Contraindications for Keppra (Levetiracetam)
The only absolute contraindication to Keppra is a history of hypersensitivity to levetiracetam or any inactive ingredient in the formulation. 1
Absolute Contraindication
- Prior hypersensitivity reaction to levetiracetam or any inactive ingredients in the tablet formulation is the sole FDA-labeled contraindication. 1
Critical Clinical Considerations (Not Absolute Contraindications, But Require Caution)
While not formal contraindications, several clinical scenarios warrant heightened vigilance or consideration of alternative agents:
Psychiatric History
- Patients with pre-existing psychiatric disorders, particularly schizoaffective disorder, bipolar disorder, or history of psychosis, are at significantly increased risk for behavioral adverse effects. 2
- Levetiracetam induces psychiatric side effects in 13.3% of adults, with severe symptoms (depression, agitation, hostility) occurring in 0.7%, and psychosis developing in approximately 1.4% of patients. 2
- Behavioral disturbances including agitation, hostility, paranoia, and psychosis can emerge beyond the initial titration period and represent the most common reason for drug discontinuation. 2
Renal Impairment
- Total body clearance of levetiracetam is decreased in patients with renal impairment, requiring dose modification according to creatinine clearance values. 3
- Since 66% of levetiracetam is eliminated unchanged in urine, renal dysfunction significantly impacts drug clearance. 3
Pregnancy Considerations
- While levetiracetam itself is not contraindicated in pregnancy, valproate (a common alternative antiepileptic) should be avoided in women of childbearing potential due to significantly increased risks of fetal malformations and neurodevelopmental delay. 4
- This makes levetiracetam a preferred option in this population when seizure control is needed. 4
Common Pitfalls to Avoid
- Do not confuse relative caution in psychiatric patients with absolute contraindication—levetiracetam can still be used in these patients with close monitoring, but requires heightened surveillance for behavioral changes. 2
- Do not assume levetiracetam is contraindicated in hepatic impairment—unlike most antiepileptics, levetiracetam undergoes minimal hepatic metabolism via cytochrome P450 and does not require dose adjustment in liver disease. 3
- Do not withhold levetiracetam due to concerns about drug interactions—it has minimal protein binding, lacks cytochrome P450 enzyme-inducing potential, and has no clinically significant pharmacokinetic interactions with other drugs. 5, 3