketing surveillance 1
- Hepatic failure and hepatitis are rare but serious adverse events 1
- Abnormal liver function tests may occur 1
Other Rare Effects
- Pancreatitis has been reported 1
- Alopecia occurs rarely but typically recovers after discontinuation 1
- Seizure exacerbation can occur in some patients, though slow titration reduces this risk 3
Comparative Safety Profile
- Levetiracetam is generally better tolerated than older antiepileptic drugs like phenytoin or valproic acid according to the American Academy of Neurology 5
- In status epilepticus studies, children in the fosphenytoin group required intubation at significantly higher rates (33%) compared to levetiracetam (8%) 6
- No serious adverse effects were attributable to rapid IV infusion at 5 mg/kg per minute in status epilepticus studies 5