Topiramate

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Topamax (Janssen-Cilag)
25 mg, 50 mg, 100 mg and 200 mg tablets

Indication: epilepsy

Although therapy with a single drug is preferred for patients with epilepsy, this may not be enough to control their seizures. Topiramate adds to the choice of drugs which may be used as adjunctive treatment. It is specifically approved for adults with partial onset epileptic seizures with or without secondary generalised seizures.

Topiramate is based on a monosaccharide molecule. It is thought to act by increasing the activity of gamma-aminobutyric acid (GABA), blocking sodium channels to reduce the frequency of action potentials, and inhibiting a subtype of glutamate receptors.

The efficacy of topiramate is based on 5 randomised placebo-controlled, double-blind parallel group studies. In one of the larger studies, 181 patients were randomised to receive either placebo or topiramate (200 mg, 400 mg or600 mg daily) as adjunctive therapy. Once stabilised, the dose was continued for 12 weeks. The rate of seizures per month declined significantly, compared with placebo, in patients taking 400 mg (48% decline) or 600 mg (45% decline).Between 40% and 50% of the patients on these doses had their seizure rate at least halved.1

Therapy begins with a dose of 50 mg at night. This is then increased weekly by 50-100 mg depending on the clinical response. Twice a day dosing is recommended.

The tablets are well absorbed. There is some metabolism, but most of the drug is excreted unchanged in the urine. The elimination half-life is 21 hours. Clearance is decreased in patients with renal disease and, although less than 20% of the drug is metabolised, liver disease. Currently, the need for plasma level monitoring is uncertain. Adding topiramate usually has no effect on the steady state concentrations of carbamazepine, phenobarbitone, phenytoin, primidone or sodium valproate. Occasionally, some patients with a particular enzyme will develop increased phenytoin concentrations. Both phenytoin and carbamazepine reduce the plasma concentration of topiramate. Other drugs with the potential for interaction include digoxin and low-dose oral contraceptives.

The most common adverse effects include ataxia, confusion, dizziness, fatigue, paraesthesia, impaired concentration and abnormal thinking. Patients should be cautioned about driving or operating machines. They should also be advised that there is a risk of forming renal stones. Although regular laboratory tests are not required, topiramate can cause changes in the white cell count.

There are no data on the efficacy or safety of topiramate in combination with gabapentin, lamotrigine or vigabatrin. It is also unclear which is the most effective adjunctive drug.

References

  1. Faught E, Wilder BJ, Ramsay RE, Reife RA, Kramer LD, Pledger GW, et al. Topiramate placebo-controlled dose-ranging trial in refractory partial epilepsy using 200, 400, and 600 mg daily dosages. Neurology1996;46:1684-90.