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Felbatol (Felbamate) - Summary

 
 



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.

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 RE-TREATMENT.

 

FELBATOL SUMMARY

Felbatol® (felbamate) is an antiepileptic available as 400 mg and 600 mg tablets and as a 600 mg/5 mL suspension for oral administration.

Felbatol® is not indicated as a first line antiepileptic treatment (see Warnings). Felbatol® 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, informed consent, Felbatol® 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.


See all Felbatol indications & dosage >>

NEWS HIGHLIGHTS

Media Articles Related to Felbatol (Felbamate)

Low-Dose Fish Oil Shows Reduced Seizures in Epilepsy
Source: Medscape NeurologyHeadlines [2014.09.09]
After several negative trials, the possibility of treating epilepsy with fish oil has seen a glimmer of hope with a new study suggesting a significant benefit with a lower dose than previously tested.
Medscape Medical News

Omega-3 fish oil 'could reduce seizure frequency for epilepsy patients'
Source: Cardiovascular / Cardiology News From Medical News Today [2014.09.09]
A new study by researchers from UCLA School of Medicine suggests consuming low doses of omega-3 fish oil each day could reduce the occurrence of seizures in patients with epilepsy.

Small Study Hints Fish Oil Might Ease Tough-to-Treat Epilepsy
Source: MedicineNet Seizure Specialty [2014.09.09]
Title: Small Study Hints Fish Oil Might Ease Tough-to-Treat Epilepsy
Category: Health News
Created: 9/8/2014 7:36:00 PM
Last Editorial Review: 9/9/2014 12:00:00 AM

New understanding of common cause of sudden death in epilepsy
Source: Cardiovascular / Cardiology News From Medical News Today [2014.09.05]
A gene crucial for brain and heart development may also be associated with sudden unexplained death in epilepsy (SUDEP), the most common cause of early mortality in epilepsy patients.

New mouse line offers new insights for treatments of epilepsy, Alzheimer's
Source: Epilepsy News From Medical News Today [2014.08.25]
University of Utah scientists have developed a genetically engineered line of mice that is expected to open the door to new research on epilepsy, Alzheimer's and other diseases.

more news >>

Published Studies Related to Felbatol (Felbamate)

Felbamate as an add-on therapy for refractory epilepsy. [2011.01.19]
CONCLUSIONS: In view of the methodological deficiencies, limited number of individual studies and differences in outcome measure, we have found no reliable evidence to support the use of felbamate as an add-on therapy in patients with refractory partial-onset epilepsy. A large scale, randomized controlled trial conducted over a greater period of time is required to inform clinical practice.

Felbamate as an add-on therapy for refractory epilepsy. [2011]
CONCLUSIONS: In view of the methodological deficiencies, limited number

Low dose of bupropion significantly enhances the anticonvulsant activity of felbamate, lamotrigine and topiramate in mice. [2011.01.15]
Experimental evidence indicates that bupropion hydrochloride, an antidepressant and a first-line smoking cessation aid, exerts dose-dependently anticonvulsant and convulsant effects.A pharmacokinetic interaction is responsible for the effect of bupropion co-administered with lamotrigine.

[Felbamate crystalluria]. [2010.09]
This report describes the case of an 11-year-old child, who presents crystalluria occurring after several years of treatment with antiepileptic felbamate (Taloxa(R)). The crystalline morphologies observed were very heterogeneous, long and thin needle shapped-crystals or even hairy crystals or large needle asymmetric crystals...

Efficacy of felbamate in the treatment of intractable pediatric epilepsy. [2010.06]
The antiepileptic drug felbamate has demonstrated efficacy against a variety of seizure types in the pediatric population, particularly seizures associated with Lennox-Gastaut syndrome. Postmarketing experience, however, revealed serious idiosyncratic adverse effects not observed during clinical trials, including aplastic anemia and liver failure...

more studies >>

Reports of Suspected Felbatol (Felbamate) Side Effects

Grand MAL Convulsion (7)Decreased Appetite (6)Convulsion (6)Weight Decreased (5)Gastrooesophageal Reflux Disease (5)Condition Aggravated (4)Product Substitution Issue (3)Pyrexia (3)Constipation (3)Treatment Noncompliance (3)more >>


Page last updated: 2014-09-09

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