United States of America - The manufacturer of tiagabine hydrochlorine (Gabitril®) has informed prescribers of important new safety information regarding the risk of new onset seizures and status epilepticus in patients without a history of epilepsy. Since the launch of tiagabine in 1997 through 2004, there have been 59 postmarketing reports of such seizures. Clinicians are advised to carefully review the newly added information. Safety and effectiveness of tiagabine have not been established for any indication other than as adjunctive therapy for partial seizures in adults and children 12 years and older.

Seizures in patients without epilepsy

Post-marketing reports have shown that tiagabine use has been associated with new onset seizures and status epilepticus in patients without epilepsy. Dose may be an important predisposing factor in the development of seizures which have been reported in patients taking daily doses as low as 4 mg/day. In most cases, patients were using concomitant medications (antidepressants, antipsychotics, stimulants, narcotics) that are thought to lower the seizure threshold. Some seizures occurred near the time of a dose increase, even after periods of prior stable dosing.

Dosing recommendations in current labelling for treatment of epilepsy are based on use in patients with partial seizures 12 years of age and older, most of whom were taking enzyme-inducing antiepileptic drugs (AEDs; e.g., carbamazepine, phenytoin, primidone and phenobarbital) which lower plasma levels of tiagabine by inducing its metabolism. Use of tiagabine without enzyme-inducing antiepileptic drugs results in blood levels about twice those attained in the studies on which current dosing recommendations are based.

In nonepileptic patients who develop seizures, tiagabine should be discontinued and patients should be evaluated for an underlying seizure disorder. Seizures and status epilepticus are known to occur with tiagabine overdosage.

Tiagabine is approved for use only as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Because tiagabine has not been systematically evaluated in adequate and well-controlled clinical trials for any other indication, its safety and effectiveness have not been established for any other use. The manufacturer does not recommend the use of tiagabine outside of its approved indication.

Reference: Communication from Cephalon, Inc., 14 February 2005 available on http://www.fda.gov/MedWatch/getforms.htm.