Julitam/Julitam I.V. Drug Interactions

Julitam: Tablet: Evidence of significant interactions between Levetiracetam and other epileptics is mostly lacking. However, for the effects of Levetiracetam on carbamazepine, there are symptoms of carbamazepine toxicity due to a pharmacodynamic mechanism as blood levels of carbamazepine and its epoxide metabolite were not affected.
Oral solution: Antiepileptic medicinal products: Pre-marketing data from clinical studies conducted in adults indicate that Levetiracetam Oral Solution did not influence the serum concentrations of existing antiepileptic medicinal products (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these antiepileptic medicinal products did not influence the pharmacokinetics of Levetiracetam Oral Solution.
As in adults, there is no evidence of clinically significant medicinal product interactions in paediatric 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 20% higher levetiracetam clearance in children taking enzyme-inducing antiepileptic medicinal products. Dose adjustment is not required.
Probenecid: Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to inhibit the renal clearance of the primary metabolite, but not of levetiracetam. Nevertheless, the concentration of this metabolite remains low. It is expected that other medicinal products excreted by active tubular secretion could also reduce the renal clearance of the metabolite. The effect of levetiracetam on probenecid was not studied and the effect of levetiracetam on other actively secreted medicinal products, e.g. NSAIDs, sulfonamides and methotrexate, is unknown.
Antacids: No data on the influence of antacids on the absorption of levetiracetam are available.
Food and alcohol: The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was slightly reduced. No data on the interaction of levetiracetam with alcohol are available.
Julitam I.V.: Antiepileptic medicinal products: Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam did not influence the serum concentrations of existing antiepileptic medicinal products (phenytoin, carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these medicinal products did not influence the pharmacokinetics of levetiracetam.
As in adults, there is no clinically significant evidence of drug interaction in pediatric patients treated with doses up to 60 mg/kg/day.
In a retrospective evaluation of pharmacokinetic interaction in children and adolescents (4 to 17 years) with epilepsy, it was confirmed that oral levetiracetam in additional treatment did not affect the steady-state concentration of carbamazepine and valproate. However, data suggest that 20% higher levetiracetam clearance is seen in children receiving enzyme-inducing antiepileptic drugs. No dose adjustment is required.
Probenecid: Probenecid (500 mg 4 times a day), a drug that blocks tubular secretion from the kidney, has been shown to inhibit renal clearance of the primary metabolite but not levetiracetam. However, the concentration of this metabolite remains low.
Methotrexate: It has been reported that co-administration of levetiracetam and methotrexate reduces methotrexate clearance, thereby increasing/prolonging the concentration of methotrexate in the blood to potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in patients taking these two drugs together.
Oral contraceptives and other pharmacokinetic interactions: Levetiracetam 1,000 mg daily did not influence the pharmacokinetics of oral contraceptives (ethinylestradiol and levonorgestrel); endocrine parameters (luteinizing hormone and progesterone) were not modified. Levetiracetam 2,000 mg daily did not influence the pharmacokinetics of digoxin and warfarin; prothrombin times were not modified.
Coadministration with digoxin, oral contraceptives and warfarin did not influence the pharmacokinetics of levetiracetam.
Alcohol: No data on the interaction of levetiracetam with alcohol are available.