2005 Safety Alert: Gabitril (tiagabine HCI)

February 14, 2005

Important Drug Warning

Dear Healthcare Provider:

Cephalon, Inc., would like to inform you of important, new safety information for GABITRIL (tiagabine HCI) tablets regarding the risk of new onset seizures and status epilepticus in patients without a history of epilepsy.

From the launch of GABITRIL in 1997 through December 31, 2004 there have been 59 postmarketing reports of seizures in patients without a history of epilepsy.

Clinicians are advised to carefully review the information shown below, which has been added to the GABITRIL prescribing information.

WARNINGS

Seizures in Patients Without Epilepsy: Post-marketing reports have shown that GABITRIL 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, although seizures have been reported in patients taking daily doses of GABITRIL as low as 4 mg/day. In most cases, patients were using concomitant medications (antidepressants, anti psychotics, 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.

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

Safety and effectiveness of GABITRIL have not been established for any indication other than as adjunctive therapy for partial seizures in adults and children 12 years and older.

In nonepileptic patients who develop seizures while on GABITRIL treatment, GABITRIL should be discontinued and patients should be evaluated for an underlying seizure disorder.

Seizures and status epilepticus are known to occur with GABITRIL overdosage (see OVERDOSAGE).

Other changes to the label can be found in the PHARMACOKINETICS, ADVERSE REACTIONS, OVERDOSAGE, and DOSAGE AND ADMINISTRATION sections of the label.

GABITRIL is approved for use only as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures. Because GABITRIL 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. Cephalon does not recommend the use of GABITRIL outside of its approved indication.

Dosing guidelines for GABITRIL have been established only for its use as an adjunctive treatment for partial seizures and not for any other indication. The current dosing guidelines for GABITRIL have been established primarily for patients 12 years and older with partial epilepsy who are taking hepatic enzyme-inducing anticonvulsant drugs. Patients who are not taking enzyme-inducing drugs would have systemic exposure to tiagabine that is higher than expected. Thus, these patients require lower doses of GABITRIL and may require a slower titration rate. Clinicians should exercise caution when prescribing GABITRIL in uninduced patients.

Cephalon is committed to providing you with important information for the safe and effective use of GABITRIL. Cephalon will continue its pharmacovigilance efforts and will work closely with health authorities including the U.S. Food and Drug Administration (FDA) to ensure that appropriate safety information is included in GABITRIL prescribing information.

Enclosed please find the updated prescribing information for GABITRIL.

Should you have any questions regarding this important safety information, please contact Cephalon Professional Services at 1-800-896-5855. As always, we request that serious adverse events be reported to Cephalon at 1-800-896-5855 or to the FDA's MedWatch Adverse Event Reporting. program online at www.fda.gov/MedWatch/report.htm, by phone at 1-800-FDA-1088, or by returning the postage-paid FDA form 3500, which may be downloaded from www.fda.gov/MedWatch/getforms.htm.

Sincerely,

Elizabeth M. Mutisya, MD
Vice President
Medical Affairs

Enclosure:
GABITRIL Tablets Complete Product Information

 

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