What are the contraindications to Keppra (levetiracetam) administration?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: August 6, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Contraindications to Keppra (Levetiracetam) Administration

The only absolute contraindication to Keppra (levetiracetam) administration is a history of hypersensitivity to levetiracetam or any of its inactive ingredients. 1

Relative Contraindications and Special Considerations

1. Hypersensitivity Reactions

  • Previous allergic reaction to levetiracetam or any component of the formulation
  • Manifestations may include rash, urticaria, or more severe reactions

2. Renal Impairment

  • Not a contraindication but requires dose adjustment based on creatinine clearance 2
  • Dosing recommendations for adults with renal impairment:
    • Creatinine clearance 50-80 mL/min: 500-1000 mg every 12 hours
    • More severe renal impairment requires further dose reduction

3. Behavioral/Psychiatric Considerations

  • History of psychiatric disorders increases risk of behavioral adverse effects 3
  • Not an absolute contraindication but requires careful monitoring
  • Approximately 6.9% of patients discontinue levetiracetam due to behavioral side effects 3
  • Risk factors for behavioral adverse effects include:
    • History of psychiatric diagnosis
    • Faster titration rates
    • Symptomatic generalized epilepsy

4. Pregnancy and Breastfeeding

  • Not contraindicated but requires risk-benefit assessment
  • Should be used during pregnancy only if potential benefit justifies potential risk to fetus

Important Monitoring Considerations

Behavioral Monitoring

  • Monitor for irritability, agitation, and other behavioral changes, especially in:
    • Patients with intellectual disability
    • Patients with psychiatric history
    • Approximately 12-15% of patients may experience behavioral adverse effects 2

Renal Function

  • Regular monitoring of renal function is recommended
  • Dose adjustments should be made based on creatinine clearance values 4

Seizure Control

  • Levetiracetam has a favorable safety profile with common adverse effects including:
    • Somnolence (10.5-15.2%)
    • Asthenia
    • Dizziness 2
  • About 89% of patients do not report significant adverse effects after loading dose 2

Clinical Pearls

  • Levetiracetam has minimal protein binding and lacks cytochrome P450 isoenzyme-inducing potential, resulting in minimal drug interactions 5
  • Unlike older antiepileptic drugs (AEDs), levetiracetam is considered a non-enzyme-inducing AED (NEIAED) and is preferred over enzyme-inducing AEDs in patients with brain tumors who are receiving chemotherapy 6
  • Slower titration should be considered in patients at higher risk for behavioral side effects 3
  • In overdose cases, levetiracetam can cause sedation and respiratory depression, but recovery is typically rapid with supportive care 7

Levetiracetam is generally well-tolerated with a favorable safety profile compared to older antiepileptic medications, making it a common choice for seizure management in various clinical scenarios when not contraindicated by hypersensitivity.

References

Guideline

Seizure Management in CVA Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

A case of levetiracetam (Keppra) poisoning with clinical and toxicokinetic data.

Journal of toxicology. Clinical toxicology, 2002

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.