Levetiracetam and Rhabdomyolysis: A Rare but Clinically Significant Adverse Effect

Levetiracetam (Keppra) is an antiepileptic medication known for its relatively safe side effect profile. While rhabdomyolysis represents an uncommon adverse reaction to Keppra, with only limited case reports in the literature, the relationship between levetiracetam dosage and rhabdomyolysis risk remains poorly characterized. This case report describes a patient who developed rhabdomyolysis in apparent correlation with levetiracetam dose. We present a 29-year-old African American male with no significant past medical history who presented to the emergency department following a witnessed seizure. He had experienced two similar episodes several months prior, for which levetiracetam 500 mg twice daily was initiated. The patient reported full adherence to his prescribed medication regimen. Physical examination revealed no significant abnormalities aside from evidence of tongue laceration. Laboratory investigations demonstrated therapeutic levetiracetam levels (26 mcg/mL), creatine phosphokinase (CPK) of 2,835 IU/L, and mildly elevated serum creatinine (1.27 mg/dL). The levetiracetam dosage was subsequently increased to 750 mg twice daily. On day 1 following dose escalation, CPK levels nearly quadrupled to 10,116 IU/L despite aggressive fluid resuscitation, and further rose to 14,400 IU/L on day 2 with concurrent worsening of renal function. Given concern that the increased levetiracetam dose may be contributory, the medication was withheld for one day and then resumed at the original home dose. Despite continued fluid resuscitation, CPK levels continued to rise, reaching a peak of 22,904 IU/L on day 5 before beginning to decline on day 6. By day 7 of hospitalization, CPK levels had decreased substantially. The patient was discharged on day 8 once CPK levels had reached a nadir and was referred to neurology for ongoing management.