Felbamate (Page 3 of 9)

INDICATIONS AND USAGE

Felbamate is not indicated as a first line antiepileptic treatment (see Warnings). Felbamate is recommended for use only in those patients who respond inadequately to alternative treatments and whose epilepsy is so severe that a substantial risk of aplastic anemia and/or liver failure is deemed acceptable in light of the benefits conferred by its use.

If these criteria are met and the patient has been fully advised of the risk, and has provided written acknowledgement, Felbamate can be considered for either monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization, in adults with epilepsy and as adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome in children.

CONTRAINDICATIONS

Felbamate is contraindicated in patients with known hypersensitivity to Felbamate, its ingredients, or known sensitivity to other carbamates. It should not be used in patients with a history of any blood dyscrasia or hepatic dysfunction.

WARNINGS

See Boxed Warning regarding aplastic anemia and hepatic failure.
Antiepileptic drugs should not be suddenly discontinued because of the possibility of increasing seizure frequency.

Suicidal Behavior and Ideation

Antiepileptic drugs (AEDs) including Felbamate, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analyzed.

Table 1 shows absolute and relative risk by indication for all evaluated AEDs.

Table 1 Risk by Indication for Antiepileptic Drugs in the Pooled Analysis

Indication

Placebo Patientswith EventsPer 1000 Patients

Drug Patients withEvents Per1000 Patients

Relative Risk:Incidence ofEvents in DrugPatients/Incidencein Placebo Patients

Risk Difference:Additional DrugPatients withEvents Per 1000Patients

Epilepsy

1.0

3.4

3.5

2.4

Psychiatric

5.7

8.5

1.5

2.9

Other

1.0

1.8

1.9

0.9

Total

2.4

4.3

1.8

1.9

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing Felbamate or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.

PRECAUTIONS

Dosage Adjustment in the Renally Impaired

A study in otherwise healthy individuals with renal dysfunction indicated that prolonged half-life and reduced clearance of felbamate are associated with diminishing renal function. Felbamate should be used with caution in patients with renal dysfunction (see DOSAGE AND ADMINISTRATION).

Information for Patients

Patients should be informed that the use of Felbamate is associated with aplastic anemia and hepatic failure, potentially fatal conditions acutely or over a long term.

The physician should obtain written acknowledgement prior to initiation of Felbamate therapy (see PATIENT/PHYSICIAN ACKNOWLEDGMENT FORM section).

Patients should be instructed to read the Medication Guide supplied as required by law when Felbamate is dispensed. The complete text of the Medication Guide is reprinted at the end of this document.

Aplastic anemia in the general population is relatively rare. The absolute risk for the individual patient is not known with any degree of reliability, but patients on Felbamate may be at more than a 100 fold greater risk for developing the syndrome than the general population.

The long term outlook for patients with aplastic anemia is variable. Although many patients are apparently cured, others require repeated transfusions and other treatments for relapses, and some, although surviving for years, ultimately develop serious complications that sometimes prove fatal (e.g., leukemia).

At present there is no way to predict who is likely to get aplastic anemia, nor is there a documented effective means to monitor the patient so as to avoid and/or reduce the risk. Patients with a history of any blood dyscrasia should not receive Felbamate.

Patients should be advised to be alert for signs of infection, bleeding, easy bruising, or signs of anemia (fatigue, weakness, lassitude, etc.) and should be advised to report to the physician immediately if any such signs or symptoms appear.

Hepatic failure in the general population is relatively rare. The absolute risk for an individual patient is not known with any degree of reliability but patients on Felbamate are at a greater risk for developing hepatic failure than the general population.

At present, there is no way to predict who is likely to develop hepatic failure, however, patients with a history of hepatic dysfunction should not be started on Felbamate.

Patients should be advised to follow their physician’s directives for liver function testing both before starting Felbamate and at frequent intervals while taking Felbamate.

Patients should be advised to be alert for signs of liver dysfunction (jaundice, anorexia, gastrointestinal complaints, malaise, etc.) and to report them to their doctor immediately if they should occur.

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