Indication
- FELBATOL (felbamate) should not be used as initial therapy in epilepsy (see Warnings in full Prescribing Information).
- FELBATOL is recommended for use only in those patients who do not respond well to other treatments and whose epilepsy is so severe that the potential risk of developing aplastic anemia (a severe blood disorder) or liver failure is outweighed by the potential benefit of felbamate treatment.
- After the patient or their caregiver has discussed the potential risks of Felbatol treatment with their doctor and have provided written consent, FELBATOL treatment can be considered. FELBATOL, by itself or in combination with other drugs is approved for the treatment of partial seizures, with or without generalization, in adults with epilepsy, and as combination therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome in children.
Important Risk Information
- FELBATOL should not be used in patients with a history of any blood or liver problems.
- Routine blood tests should be performed that can help identify potential blood or liver problems.
- FELBATOL should be discontinued if there is evidence that blood or liver problems have occurred.
- Monitor for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
- The most common adverse experiences observed in clinical studies are loss of appetite, vomiting, insomnia, nausea, headache, and sleepiness.
Please see the full Prescribing Information for additional safety information.
WARNING
1. APLASTIC ANEMIA
THE USE OF FELBATOL® (felbamate) IS ASSOCIATED WITH A
MARKED INCREASE IN THE INCIDENCE OF APLASTIC
ANEMIA. ACCORDINGLY, FELBATOL® SHOULD ONLY BE
USED IN PATIENTS WHOSE EPILEPSY IS SO SEVERE THAT
THE RISK OF APLASTIC ANEMIA IS DEEMED ACCEPTABLE IN
LIGHT OF THE BENEFITS CONFERRED BY ITS USE (SEE
INDICATIONS). ORDINARILY, A PATIENT SHOULD NOT BE
PLACED ON AND/OR CONTINUED ON FELBATOL® WITHOUT
CONSIDERATION OF APPROPRIATE EXPERT HEMATOLOGIC
CONSULTATION.
AMONG FELBATOL® TREATED PATIENTS, APLASTIC ANEMIA
(PANCYTOPENIA IN THE PRESENCE OF A BONE MARROW
LARGELY DEPLETED OF HEMATOPOIETIC PRECURSORS)
OCCURS AT AN INCIDENCE THAT MAY BE MORE THAN A 100
FOLD GREATER THAN THAT SEEN IN THE UNTREATED
POPULATION (I.E., 2 TO 5 PER MILLION PERSONS PER
YEAR). THE RISK OF DEATH IN PATIENTS WITH APLASTIC
ANEMIA GENERALLY VARIES AS A FUNCTION OF ITS
SEVERITY AND ETIOLOGY; CURRENT ESTIMATES OF THE
OVERALL CASE FATALITY RATE ARE IN THE RANGE OF 20 TO
30%, BUT RATES AS HIGH AS 70% HAVE BEEN REPORTED IN
THE PAST.
THERE ARE TOO FEW FELBATOL® ASSOCIATED CASES, AND
TOO LITTLE KNOWN ABOUT THEM TO PROVIDE A RELIABLE
ESTIMATE OF THE SYNDROME’S INCIDENCE OR ITS CASE
FATALITY RATE OR TO IDENTIFY THE FACTORS, IF ANY, THAT
MIGHT CONCEIVABLY BE USED TO PREDICT WHO IS AT
GREATER OR LESSER RISK.
IN MANAGING PATIENTS ON FELBATOL®, IT SHOULD BE
BORNE IN MIND THAT THE CLINICAL MANIFESTATION OF
APLASTIC ANEMIA MAY NOT BE SEEN UNTIL AFTER A
PATIENT HAS BEEN ON FELBATOL® FOR SEVERAL MONTHS
(E.G., ONSET OF APLASTIC ANEMIA AMONG FELBATOL®
EXPOSED PATIENTS FOR WHOM DATA ARE AVAILABLE HAS
RANGED FROM 5 TO 30 WEEKS). HOWEVER, THE INJURY TO
BONE MARROW STEM CELLS THAT IS HELD TO BE
ULTIMATELY RESPONSIBLE FOR THE ANEMIA MAY OCCUR
WEEKS TO MONTHS EARLIER. ACCORDINGLY, PATIENTS
WHO ARE DISCONTINUED FROM FELBATOL® REMAIN AT
RISK FOR DEVELOPING ANEMIA FOR A VARIABLE, AND
UNKNOWN, PERIOD AFTERWARDS.
IT IS NOT KNOWN WHETHER OR NOT THE RISK OF
DEVELOPING APLASTIC ANEMIA CHANGES WITH DURATION
OF EXPOSURE. CONSEQUENTLY, IT IS NOT SAFE TO ASSUME
THAT A PATIENT WHO HAS BEEN ON FELBATOL® WITHOUT
SIGNS OF HEMATOLOGIC ABNORMALITY FOR LONG
PERIODS OF TIME IS WITHOUT RISK.
IT IS NOT KNOWN WHETHER OR NOT THE DOSE OF
FELBATOL® AFFECTS THE INCIDENCE OF APLASTIC ANEMIA.
IT IS NOT KNOWN WHETHER OR NOT CONCOMITANT USE OF
ANTIEPILEPTIC DRUGS AND/OR OTHER DRUGS AFFECTS
THE INCIDENCE OF APLASTIC ANEMIA.
APLASTIC ANEMIA TYPICALLY DEVELOPS WITHOUT
PREMONITORY CLINICAL OR LABORATORY SIGNS, THE
FULL BLOWN SYNDROME PRESENTING WITH SIGNS OF
INFECTION, BLEEDING, OR ANEMIA. ACCORDINGLY,
ROUTINE BLOOD TESTING CANNOT BE RELIABLY USED TO
REDUCE THE INCIDENCE OF APLASTIC ANEMIA, BUT, IT
WILL, IN SOME CASES, ALLOW THE DETECTION OF THE
HEMATOLOGIC CHANGES BEFORE THE SYNDROME
DECLARES ITSELF CLINICALLY. FELBATOL® SHOULD BE
DISCONTINUED IF ANY EVIDENCE OF BONE MARROW
DEPRESSION OCCURS.
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2. HEPATIC FAILURE
EVALUATION OF POSTMARKETING EXPERIENCE SUGGESTS
THAT ACUTE LIVER FAILURE IS ASSOCIATED WITH THE USE
OF FELBATOL®. THE REPORTED RATE IN THE U.S. HAS BEEN
ABOUT 6 CASES OF LIVER FAILURE LEADING TO DEATH OR
TRANSPLANT PER 75,000 PATIENT YEARS OF USE. THIS
RATE IS AN UNDERESTIMATE BECAUSE OF UNDER
REPORTING, AND THE TRUE RATE COULD BE
CONSIDERABLY GREATER THAN THIS. FOR EXAMPLE, IF
THE REPORTING RATE IS 10%, THE TRUE RATE WOULD BE
ONE CASE PER 1,250 PATIENT YEARS OF USE.
OF THE CASES REPORTED, ABOUT 67% RESULTED IN
DEATH OR LIVER TRANSPLANTATION, USUALLY WITHIN 5
WEEKS OF THE ONSET OF SIGNS AND SYMPTOMS OF LIVER
FAILURE. THE EARLIEST ONSET OF SEVERE HEPATIC
DYSFUNCTION FOLLOWED SUBSEQUENTLY BY LIVER
FAILURE WAS 3 WEEKS AFTER INITIATION OF FELBATOL®.
ALTHOUGH SOME REPORTS DESCRIBED DARK URINE AND
NONSPECIFIC PRODROMAL SYMPTOMS (E.G., ANOREXIA,
MALAISE, AND GASTROINTESTINAL SYMPTOMS), IN
OTHER REPORTS IT WAS NOT CLEAR IF ANY PRODROMAL
SYMPTOMS PRECEDED THE ONSET OF JAUNDICE.
IT IS NOT KNOWN WHETHER OR NOT THE RISK OF
DEVELOPING HEPATIC FAILURE CHANGES WITH DURATION
OF EXPOSURE.
IT IS NOT KNOWN WHETHER OR NOT THE DOSAGE OF
FELBATOL® AFFECTS THE INCIDENCE OF HEPATIC FAILURE.
IT IS NOT KNOWN WHETHER CONCOMITANT USE OF OTHER
ANTIEPILEPTIC DRUGS AND/OR OTHER DRUGS AFFECT THE
INCIDENCE OF HEPATIC FAILURE.
FELBATOL® SHOULD NOT BE PRESCRIBED FOR ANYONE
WITH A HISTORY OF HEPATIC DYSFUNCTION.
TREATMENT WITH FELBATOL® SHOULD BE INITIATED ONLY
IN INDIVIDUALS WITHOUT ACTIVE LIVER DISEASE AND
WITH NORMAL BASELINE SERUM TRANSAMINASES. IT
HAS NOT BEEN PROVED THAT PERIODIC SERUM
TRANSAMINASE TESTING WILL PREVENT SERIOUS INJURY
BUT IT IS GENERALLY BELIEVED THAT EARLY DETECTION
OF DRUG-INDUCED HEPATIC INJURY ALONG WITH
IMMEDIATE WITHDRAWAL OF THE SUSPECT DRUG
ENHANCES THE LIKELIHOOD FOR RECOVERY. THERE IS NO
INFORMATION AVAILABLE THAT DOCUMENTS HOW
RAPIDLY PATIENTS CAN PROGRESS FROM NORMAL LIVER
FUNCTION TO LIVER FAILURE, BUT OTHER DRUGS KNOWN
TO BE HEPATOTOXINS CAN CAUSE LIVER FAILURE RAPIDLY
(E.G., FROM NORMAL ENZYMES TO LIVER FAILURE IN 2-4
WEEKS). ACCORDINGLY, MONITORING OF SERUM
TRANSAMINASE LEVELS (AST AND ALT) IS RECOMMENDED
AT BASELINE AND PERIODICALLY THEREAFTER. WHILE THE
MORE FREQUENT THE MONITORING THE GREATER THE
CHANCES OF EARLY DETECTION, THE PRECISE SCHEDULE
FOR MONITORING IS A MATTER OF CLINICAL JUDGEMENT.
FELBATOL® SHOULD BE DISCONTINUED IF EITHER SERUM
AST OR SERUM ALT LEVELS BECOME INCREASED = 2
TIMES THE UPPER LIMIT OF NORMAL, OR IF CLINICAL
SIGNS AND SYMPTOMS SUGGEST LIVER FAILURE (SEE
PRECAUTIONS). PATIENTS WHO DEVELOP EVIDENCE OF
HEPATOCELLULAR INJURY WHILE ON FELBATOL® AND ARE
WITHDRAWN FROM THE DRUG FOR ANY REASON SHOULD
BE PRESUMED TO BE AT INCREASED RISK FOR LIVER
INJURY IF FELBATOL® IS REINTRODUCED. ACCORDINGLY,
SUCH PATIENTS SHOULD NOT BE CONSIDERED FOR RETREATMENT.
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