What are the long‑term adverse effects of levetiracetam (Keppra) in a 2½‑year‑old girl receiving 3 mL daily (1.5 mL twice daily)?

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Long-Term Concerns with Levetiracetam in a 2.5-Year-Old Girl

The primary long-term concern with levetiracetam (Keppra) in young children is behavioral adverse effects, including irritability, aggression, and mood changes, which occur more commonly in patients with pre-existing psychiatric or neurobehavioral problems. 1, 2

Behavioral and Psychiatric Effects

  • Behavioral side effects are the most serious concern with levetiracetam use and include hostility progressing to aggressive behavior, irritability, and mood disturbances. 3, 1
  • These behavioral effects may be more pronounced in children and can manifest as increased irritability, emotional lability, or aggressive outbursts. 1
  • In pediatric studies, behavioral adverse effects led to discontinuation in approximately 12% of children receiving high doses. 4
  • Parents should monitor for personality changes, increased tantrums beyond normal developmental behavior, sleep disturbances, or unusual aggression. 1, 2

Cognitive and Developmental Considerations

  • Levetiracetam does not cause cognitive impairment, which distinguishes it favorably from older antiepileptic drugs like phenytoin. 5, 2
  • The drug is not associated with drug-induced weight gain, another advantage over many alternative antiepileptic medications. 2
  • Long-term cognitive development appears preserved, though ongoing monitoring of developmental milestones remains important in any child on chronic antiepileptic therapy. 2

Common Transient Side Effects

  • Drowsiness and ataxia are the most frequently reported acute effects in young children, particularly in those who are levetiracetam-naive. 6
  • These effects are typically mild to moderate and transient, resolving with continued therapy or dose adjustment. 3, 6
  • In a large pediatric ingestion study, 80.5% of children experienced no adverse effects, with only 18.3% having minor outcomes and 1.2% moderate outcomes. 6

Favorable Safety Profile

  • No serious idiosyncratic side effects (such as severe rashes, hepatotoxicity, or bone marrow suppression) have been reported with levetiracetam, unlike many other antiepileptic drugs. 3
  • The drug has no clinically relevant drug-drug interactions due to minimal hepatic metabolism through cytochrome P450 pathways. 3, 2
  • Levetiracetam is generally well-tolerated in the pediatric population, with children tolerating doses up to 275 mg/kg/day in specialized cases without serious adverse effects. 4

Monitoring Recommendations

  • Watch specifically for behavioral changes: increased irritability, aggression, mood swings, or personality alterations that differ from normal toddler behavior. 1
  • Monitor for transient drowsiness or unsteadiness, particularly during dose adjustments. 6
  • Ensure regular developmental assessments to confirm age-appropriate cognitive and motor milestone achievement. 2
  • Consider dose adjustment or medication change if significant behavioral problems emerge, as these are the primary reason for discontinuation. 4, 1

Critical Caveat

The 3 mL daily dose (1.5 mL BID) requires verification of the concentration of the oral solution being used, as levetiracetam oral solution typically comes in 100 mg/mL concentration, which would provide 300 mg/day total—a reasonable maintenance dose for a 2.5-year-old child weighing approximately 12-15 kg. 7

References

Research

Levetiracetam for managing neurologic and psychiatric disorders.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2009

Research

Levetiracetam.

Drugs of today (Barcelona, Spain : 1998), 2007

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Levetiracetam Dosing for Seizure Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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