Topiramate (Epitomax) was discovered in 1979 by Bruce E. Marianow and Joseph F. Gardocki during their research work at McNeil Pharmaceuticals. Commercial use of Topiramate began in 1996. Mylan Pharmaceuticals received final FDA approval to sell generic topiramate in the United States, and a generic version was released in September 2006.
The indications for use are
- Partial or generalized tonic-clonic seizures in adults and children over 2 years of age, including patients with newly diagnosed epilepsy (as monotherapy or in combination with other anticonvulsants);
- seizures associated with Lennox-Gastaud syndrome in adults and children over 2 years of age (as part of complex therapy);
- Prevention of migraine attacks in adults.
The drug is approved for use in children over 2 years of age. Influence on driving and operating machinery The drug should be administered with caution in patients engaged in potentially hazardous activities that require increased attention and rapid psychomotor reactions, because the drug may cause drowsiness and dizziness.
Adequate and strictly controlled clinical safety studies of Epitomax in pregnancy have not been conducted. Nevertheless, the use of the drug in pregnancy is possible only when the expected benefits to the mother exceed the potential risk to the fetus.
Excretion of Epitomax with the breast milk has not been studied in controlled studies. The limited number of observations suggests that Epitomax is excreted with breast milk. If use of Epitomax during lactation is necessary, discontinuation of breastfeeding should be considered.
- Children under 2 years of age;
- Childhood under 6 years of age for monotherapy, under 3 years for combined therapy of epilepsy;
- Children under 18 years of age when used for migraine prophylaxis;
- prophylaxis of migraine in pregnant women or women of childbearing age who do not use effective contraception;
- Hypersensitivity to the drug components.
Caution: renal failure, hepatic failure, hypercalciuria, nephrourolithiasis (including anamnesis or family history).
After oral administration, Epitomax is rapidly and effectively absorbed from the gastrointestinal tract. The bioavailability calculated based on the radioactive label yield after administration of 100 mg of 14C-Epitomax was 81%. Food intake has no clinically significant effect on the bioavailability of the drug.
Distribution of the drug
Binding to plasma proteins is 13-17%. After a single oral dose up to 1200 mg, mean Vd is 0.55-0.8 l/kg. The Vd value depends on gender. In women, the values are about 50% of those observed in men, which is associated with a higher content of adipose tissue in women. After a single oral administration, Epitomax pharmacokinetics is linear, plasma clearance remains constant at 20-30 ml/min, and AUC in dose range from 100 mg to 400 mg increases in proportion to the dose. In patients with normal renal function, it may take 4 to 8 days to reach equilibrium.
Metabolism of the drug. About 20% of Epitomax is biotransformed to form 6 metabolites, 2 of which mostly retain the structure of Epitomax and either have no or minimal anticonvulsant activity.
Excretion of the drug. Epitomax and its metabolites are excreted primarily with the urine. After multiple doses of 50 and 100 mg twice daily, the average T1/2 was 21 hours.