Topiramate

Additional information

Topiramate is used in focal epilepsy with or without generalization, in primary generalized tonic-clonic seizures, and as a migraine prophylactic.

Pharmacokinetics and dosing

More than 80% of topiramate is eliminated renally. No sex difference in half-life has been observed (11 men/boys, 15 women/girls) [1]. However, in women/girls, the volume of distribution of topiramate is about 50% less than in men/boys, this is attributed to the higher percentage of body fat in women/girls. This difference is not considered to be clinically relevant [1, 2]. The clearance of topiramate in adults is not influenced by patient’s sex or race [3]. No sex differentiation in dosing has been recommended [4]. Topiramate metabolism may increase during pregnancy, see below.

Effects

Studies conducted by the pharmaceutical company have shown no impact of patient’s sex on effectiveness and safety of topiramate, regardless of indication [3]. Five randomized, double-blind, placebo-controlled trials of topiramate as add-on therapy in patients with medically intractable partial-onset seizures showed no difference in efficacy by patient’s sex. However, women represented only 20% of the 534 patients studied [5]. An observational study in pediatric patients (43 boys, 70 girls) with migraine treated for at least three months with topiramate found no association between effect and patient’s sex [6].

Adverse events

Treatment with topiramate may cause weight loss. Some studies suggest that there are no sex differences in weight loss in adults (13 men, 36 women) [7], while other studies indicate that women were more likely to lose weight than men after treatment during 12 months [8, 9].

Paresthesia is a common adverse event of topiramate treatment. A study based on survey data and register data (12 men and 148 women with migraine, 96 men and 64 women with epilepsy) shows that women were twice as likely as men in reporting paresthesia (odds ratio 2.1). Patients with migraine reported more paresthesia than patients with epilepsy (odds ratio 3.5), which may be due to faster titration protocol in migraine than in epileptic patients [8].

Reproductive health issues

Topiramate may reduce the plasma concentration of estrogens and progestins. Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).

Physiologic changes during pregnancy can alter antiepileptic pharmacokinetics and total antiepileptic concentration. Pharmacokinetics of some antiepileptic drugs are more pronounced, probably due to pregnancy-related differential effects on cytochrome P450 enzymes and pregnancy-related changes in the volume of distribution [9]. Topiramate serum concentrations have been reported to decline by up to 30-40% during the third trimester of pregnancy, but with a considerable interindividual variation [10]. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).