levetiracetam and Liver-Cirrhosis--Alcoholic

Levetiracetam is an antiepileptic drug approved for use as adjunctive therapy in adults with partial-onset seizures. We sought to investigate possible changes in the pharmacokinetics of levetiracetam and its metabolite ucb L057 in patients with liver cirrhosis, who may require dose adjustments.. A single dose of levetiracetam was administered to 5 healthy subjects and to patients with Child-Pugh class A (n = 5), B (n = 6), or C (n = 5) alcohol-induced cirrhosis. The pharmacokinetics of levetiracetam and ucb L057 was measured and correlated with biochemical liver function parameters, with creatinine clearance, and with kinetics of caffeine, lidocaine, and d -sorbitol as probes for specific liver functions.. Dynamic liver function tests revealed a deterioration of liver function. The pharmacokinetics of levetiracetam and its metabolite did not differ between healthy subjects and those with class A or B cirrhosis. However, in patients with class C cirrhosis, levetiracetam total clearance was reduced by 57% (90% confidence interval [CI], 43%-67%; P < .001). The geometric mean ratio of the area under the plasma concentration-time curve for levetiracetam, Child-Pugh class C versus control, was 2.41 (90% CI, 1.80-3.23), and the geometric mean of the half-life ratio was 2.27 (90% CI, 1.74-2.97). This was explained by the deterioration of renal function in patients with severe hepatic disease.. In pharmacokinetic studies of hepatic impairment, including all classes of cirrhosis may be more revealing than including only selected classes of liver failure. No dose adjustment of levetiracetam is necessary in patients with mild to moderate liver impairment; however, patients with severe cirrhosis should initially receive only half of the commonly recommended dose.

Topics: Adult; Anticonvulsants; Caffeine; Humans; Kidney Function Tests; Levetiracetam; Lidocaine; Liver Cirrhosis, Alcoholic; Liver Function Tests; Male; Middle Aged; Piracetam; Sorbitol

Selecting an appropriate anticonvulsant for treatment of recipients of orthostatic liver transplants who have new-onset epileptic seizures can be challenging because first-line agents may contribute to worsening encephalopathy, alter the plasma concentration of immunosuppressive agents, and result in hepatotoxicity. We describe the case of a 55-year-old man who underwent orthotopic liver transplantation because of end-stage liver disease due to alcoholic cirrhosis and hepatitis C. He required two repeat transplantation procedures. After the last procedure, epileptic seizures developed, which were initially managed with phenytoin. However, the patient remained stuporous and mental status fluctuated. Breakthrough seizures later developed in the setting of rejection. Levetiracetam (500 mg orally, twice a day) was chosen for its favorable pharmacokinetic properties as an alternative to phenytoin. By the third day of levetiracetam therapy, the patient became more responsive. At most recent follow-up, 3 months after the start of levetiracetam therapy, the patient was still treated with levetiracetam monotherapy, and seizure control was judged to be excellent.

Topics: Anticonvulsants; Hepatitis C; Humans; Levetiracetam; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Middle Aged; Piracetam; Postoperative Complications; Treatment Outcome