Topiramate + Phenobarbital or Primidone - Drug Interactions

Topiramate appears not to alter pharmacokinetics of phenobarbital or primidone

Clinical evidence,mechanism, importance and management

A review of data from double blind, placebo-controlled studies found that over periods of 8 to 12 weeks plasma levels of phenobarbital or primidone in patients (number not stated) with partial seizures remained unchanged when they were also given topiramate (See reference number 1).

A population pharmacokinetic study reported that patients taking phenobarbital had 31 % lower morning topiramate levels than patients not taking enzyme-inducing antiepileptics (See reference number 2). Another study that grouped carbamazepine,phenobarbital and phenytoin reported that patients taking one or more of these drugs had 1.5-fold greater topiramate clearance than patients taking lamotrigine or valproate (See reference number 3). Phenobarbital probably induces metabolism of topiramate thereby reducing its levels.

When topiramate is added to existing treatment with phenytoin or phenobarbital its dose should be titrated to effect. If phenobarbital or primidone are withdrawn or added, be aware that dose of topiramate may need adjustment.

Doose DR,Walker SA, Pledger G, Lim P, Reife RA. Evaluation of phenobarbital and primidone/phenobarbital (primidone’s active metabolite) plasma concentrations during administration of add-on topiramate therapy in five multicenter, double-blind, placebo-controlled trials inoutpatients with partial seizures. Epilepsia (1995) 36 (Suppl 3), S158.

May TW,Jürges U. Serum concentrations of topiramate in epileptic patients: the influence ofdose and comedication. Epilepsia (1999) 40 (Suppl 2), 249.

Contin M,Riva R, Albani F, Avoni P, Baruzzi A. Topiramate therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit (2002) 24, 332–7.