Kepreptol Drug Interactions

Available data in children did not suggest impact on growth and puberty. However, long term effects on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children remain unknown. In vitro data on metabolic interactions indicate that Levetiracetam is unlikely to produce, or be subject to pharmacokinetic interactions. Levetiracetam and its major metabolite, at concentrations well above Cmax levels achieved within the therapeutic dose range, are neither inhibitors of nor high affinity substrates for human liver cytochrome P450 isoforms, epoxide hydrolase or UDP-glucuronidation enzymes. In addition, levetiracetam does not affect the in vitro glucuronidation of valproic acid. Levetiracetam circulates largely unbound (<10% bound) to plasma proteins; clinically significant interactions with other drugs through competition for protein binding sites are therefore unlikely.
Other Antiepileptic Drugs: Potential drug interactions between Levetiracetam and other AEDs (phenytoin, carbamazepine, valproate, phenobarbital, lamotrigine, gabapentin and primidone) were also assessed by evaluating the serum concentrations of levetiracetam and these AEDs during placebo-controlled clinical studies. These data indicate that levetiracetam does not influence the plasma concentration of other AEDs and that these AEDs do not influence the pharmacokinetics of levetiracetam.
Oral Contraceptives: Levetiracetam (500 mg twice daily) did not influence the pharmacokinetics of an oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, or of the luteinizing hormone and progesterone levels, indicating that impairment of contraceptive efficacy is unlikely. Co-administration of this oral contraceptive did not influence the pharmacokinetics of levetiracetam.
Digoxin: Levetiracetam (1000 mg twice daily) did not influence the pharmacokinetics and pharmacodynamics (ECG) of digoxin given as a 0.25 mg dose every day. Co-administration of digoxin did not influence the pharmacokinetics of levetiracetam.
Warfarin: Levetiracetam (1000 mg twice daily) did not influence the pharmacokinetics of R and S warfarin. Prothrombin time was not affected by levetiracetam. Co-administration of warfarin did not affect the pharmacokinetics of levetiracetam.
Probenecid: Probenecid, a renal tubular secretion blocking agent, administered at a dose of 500 mg four times a day, did not change the pharmacokinetics of levetiracetam 1000 mg twice daily. Cssmax of the metabolite, ucb L057, was approximately doubled in the presence of probenecid while the fraction of drug excreted unchanged in the urine remained the same.
DRURenal clearance of ucb L057 in the presence of probenecid decreased 60%, probably related to competitive inhibition of tubular secretion of ucb L057. The effect of levetiracetam on probenecid was not studied.
Pharmacokinetics of levetiracetam in pediatric patients: As in adults, there is no evidence of clinically significant medicinal product interactions in pediatric patients receiving up to 60 mg/kg/day levetiracetam. A retrospective assessment of pharmacokinetic interactions in children and adolescents with epilepsy (4 to 17 years) confirmed that adjunctive therapy with orally administered levetiracetam did not influence the steady-state serum concentrations of concomitantly administered carbamazepine and valproate. However, data suggested a 22% higher levetiracetam clearance in children taking enzyme-inducing antiepileptic medicinal products. Dose adjustment is not required.
Others: No data on the influence of antacids on the absorption of levetiracetam are available. The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced.