What are the signs of Keppra (levetiracetam) supratherapeutic levels?

Signs of Levetiracetam (Keppra) Supratherapeutic Levels

The most common signs of levetiracetam supratherapeutic levels include somnolence, respiratory depression, decreased deep tendon reflexes, ataxia, and behavioral disturbances such as agitation and irritability. These symptoms typically appear in a dose-dependent manner, with more severe manifestations occurring at higher concentrations.

Neurological Signs

• Somnolence/sedation: The most frequent sign, occurring in 15% of patients at therapeutic levels but increasing significantly with supratherapeutic levels 1
• Ataxia and coordination difficulties: Reported in 3.4% of patients at therapeutic levels, worsening with higher concentrations 1
• Dizziness: Common at therapeutic doses (9%) but more pronounced with elevated levels 1
• Decreased deep tendon reflexes: Particularly notable in overdose cases 2
• Respiratory depression: Can be severe enough to require intubation in significant overdoses 2

Behavioral and Psychiatric Signs

• Irritability: More pronounced at higher levels
• Agitation: Can progress from mild to severe with increasing blood levels
• Emotional lability: Mood swings that worsen with higher concentrations
• Hostility: Particularly notable in pediatric patients (11.9% at therapeutic levels) 1
• Depression: Reported in 3-5% of patients, may worsen with supratherapeutic levels 1

Gastrointestinal Signs

• Nausea/vomiting: May be an early sign of toxicity
• Anorexia: Reduced appetite that worsens with increasing levels

Concentration-Related Effects

In a documented case of severe overdose, a patient with a serum concentration of 400 μg/mL (10-40 times the therapeutic range of 10-37 μg/mL) developed:

• Obtundation requiring intubation
• Significant respiratory depression
• Diminished deep tendon reflexes 2

Severity Based on Concentration

• Mild toxicity (slightly above therapeutic range): Increased somnolence, dizziness, fatigue
• Moderate toxicity: Pronounced sedation, ataxia, behavioral changes
• Severe toxicity (>10x therapeutic levels): Respiratory depression, obtundation, potentially requiring ventilatory support 2, 3

Important Considerations

• Levetiracetam has a relatively wide therapeutic index compared to older antiepileptic drugs 4
• Most overdoses result in relatively mild symptoms with good outcomes following supportive care 3
• The elimination half-life of levetiracetam is approximately 5-7 hours, even in overdose scenarios 2
• Recovery is typically rapid with supportive care, even in significant overdoses 2

Clinical Approach to Suspected Toxicity

1. Assess vital signs: Particularly respiratory status
2. Neurological examination: Focus on level of consciousness, coordination, and reflexes
3. Obtain serum levetiracetam level: Therapeutic range is 10-37 μg/mL
4. Supportive care: The mainstay of treatment for supratherapeutic levels
5. Consider dose reduction: If symptoms are mild and patient is on chronic therapy

Pitfalls to Avoid

• Don't confuse behavioral symptoms with primary psychiatric disorders; these can be direct effects of supratherapeutic levetiracetam levels
• Avoid assuming that all seizures in a patient with elevated levetiracetam levels represent treatment failure; they may indicate toxicity
• Remember that levetiracetam has minimal drug interactions, so toxicity is rarely due to pharmacokinetic interactions with other medications 4

Levetiracetam toxicity typically resolves quickly with supportive care and drug discontinuation or dose reduction, given its relatively short half-life and lack of active metabolites.