What are the side effects of Keppra (levetiracetam)?

Side Effects of Keppra (Levetiracetam)

Levetiracetam is generally well-tolerated with most adverse effects being mild to moderate, primarily consisting of somnolence, asthenia, dizziness, and behavioral changes, with the American Heart Association recommending it over phenytoin or valproic acid due to its superior tolerability profile. 1

Most Common Side Effects

The FDA-approved labeling identifies the following adverse events occurring in at least 1% of patients and more frequently than placebo: 2

Neurological Effects

• Somnolence (15.8%) - the most frequently reported adverse effect 2
• Dizziness (9.4%) 2
• Asthenia/fatigue (14.7%) 2
• Ataxia (3.1%) 2
• Headache - common but occurred at similar rates to placebo 2

Psychiatric and Behavioral Effects

• Depression (4.2%) 2
• Nervousness (4.2%) 2
• Hostility (2.1%) 2
• Irritability - particularly notable in pediatric patients 2
• Emotional lability (2.0%) 2
• Anxiety (2.1%) 2

Behavioral side effects warrant special attention, as they may be more common in patients with prior psychiatric history or neurobehavioral problems. 3

Gastrointestinal Effects

• Anorexia (3.2%) 2
• Nausea - occurred at similar rates to placebo 2
• Diarrhea 2

Respiratory Effects

• Pharyngitis (6.4%) 2
• Rhinitis (4.3%) 2
• Nasopharyngitis - particularly in patients with primary generalized tonic-clonic seizures 2

Time Course and Severity

• Most adverse events appear within the first 4 weeks of treatment, particularly asthenia, somnolence, and dizziness 2
• Adverse effects are generally not dose-dependent and are mostly mild to moderate in intensity 4
• Events typically resolve without medication withdrawal and are transient when the medication is stopped 4

Special Population Considerations

Pediatric Patients

• Behavioral adverse events are increased in children, with personality disorder (8.7%), nervousness (10.2%), and emotional lability (6.4%) occurring more frequently than in adults 2
• Children with prior behavioral problems may experience more pronounced psychiatric side effects 4

Rapid IV Administration

• When administered as rapid IV push (5 mg/kg per minute), no serious adverse effects were attributable to the infusion rate 1
• Hypotension occurs in only 1.7-3.2% of cases and bradycardia in 3.5-7.8% 5
• In oral loading studies, 89% of patients reported no adverse effects, with only 11% experiencing transient irritability, imbalance, tiredness, or lightheadedness 5, 1

Rare but Important Adverse Effects

Renal Effects

• Dose adjustments are necessary in patients with renal dysfunction due to predominant renal elimination 1
• Rare case reports suggest levetiracetam may contribute to acute kidney injury, though this is uncommon 6
• Renal function should be monitored during treatment 6

Other Rare Effects

• Hypersensitivity reactions are rare 4
• No idiosyncratic events have been reported 4
• No significant changes in hematology, chemistry profiles, or weight occur 4

Comparative Safety Profile

The American Academy of Neurology notes that phenytoin causes poorer cognitive outcomes and excess morbidity, prompting the use of levetiracetam as a preferred alternative. 1 This positions levetiracetam as having a superior safety profile compared to older antiepileptic drugs like phenytoin or valproic acid 1.

Clinical Monitoring Recommendations

• Monitor for behavioral changes, particularly in the first month of therapy 2
• Assess renal function, especially in patients with pre-existing renal impairment 1
• Watch for respiratory compromise when combining with other sedatives, particularly in neonates 7
• No routine laboratory monitoring of drug levels or hepatic function is required due to minimal hepatic metabolism 4