NDC 0037-0430 Felbatol

Felbamate

NDC Product Code 0037-0430

NDC CODE: 0037-0430

Proprietary Name: Felbatol What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Felbamate What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • Felbamate is used to treat severe seizures. This medication should be used only when you cannot take other medications or when other medications have not been able to control your seizures. Felbamate is known as an anticonvulsant or anti-epileptic drug.

Product Characteristics

Color(s):
YELLOW (C48330)
Shape: CAPSULE (C48336)
Size(s):
16 MM
Imprint(s):
0430
Score: 2

NDC Code Structure

  • 0037 - Meda Pharmaceuticals

NDC 0037-0430-01

Package Description: 100 TABLET in 1 BOTTLE, PLASTIC

NDC Product Information

Felbatol with NDC 0037-0430 is a a human prescription drug product labeled by Meda Pharmaceuticals. The generic name of Felbatol is felbamate. The product's dosage form is tablet and is administered via oral form.

Labeler Name: Meda Pharmaceuticals

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Felbatol Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • FELBAMATE 400 mg/1

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.
  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Anti-epileptic Agent - [EPC] (Established Pharmacologic Class)
  • Decreased Central Nervous System Disorganized Electrical Activity - [PE] (Physiologic Effect)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Meda Pharmaceuticals
Labeler Code: 0037
FDA Application Number: NDA020189 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 07-29-1993 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

End Marketing Date: 11-30-2022 What is the End Marketing Date?
This is the date the product will no longer be available on the market. If a product is no longer being manufactured, in most cases, the FDA recommends firms use the expiration date of the last lot produced as the EndMarketingDate, to reflect the potential for drug product to remain available after manufacturing has ceased. Products that are the subject of ongoing manufacturing will not ordinarily have any EndMarketingDate. Products with a value in the EndMarketingDate will be removed from the NDC Directory when the EndMarketingDate is reached.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Information for Patients

Felbamate

Felbamate is pronounced as (fel bam' ate)

Why is felbamate medication prescribed?
Felbamate is used to treat certain seizures in adults and children with epilepsy whose seizures have not improved with other treatments. It is used alone or in combinatio...
[Read More]

* Please review the disclaimer below.

Felbatol Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

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.

Description

Felbatol® (felbamate) is an antiepileptic available as
400 mg and 600 mg tablets and as a 600 mg/5 mL suspension for oral
administration. Its chemical name is 2-phenyl-1,3-propanediol
dicarbamate.Felbamate is a white to off-white crystalline powder with a
characteristic odor. It is very slightly soluble in water, slightly
soluble in ethanol, sparingly soluble in methanol, and freely soluble in
dimethyl sulfoxide. The molecular weight is 238.24; felbamate's
molecular formula is C 11 H 14 N 2 O
4 ; its structural formula is:The inactive ingredients for Felbatol® (felbamate)
Tablets 400 mg and 600 mg are starch, microcrystalline cellulose,
croscarmellose sodium, lactose, magnesium stearate, FD&C Yellow
No. 6, D&C Yellow No. 10, and FD&C Red No. 40 (600 mg
tablets only). The inactive ingredients for Felbatol®
(felbamate) Oral Suspension 600 mg/5 mL are sorbitol, glycerin,
microcrystalline cellulose, carboxymethylcellulose sodium, simethicone,
polysorbate 80, methylparaben, saccharin sodium, propylparaben,
FD&C Yellow No. 6, FD&C Red No. 40, flavorings, and
purified water.

Mechanism Of Action:

The mechanism by which felbamate exerts its
anticonvulsant activity is unknown, but in animal test systems
designed to detect anticonvulsant activity, felbamate has
properties in common with other marketed anticonvulsants.
Felbamate is effective in mice and rats in the maximal
electroshock test, the subcutaneous pentylenetetrazol seizure
test, and the subcutaneous picrotoxin seizure test. Felbamate
also exhibits anticonvulsant activity against seizures induced
by intracerebroventricular administration of glutamate in rats
and N-methyl-D,L-aspartic acid in mice. Protection against
maximal electroshock-induced seizures suggests that felbamate
may reduce seizure spread, an effect possibly predictive of
efficacy in generalized tonic-clonic or partial seizures.
Protection against pentylenetetrazol-induced seizures suggests
that felbamate may increase seizure threshold, an effect
considered to be predictive of potential efficacy in absence
seizures.Receptor-binding studies in
vitro indicate that felbamate has weak inhibitory
effects on GABA-receptor binding, benzodiazepine receptor
binding, and is devoid of activity at the MK-801 receptor
binding site of the NMDA receptor-ionophore complex. However,
felbamate does interact as an antagonist at the
strychnine-insensitive glycine recognition site of the NMDA
receptor-ionophore complex. Felbamate is not effective in
protecting chick embryo retina tissue against the neurotoxic
effects of the excitatory amino acid agonists NMDA, kainate, or
quisqualate in vitro. The monocarbamate, p-hydroxy, and 2-hydroxy metabolites
were inactive in the maximal electroshock-induced seizure test
in mice. The monocarbamate and p-hydroxy metabolites had only
weak (0.2 to 0.6) activity compared with felbamate in the
subcutaneous pentylenetetrazol seizure test. These metabolites
did not contribute significantly to the anticonvulsant action of
felbamate.

Pharmacokinetics:

The numbers in the pharmacokinetic section are mean
± standard deviation. Felbamate is well-absorbed after oral administration.
Over 90% of the radioactivity after a dose of 1000 mg
14 C felbamate was found in the urine. Absolute
bioavailability (oral vs. parenteral) has not been measured. The
tablet and suspension were each shown to be bioequivalent to the
capsule used in clinical trials, and pharmacokinetic parameters
of the tablet and suspension are similar. There was no effect of
food on absorption of the tablet; the effect of food on
absorption of the suspension has not been evaluated.Following oral administration, felbamate is the
predominant plasma species (about 90% of plasma
radioactivity). About 40-50% of absorbed dose appears
unchanged in urine, and an additional 40% is present as
unidentified metabolites and conjugates. About 15% is
present as parahydroxyfelbamate, 2-hydroxyfelbamate, and
felbamate monocarbamate, none of which have significant
anticonvulsant activity.Binding of felbamate to human plasma protein was
independent of felbamate concentrations between 10 and 310
micrograms/mL. Binding ranged from 22% to 25%,
mostly to albumin, and was dependent on the albumin
concentration.Felbamate is excreted with a terminal half-life of 20-23
hours, which is unaltered after multiple doses. Clearance after
a single 1200 mg dose is 26±3 mL/hr/kg, and after
multiple daily doses of 3600 mg is 30±8 mL/hr/kg. The
apparent volume of distribution was 756±82 mL/kg after
a 1200 mg dose. Felbamate Cmax and AUC are proportionate to dose
after single and multiple doses over a range of 100-800 mg
single doses and 1200-3600 mg daily doses. Cmin (trough) blood
levels are also dose proportional. Multiple daily doses of 1200,
2400, and 3600 mg gave Cmin values of 30±5,
55±8, and 83±21 micrograms/mL (N=10 patients).
Linear and dose proportional pharmacokinetics were also observed
at doses above 3600 mg/day up to the maximum dose studied of
6000 mg/day. Felbamate gave dose proportional steady-state peak
plasma concentrations in children age 4-12 over a range of 15,
30, and 45 mg/kg/day with peak concentrations of 17, 32, and 49
micrograms/mL.The effects of race and gender on felbamate
pharmacokinetics have not been systematically evaluated, but
plasma concentrations in males (N=5) and females (N=4) given
felbamate have been similar. The effects of felbamate kinetics
on hepatic functional impairment have not been evaluated.Renal Impairment:Felbamate's single dose monotherapy pharmacokinetic parameters
were evaluated in 12 otherwise healthy individuals with renal
impairment. There was a 40-50% reduction in total body
clearance and 9-15 hours prolongation of half-life in renally
impaired subjects compared to that in subjects with normal renal
function. Reduced felbamate clearance and a longer half-life
were associated with diminishing renal function.

Pharmacodynamics:

Typical Physiologic
Responses: 1. Cardiovascular: In adults, there is no effect of
felbamate on blood pressure. Small but statistically significant
mean increases in heart rate were seen during adjunctive therapy
and monotherapy; however, these mean increases of up to 5 bpm
were not clinically significant. In children, no clinically
relevant changes in blood pressure or heart rate were seen
during adjunctive therapy or monotherapy with felbamate.2. Other Physiologic
Effects: The only other change in vital signs was
a mean decrease of approximately 1 respiration per minute in
respiratory rate during adjunctive therapy in children. In
adults, statistically significant mean reductions in body weight
were observed during felbamate monotherapy and adjunctive
therapy. In children, there were mean decreases in body weight
during adjunctive therapy and monotherapy; however, these mean
changes were not statistically significant. These mean
reductions in adults and children were approximately 5% of the
mean weights at baseline.

Clinical Studies

The results of controlled clinical trials established the
efficacy of Felbatol® (felbamate) as monotherapy and adjunctive
therapy in adults with partial-onset seizures with or without secondary
generalization and in partial and generalized seizures associated with
Lennox-Gastaut syndrome in children.

Felbatol® Monotherapy Trials In Adults

Felbatol® (3600 mg/day given QID) and low-dose
valproate (15 mg/kg/day) were compared as monotherapy during a
112-day treatment period in a multicenter and a single-center
double-blind efficacy trial. Both trials were conducted
according to an identical study design. During a 56-day baseline
period, all patients had at least four partial-onset seizures
per 28 days and were receiving one antiepileptic drug at a
therapeutic level, the most common being carbamazepine. In the
multicenter trial, baseline seizure frequencies were 12.4 per 28
days in the Felbatol® group and 21.3 per 28 days in the
low-dose valproate group. In the single-center trial, baseline
seizure frequencies were 18.1 per 28 days in the
Felbatol® group and 15.9 per 28 days in the low-dose
valproate group. Patients were converted to monotherapy with
Felbatol® or low-dose valproic acid during the first 28
days of the 112-day treatment period. Study endpoints were
completion of 112 study days or fulfilling an escape criterion.
Criteria for escape relative to baseline were: (1) twofold
increase in monthly seizure frequency, (2) twofold increase in
highest 2-day seizure frequency, (3) single generalized
tonic-clonic seizure (GTC) if none occurred during baseline, or
(4) significant prolongation of GTCs. The primary efficacy
variable was the number of patients in each treatment group who
met escape criteria.In the multicenter trial, the percentage of patients who
met escape criteria was 40% (18/45) in the
Felbatol® group and 78% (39/50) in the low-dose
valproate group. In the single-center trial, the percentage of
patients who met escape criteria was 14% (3/21) in the
Felbatol® group and 90% (19/21) in the low-dose
valproate group. In both trials, the difference in the
percentage of patients meeting escape criteria was statistically
significant (P<.001) in favor of Felbatol®.
These two studies by design were intended to demonstrate the
effectiveness of Felbatol® monotherapy. The studies
were not designed or intended to demonstrate comparative
efficacy of the two drugs. For example, valproate was not used
at the maximally effective dose.

Felbatol® Adjunctive Therapy Trials In Adults

A double-blind, placebo-controlled crossover trial
consisted of two 10-week outpatient treatment periods. Patients
with refractory partial-onset seizures who were receiving
phenytoin and carbamazepine at therapeutic levels were
administered Felbatol® (felbamate) as add-on therapy at
a starting dosage of 1400 mg/day in three divided doses, which
was increased to 2600 mg/day in three divided doses. Among the
56 patients who completed the study, the baseline seizure
frequency was 20 per month. Patients treated with
Felbatol® had fewer seizures than patients treated with
placebo for each treatment sequence. There was a 23%
(P=.018) difference in percentage seizure frequency reduction in
favor of Felbatol®.Felbatol® 3600 mg/day given QID and placebo were
compared in a 28-day double-blind add-on trial in patients who
had their standard antiepileptic drugs reduced while undergoing
evaluations for surgery of intractable epilepsy. All patients
had confirmed partial-onset seizures with or without
generalization, seizure frequency during surgical evaluation not
exceeding an average of four partial seizures per day or more
than one generalized seizure per day, and a minimum average of
one partial or generalized tonic-clonic seizure per day for the
last 3 days of the surgical evaluation. The primary efficacy
variable was time to fourth seizure after randomization to
treatment with Felbatol® or placebo. Thirteen
(46%) of 28 patients in the Felbatol® group
versus 29 (88%) of 33 patients in the placebo group
experienced a fourth seizure. The median times to fourth seizure
were greater than 28 days in the Felbatol® group and 5
days in the placebo group. The difference between
Felbatol® and placebo in time to fourth seizure was
statistically significant (P=.002) in favor of
Felbatol®.

Felbatol® Adjunctive Therapy Trial In Children With Lennox-Gastaut Syndrome

In a 70-day double-blind, placebo-controlled add-on trial
in the Lennox-Gastaut syndrome, Felbatol® 45 mg/kg/day
given QID was superior to placebo in controlling the multiple
seizure types associated with this condition. Patients had at
least 90 atonic and/or atypical absence seizures per month while
receiving therapeutic dosages of one or two other antiepileptic
drugs. Patients had a past history of using an average of eight
antiepileptic drugs. The most commonly used antiepileptic drug
during the baseline period was valproic acid. The frequency of
all types of seizures during the baseline period was 1617 per
month in the Felbatol® group and 716 per month in the
placebo group. Statistically significant differences in the
effect on seizure frequency favored Felbatol® over
placebo for total seizures (26% reduction vs. 5%
increase, P<.001), atonic seizures (44% reduction
vs. 7% reduction, P=.002), and generalized tonic-clonic
seizures (40% reduction vs. 12% increase,
P=.017). Parent/guardian global evaluations based on impressions
of quality of life with respect to alertness, verbal
responsiveness, general well-being, and seizure control
significantly (P<.001) favored Felbatol® over
placebo.When efficacy was analyzed by gender in four
well-controlled trials of felbamate as adjunctive and
monotherapy for partial-onset seizures and Lennox-Gastaut
syndrome, a similar response was seen in 122 males and 142
females.

Indications And Usage

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 acknowledgement,
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.

Contraindications

Felbatol® is contraindicated in patients with known
hypersensitivity to Felbatol®, 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 Felbatol
®, 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 AnalysisIndicationPlacebo Patientswith EventsPer 1000
PatientsDrug Patients withEvents Per1000
PatientsRelative Risk:Incidence ofEvents in
DrugPatients/Incidencein Placebo PatientsRisk Difference:Additional
DrugPatients withEvents Per 1000PatientsEpilepsy1.03.43.52.4Psychiatric5.78.51.52.9Other1.01.81.90.9Total2.44.31.81.9The 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 Felbatol 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.

Other

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).

Suicidal Thinking and
Behavior: Patients, their caregivers, and families
should be counseled that AEDs, including Felbatol®, may
increase the risk of suicidal thoughts and behavior and should
be advised of the need to be alert for the emergence or
worsening of 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.

Pregnancy: Patients
should be encouraged to enroll in the North American
Antiepileptic Drug (NAAED) Pregnancy Registry if they become
pregnant. This registry is collecting information about the
safety of antiepileptic drugs during pregnancy. To enroll,
patients can call the toll free number 1-888-233-2334 (see
Pregnancy section).

Information For Patients

Information for
Patients: Patients should be informed that the use of
Felbatol® 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 Felbatol® therapy (see PATIENT/PHYSICIAN ACKNOWLEDGMENT FORM section).Patients should be instructed to read the Medication Guide supplied as required by law when
Felbatol® 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 Felbatol® 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 Felbatol®.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 Felbatol® 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 Felbatol®.Patients should be advised to follow their physician's
directives for liver function testing both before starting
Felbatol® (felbamate) and at frequent intervals while
taking Felbatol®.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.

Laboratory Tests

Laboratory Tests:
Full hematologic
evaluations should be performed before
Felbatol® therapy, frequently during therapy, and for a
significant period of time after discontinuation of
Felbatol® therapy. While it might appear prudent to
perform frequent CBCs in patients continuing on
Felbatol®, there is no evidence that such monitoring
will allow early detection of marrow suppression before aplastic
anemia occurs. (See Boxed Warnings). Complete pretreatment blood counts, including
platelets and reticulocytes should be obtained as a baseline. If
any hematologic abnormalities are detected during the course of
treatment, immediate consultation with a hematologist is
advised. Felbatol® should be discontinued if any
evidence of bone marrow depression occurs.See Box
Warnings for recommended monitoring of serum
transaminases. If significant, confirmed liver abnormalities are
detected during the course of Felbatol® treatment,
Felbatol® should be discontinued immediately with
continued liver function monitoring until values return to
normal. (see PATIENT/PHYSICIAN ACKNOWLEDGMENT FORM).

Drug Interactions

Drug Interactions:The drug interaction data described in this section were
obtained from controlled clinical trials and studies involving
otherwise healthy adults with epilepsy.Use in Conjunction with Other
Antiepileptic Drugs (see DOSAGE
AND ADMINISTRATION): The addition of
Felbatol® to antiepileptic drugs (AEDs) affects the
steady-state plasma concentrations of AEDs. The
net effect of these interactions is summarized in Table 2:Table 2 Steady-State Plasma Concentrations of Felbatol
When Coadministered With Other AEDs*Not administered but an
active metabolite of carbamazepine.**No significant
effect.AEDCoadministeredAEDConcentrationFelbatol®ConcentrationPhenytoin↑↓Valproate↑↔**Carbamazepine (CBZ)*CBZ epoxide↓↑↓Phenobarbital↑↓Specific Effects of
Felbatol® on Other Antiepileptic Drugs:Phenytoin:
Felbatol® causes an increase in steady-state phenytoin
plasma concentrations. In 10 otherwise healthy subjects with
epilepsy ingesting phenytoin, the steady-state trough (Cmin)
phenytoin plasma concentration was 17±5 micrograms/mL.
The steady-state Cmin increased to 21±5 micrograms/mL
when 1200 mg/day of felbamate was coadministered. Increasing the
felbamate dose to 1800 mg/day in six of these subjects increased
the steady-state phenytoin Cmin to 25±7 micrograms/mL.
In order to maintain phenytoin levels, limit adverse
experiences, and achieve the felbamate dose of 3600 mg/day, a
phenytoin dose reduction of approximately 40% was
necessary for eight of these 10 subjects.In a controlled clinical trial, a 20% reduction
of the phenytoin dose at the initiation of Felbatol®
therapy resulted in phenytoin levels comparable to those prior
to Felbatol® administration.Carbamazepine: Felbatol® causes a decrease
in the steady-state carbamazepine plasma concentrations and an
increase in the steady-state carbamazepine epoxide plasma
concentration. In nine otherwise healthy subjects with epilepsy
ingesting carbamazepine, the steady-state trough (Cmin)
carbamazepine concentration was 8±2 micrograms/mL. The
carbamazepine steady-state Cmin decreased 31% to
5±1 micrograms/mL when felbamate (3000 mg/day, divided
into three doses) was coadministered. Carbamazepine epoxide
steady-state Cmin concentrations increased 57% from
1.0±0.3 to 1.6±0.4 micrograms/mL with the
addition of felbamate.In clinical trials, similar changes in carbamazepine and
carbamazepine epoxide were seen.Valproate:
Felbatol® causes an increase in steady-state valproate
concentrations. In four subjects with epilepsy ingesting
valproate, the steady-state trough (Cmin) valproate plasma
concentration was 63±16 micrograms/mL. The steady-state
Cmin increased to 78±14 micrograms/mL when 1200 mg/day
of felbamate was coadministered. Increasing the felbamate dose
to 2400 mg/day increased the steady-state valproate Cmin to
96±25 micrograms/mL. Corresponding values for free
valproate Cmin concentrations were 7±3, 9±4,
and 11±6 micrograms/mL for 0, 1200, and 2400 mg/day
Felbatol®, respectively. The ratios of the AUCs of
unbound valproate to the AUCs of the total valproate were
11.1%, 13.0%, and 11.5%, with
coadministration of 0, 1200, and 2400 mg/day of
Felbatol®, respectively. This indicates that the
protein binding of valproate did not change appreciably with
increasing doses of Felbatol®. Phenobarbital: Coadministration of felbamate with
phenobarbital causes an increase in phenobarbital plasma
concentrations. In 12 otherwise healthy male volunteers
ingesting phenobarbital, the steady-state trough (Cmin)
phenobarbital concentration was 14.2 micrograms/mL. The
steady-state Cmin concentration increased to 17.8 micrograms/mL
when 2400 mg/day of felbamate was coadministered for one week.Effects of Other
Antiepileptic Drugs on Felbatol®:Phenytoin:
Phenytoin causes an approximate doubling of the clearance of
Felbatol® (felbamate) at steady-state and, therefore,
the addition of phenytoin causes an approximate 45%
decrease in the steady-state trough concentrations of
Felbatol® as compared to the same dose of
Felbatol® given as monotherapy.Carbamazepine: Carbamazepine causes an approximate
50% increase in the clearance of Felbatol® at
steady-state and, therefore, the addition of carbamazepine
results in an approximate 40% decrease in the
steady-state trough concentrations of Felbatol® as
compared to the same dose of Felbatol® given as
monotherapy. Valproate:
Available data suggest that there is no significant effect of
valproate on the clearance of Felbatol® at
steady-state. Therefore, the addition of valproate is not
expected to cause a clinically important effect on
Felbatol® (felbamate) plasma concentrations.Phenobarbital: It appears that phenobarbital may
reduce plasma felbamate concentrations. Steady-state plasma
felbamate concentrations were found to be 29% lower than
the mean concentrations of a group of newly diagnosed subjects
with epilepsy also receiving 2400 mg of felbamate a day.Effects of Antacids on
Felbatol®: The rate and extent of
absorption of a 2400 mg dose of Felbatol® as
monotherapy given as tablets was not affected when
coadministered with antacids.Effects of Erythromycin on
Felbatol®: The coadministration of
erythromycin (1000 mg/day) for 10 days did not alter the
pharmacokinetic parameters of Cmax, Cmin, AUC, Cl/kg or tmax at
felbamate daily doses of 3000 or 3600 mg/day in 10 otherwise
healthy subjects with epilepsy.Effects of Felbatol®
on Low-Dose Combination Oral Contraceptives: A group of 24 nonsmoking, healthy white female volunteers
established on an oral contraceptive regimen containing 30
µg ethinyl estradiol and 75 µg gestodene for
at least 3 months received 2400 mg/day of felbamate from
midcycle (day 15) to midcycle (day 14) of two consecutive oral
contraceptive cycles. Felbamate treatment resulted in a
42% decrease in the gestodene AUC 0-24, but no
clinically relevant effect was observed on the pharmacokinetic
parameters of ethinyl estradiol. No volunteer showed hormonal
evidence of ovulation, but one volunteer reported intermenstrual
bleeding during felbamate treatment.

Drug & Or Laboratory Test Interactions

Drug/Laboratory Test
Interactions: There are no known interactions of
Felbatol® with commonly used laboratory
tests.

Carcinogenesis & Mutagenesis & Impairment Of Fertility

Carcinogenesis, Mutagenesis,
Impairment of Fertility: Carcinogenicity studies
were conducted in mice and rats. Mice received felbamate as a
feed admixture for 92 weeks at doses of 300, 600, and 1200 mg/kg
and rats were also dosed by feed admixture for 104 weeks at
doses of 30, 100, and 300 (males) or 10, 30, and 100 (females)
mg/kg. The maximum doses in these studies produced steady-state
plasma concentrations that were equal to or less than the
steady-state plasma concentrations in epileptic patients
receiving 3600 mg/day. There was a statistically significant
increase in hepatic cell adenomas in high-dose male and female
mice and in high-dose female rats. Hepatic hypertrophy was
significantly increased in a dose-related manner in mice,
primarily males, but also in females. Hepatic hypertrophy was
not found in female rats. The relationship between the
occurrence of benign hepatocellular adenomas and the finding of
liver hypertrophy resulting from liver enzyme induction has not
been examined. There was a statistically significant increase in
benign interstitial cell tumors of the testes in high-dose male
rats receiving felbamate. The relevance of these findings to
humans is unknown.As a result of the synthesis process, felbamate could
contain small amounts of two known animal carcinogens, the
genotoxic compound ethyl carbamate (urethane) and the
nongenotoxic compound methyl carbamate. It is theoretically
possible that a 50 kg patient receiving 3600 mg of felbamate
could be exposed to up to 0.72 micrograms of urethane and 1800
micrograms of methyl carbamate. These daily doses are
approximately 1/35,000 (urethane) and 1/5,500 (methyl carbamate)
on a mg/kg basis, and 1/10,000 (urethane) and 1/1,600 (methyl
carbamate) on a mg/m2 basis, of the dose levels shown
to be carcinogenic in rodents. Any presence of these two
compounds in felbamate used in the lifetime carcinogenicity
studies was inadequate to cause tumors. Microbial and mammalian cell assays revealed no evidence
of mutagenesis in the Ames Salmonella /microsome plate test, CHO/HGPRT
mammalian cell forward gene mutation assay, sister chromatid
exchange assay in CHO cells, and bone marrow cytogenetics assay. Reproduction and fertility studies in rats showed no
effects on male or female fertility at oral doses of up to 13.9
times the human total daily dose of 3600 mg on a mg/kg basis, or
up to 3 times the human total daily dose on a mg/m2
basis.

Pregnancy

Pregnancy: Pregnancy Category
C. The incidence of malformations was not
increased compared to control in offspring of rats or rabbits
given doses up to 13.9 times (rat) and 4.2 times (rabbit) the
human daily dose on a mg/kg basis, or 3 times (rat) and less
than 2 times (rabbit) the human daily dose on a mg/m
2 basis. However, in rats, there was a decrease in
pup weight and an increase in pup deaths during lactation. The
cause for these deaths is not known. The no effect dose for rat
pup mortality was 6.9 times the human dose on a mg/kg basis or
1.5 times the human dose on a mg/m 2 basis.Placental transfer of felbamate occurs in rat pups. There
are, however, no studies in pregnant women. Because animal
reproduction studies are not always predictive of human
response, this drug should be used during pregnancy only if
clearly needed.To provide information regarding the effects of in utero
exposure to Felbatol®, physicians are advised to
recommend that pregnant patients taking Felbatol enroll in the
NAAED Pregnancy Registry. This can be done by calling the toll
free number 1-888-233-2334, and must be done by patients
themselves. Information on the registry can also be found at the
website http://www.aedpregnancyregistry.org/.

Labor & Delivery

Labor and Delivery:
The effect of felbamate on labor and delivery in humans is
unknown.

Nursing Mothers

Nursing Mothers:
Felbamate has been detected in human milk. The effect on the
nursing infant is unknown (see Pregnancy section).

Pediatric Use

Pediatric Use: The
safety and effectiveness of Felbatol® in children other
than those with Lennox-Gastaut syndrome has not been
established.

Geriatric Use

Geriatric Use: No
systematic studies in geriatric patients have been conducted.
Clinical studies of Felbatol® did not include
sufficient numbers of patients aged 65 and over to determine
whether they respond differently from younger patients. Other
reported clinical experience has not identified differences in
responses between the elderly and younger patients. In general,
dosage selection for an elderly patient should be cautious,
usually starting at the low end of the dosing range, reflecting
the greater frequency of decreased hepatic, renal, or cardiac
function, and of concomitant disease or other drug
therapy.

Adverse Reactions

To report SUSPECTED ADVERSE REACTIONS, contact
Meda Pharmaceuticals Inc. at 1-800-526-3840 or FDA at 1-800-FDA-1088
or www.fda.gov/medwatch .The most common adverse reactions seen in association with
Felbatol® (felbamate) in adults during monotherapy are
anorexia, vomiting, insomnia, nausea, and headache. The most common
adverse reactions seen in association with Felbatol® in adults
during adjunctive therapy are anorexia, vomiting, insomnia, nausea,
dizziness, somnolence, and headache.The most common adverse reactions seen in association with
Felbatol® in children during adjunctive therapy are anorexia,
vomiting, insomnia, headache, and somnolence.The dropout rate because of adverse experiences or intercurrent
illnesses among adult felbamate patients was 12 percent (120/977). The
dropout rate because of adverse experiences or intercurrent illnesses
among pediatric felbamate patients was six percent (22/357). In adults,
the body systems associated with causing these withdrawals in order of
frequency were: digestive (4.3%), psychological (2.2%),
whole body (1.7%), neurological (1.5%), and
dermatological (1.5%). In children, the body systems associated
with causing these withdrawals in order of frequency were: digestive
(1.7%), neurological (1.4%), dermatological
(1.4%), psychological (1.1%), and whole body
(1.0%). In adults, specific events with an incidence of
1% or greater associated with causing these withdrawals, in
order of frequency were: anorexia (1.6%), nausea (1.4%),
rash (1.2%), and weight decrease (1.1%). In children,
specific events with an incidence of 1% or greater associated
with causing these withdrawals, in order of frequency was rash
(1.1%).Incidence in Clinical
Trials: The prescriber should be aware that the figures
cited in the following table cannot be used to predict the incidence of
side effects in the course of usual medical practice where patient
characteristics and other factors differ from those which prevailed in
the clinical trials. Similarly, the cited frequencies cannot be compared
with figures obtained from other clinical investigations involving
different investigators, treatments, and uses including the use of
Felbatol® (felbamate) as adjunctive therapy where the incidence
of adverse events may be higher due to drug interactions. The cited
figures, however, do provide the prescribing physician with some basis
for estimating the relative contribution of drug and nondrug factors to
the side effect incidence rate in the population studied.AdultsIncidence in Controlled Clinical
Trials--Monotherapy Studies in Adults: The table
that follows enumerates adverse events that occurred at an incidence of
2% or more among 58 adult patients who received
Felbatol® monotherapy at dosages of 3600 mg/day in double-blind
controlled trials. Table 3 presents reported adverse events that were
classified using standard WHO-based dictionary terminology.Table 3 Adults Treatment-Emergent Adverse Event Incidence in
Controlled Monotherapy Trials*3600 mg/day;** 15 mg/kg/day Felbatol®* (N=58)Low Dose Valproate** (N=50)Body System Event%%Body as a
Whole  Fatigue  Weight
Decrease  Face Edema 6.93.43.4 4.000Central Nervous
System  Insomnia  Headache  Anxiety 8.66.95.2 4.018.02.0Dermatological  Acne  Rash 3.43.4 00Digestive  Dyspepsia  Vomiting  Constipation  Diarrhea  SGPT
Increased 8.68.66.95.25.2 2.02.02.002.0Metabolic/Nutritional  Hypophosphatemia 3.4 0Respiratory  Upper Respiratory Tract
Infection  Rhinitis 8.66.9 4.00Special
Senses  Diplopia  Otitis
Media 3.43.4 4.00Urogenital  Intramenstrual
Bleeding  Urinary Tract Infection 3.43.4 02.0Incidence in Controlled Add-On Clinical
Studies in Adults: Table 4 enumerates adverse events that occurred at an incidence of
2% or more among 114 adult patients who received
Felbatol® adjunctive therapy in add-on controlled trials at
dosages up to 3600 mg/day. Reported adverse events were classified using
standard WHO-based dictionary terminology.Many adverse experiences that occurred during adjunctive therapy
may be a result of drug interactions. Adverse experiences during
adjunctive therapy typically resolved with conversion to monotherapy, or
with adjustment of the dosage of other antiepileptic drugs.Table 4 Adults Treatment-Emergent Adverse Event Incidence in
Controlled Add-On Trials Felbatol®Placebo(N=114)(N=43)Body System/Event%%Body as a
Whole  Fatigue  Fever  Chest
Pain 16.82.62.6 7.04.70Central Nervous
System  Headache  Somnolence  Dizziness  Insomnia  Nervousness  Tremor  Anxiety  Gait
Abnormal  Depression  Paraesthesia  Ataxia  Mouth
Dry  Stupor 36.819.318.417.57.06.15.35.35.33.53.52.62.6 9.37.014.07.02.32.34.7002.3000Dermatological  Rash 3.5 4.7Digestive  Nausea  Anorexia  Vomiting  Dyspepsia  Constipation  Diarrhea  Abdominal
Pain  SGPT Increased 34.219.316.712.311.45.35.33.5 2.32.34.77.02.32.300Musculoskeletal  Myalgia 2.6 0Respiratory  Upper Respiratory Tract
Infection  Sinusitis  Pharyngitis 5.33.52.6 7.000Special
Senses  Diplopia  Taste
Perversion  Vision Abnormal 6.16.15.3 002.3ChildrenIncidence in a Controlled Add-On Trial in
Children with Lennox-Gastaut Syndrome: Table 5
enumerates adverse events that occurred more than once among 31
pediatric patients who received Felbatol® up to 45 mg/kg/day or
a maximum of 3600 mg/day. Reported adverse events were classified using
standard WHO-based dictionary terminology.Table 5 Children Treatment-Emergent Adverse Event Incidence in
Controlled Add-On Lennox-Gastaut Trials Felbatol®Placebo(N=31)(N=27)Body System/Event %%Body as a
Whole  Fever  Fatigue  Weight
Decrease  Pain  22.69.76.56.5  11.13.700 Central Nervous
System  Somnolence  Insomnia  Nervousness  Gait
Abnormal  Headache  Thinking
Abnormal  Ataxia  Urinary
Incontinence  Emotional
Lability  Miosis  48.416.116.19.76.56.56.56.56.56.5  11.114.818.5018.53.73.77.400
Dermatological  Rash  9.7 7.4Digestive  Anorexia  Vomiting  Constipation  Hiccup  Nausea  Dyspepsia  54.838.712.99.76.56.5  14.814.803.703.7
Hematologic  Purpura  Leukopenia  12.96.5  7.40 Respiratory  Upper Respiratory Tract
Infection  Pharyngitis  Coughing  45.29.76.5  25.93.70 Special Senses  Otitis Media  9.7  0Other Events Observed in Association
with the Administration of Felbatol®
(felbamate): In the paragraphs that follow, the adverse
clinical events, other than those in the preceding tables, that occurred
in a total of 977 adults and 357 children exposed to Felbatol®
(felbamate) and that are reasonably associated with its use are
presented. They are listed in order of decreasing frequency. Because the
reports cite events observed in open-label and uncontrolled studies, the
role of Felbatol® in their causation cannot be reliably
determined.Events are classified within body system categories and
enumerated in order of decreasing frequency using the following
definitions: frequent adverse events are defined as those occurring on
one or more occasions in at least 1/100 patients; infrequent adverse
events are those occurring in 1/100-1/1000 patients; and rare events are
those occurring in fewer than 1/1000 patients.Event frequencies are calculated as the number of patients
reporting an event divided by the total number of patients (N=1334)
exposed to Felbatol®.Body as a Whole:Frequent: Weight increase,
asthenia, malaise, influenza-like symptoms; Rare: anaphylactoid reaction, chest pain substernal. Cardiovascular:Frequent: Palpitation,
tachycardia; Rare:
supraventricular tachycardia. Central Nervous System:Frequent: Agitation,
psychological disturbance, aggressive reaction: Infrequent: hallucination, euphoria,
suicide attempt, migraine. Digestive:Frequent: SGOT increased;
Infrequent: esophagitis,
appetite increased; Rare: GGT
elevated. Hematologic:Infrequent: Lymphadenopathy,
leukopenia, leukocytosis, thrombocytopenia, granulocytopenia; Rare: antinuclear factor test
positive, qualitative platelet disorder, agranulocytosis. Metabolic/Nutritional:Infrequent: Hypokalemia,
hyponatremia, LDH increased, alkaline phosphatase increased,
hypophosphatemia; Rare:
creatinine phosphokinase increased.Musculoskeletal:Infrequent: Dystonia. Dermatological:Frequent: Pruritus; Infrequent: urticaria, bullous
eruption; Rare: buccal mucous
membrane swelling, Stevens-Johnson Syndrome. Special Senses:Rare: Photosensitivity allergic
reaction. Postmarketing Adverse Event
Reports: Voluntary reports of adverse events in patients
taking Felbatol® (usually in conjunction with other drugs) have
been received since market introduction and may have no causal
relationship with the drug(s). These include the following by body
system: Body as a Whole: neoplasm,
sepsis, L.E. syndrome, SIDS, sudden death, edema, hypothermia, rigors,
hyperpyrexia. Cardiovascular: atrial
fibrillation, atrial arrhythmia, cardiac arrest, torsade de pointes,
cardiac failure, hypotension, hypertension, flushing, thrombophlebitis,
ischemic necrosis, gangrene, peripheral ischemia, bradycardia,
Henoch-Schönlein purpura (vasculitis). Central & Peripheral Nervous
System: delusion, paralysis, mononeuritis, cerebrovascular
disorder, cerebral edema, coma, manic reaction, encephalopathy, paranoid
reaction, nystagmus, choreoathetosis, extrapyramidal disorder,
confusion, psychosis, status epilepticus, dyskinesia, dysarthria,
respiratory depression, apathy, concentration impaired.Dermatological: abnormal
body odor, sweating, lichen planus, livedo reticularis, alopecia, toxic
epidermal necrolysis. Digestive: (Refer to
WARNINGS ) hepatitis, hepatic failure, G.I. hemorrhage,
hyperammonemia, pancreatitis, hematemesis, gastritis, rectal hemorrhage,
flatulence, gingival bleeding, acquired megacolon, ileus, intestinal
obstruction, enteritis, ulcerative stomatitis, glossitis, dysphagia,
jaundice, gastric ulcer, gastric dilatation, gastroesophageal reflux.Fetal Disorders: fetal
death, microcephaly, genital malformation, anencephaly, encephalocele. Hematologic: (Refer to
WARNINGS ) increased and decreased prothrombin time, anemia,
hypochromic anemia, aplastic anemia, pancytopenia, hemolytic uremic
syndrome, increased mean corpuscular volume (mcv) with and without
anemia, coagulation disorder, embolism-limb, disseminated intravascular
coagulation, eosinophilia, hemolytic anemia, leukemia, including
myelogenous leukemia, and lymphoma, including T-cell and B-cell
lymphoproliferative disorders.Metabolic/Nutritional:
hypernatremia, hypoglycemia, SIADH, hypomagnesemia, dehydration,
hyperglycemia, hypocalcemia. Musculoskeletal:
arthralgia, muscle weakness, involuntary muscle contraction,
rhabdomyolysis. Respiratory: dyspnea,
pneumonia, pneumonitis, hypoxia, epistaxis, pleural effusion,
respiratory insufficiency, pulmonary hemorrhage, asthma.Special Senses:
hemianopsia, decreased hearing, conjunctivitis. Urogenital: menstrual
disorder, acute renal failure, hepatorenal syndrome, hematuria, urinary
retention, nephrosis, vaginal hemorrhage, abnormal renal function,
dysuria, placental disorder.

Abuse

Abuse: Abuse
potential was not evaluated in human studies.

Dependence

Dependence: Rats
administered felbamate orally at doses 8.3 times the recommended
human dose 6 days each week for 5 consecutive weeks demonstrated
no signs of physical dependence as measured by weight loss
following drug withdrawal on day 7 of each week.

Overdosage

Four subjects inadvertently received Felbatol®
(felbamate) as adjunctive therapy in dosages ranging from 5400 to 7200
mg/day for durations between 6 and 51 days. One subject who received
5400 mg/day as monotherapy for 1 week reported no adverse experiences.
Another subject attempted suicide by ingesting 12,000 mg of
Felbatol® in a 12-hour period. The only adverse experiences
reported were mild gastric distress and a resting heart rate of 100 bpm.
No serious adverse reactions have been reported. General supportive
measures should be employed if overdosage occurs. It is not known if
felbamate is dialyzable.

Dosage And Administration

Felbatol® (felbamate) has been studied as monotherapy
and adjunctive therapy in adults and as adjunctive therapy in children
with seizures associated with Lennox-Gastaut syndrome. As
Felbatol® is added to or substituted for existing AEDs, it is
strongly recommended to reduce the dosage of those AEDs in the range of
20-33% to minimize side effects (see Drug
Interactions subsection).Dosage Adjustment in the Renally
Impaired: Felbamate should be used with caution in
patients with renal dysfunction. In the renally impaired, starting and
maintenance doses should be reduced by one-half (see CLINICAL
PHARMACOLOGY / Pharmacokinetics and PRECAUTIONS ). Adjunctive therapy with medications which affect felbamate
plasma concentrations, especially AEDs, may warrant further reductions
in felbamate daily doses in patients with renal dysfunction.Adults (14 years of age and
over) The majority of patients received 3600 mg/day
in clinical trials evaluating its use as both monotherapy and adjunctive
therapy.Monotherapy: (Initial
therapy) Felbatol® (felbamate) has not been systematically
evaluated as initial monotherapy. Initiate Felbatol® at 1200
mg/day in divided doses three or four times daily. The prescriber is
advised to titrate previously untreated patients under close clinical
supervision, increasing the dosage in 600-mg increments every 2 weeks to
2400 mg/day based on clinical response and thereafter to 3600 mg/day if
clinically indicated.Conversion to Monotherapy:
Initiate Felbatol® at 1200 mg/day in divided doses three or
four times daily. Reduce the dosage of concomitant AEDs by one-third at
initiation of Felbatol® therapy. At week 2, increase the
Felbatol® dosage to 2400 mg/day while reducing the dosage of
other AEDs up to an additional one-third of their original dosage. At
week 3, increase the Felbatol® dosage up to 3600 mg/day and
continue to reduce the dosage of other AEDs as clinically indicated.Adjunctive Therapy:
Felbatol® should be added at 1200 mg/day in divided doses three
or four times daily while reducing present AEDs by 20% in order
to control plasma concentrations of concurrent phenytoin, valproic acid,
phenobarbital, and carbamazepine and its metabolites. Further reductions
of the concomitant AEDs dosage may be necessary to minimize side effects
due to drug interactions. Increase the dosage of Felbatol® by
1200 mg/day increments at weekly intervals to 3600 mg/day. Most side
effects seen during Felbatol® adjunctive therapy resolve as the
dosage of concomitant AEDs is decreased.Table 6 Dosage Table (adults)*See Adjunctive and Conversion to Monotherapy sections.Dosage reduction of concomitant AEDsWEEK
1REDUCE original dose by20–33%*WEEK
2REDUCE original dose byup to an
additional 1/3*WEEK
3REDUCE asclinicallyindicatedFelbatol®Dosage1200 mg/day Initial dose2400 mg/dayTherapeutic dosage range3600 mg/dayTherapeutic dosage rangeWhile the above Felbatol® conversion guidelines may
result in a Felbatol® 3600 mg/day dose within 3 weeks, in some
patients titration to a 3600 mg/day Felbatol® dose has been
achieved in as little as 3 days with appropriate adjustment of other
AEDs.Children with Lennox-Gastaut
Syndrome (Ages 2-14 years)Adjunctive Therapy:
Felbatol® should be added at 15 mg/kg/day in divided doses
three or four times daily while reducing present AEDs by 20% in
order to control plasma levels of concurrent phenytoin, valproic acid,
phenobarbital, and carbamazepine and its metabolites. Further reductions
of the concomitant AEDs dosage may be necessary to minimize side effects
due to drug interactions. Increase the dosage of Felbatol® by
15 mg/kg/day increments at weekly intervals to 45 mg/kg/day. Most side
effects seen during Felbatol® adjunctive therapy resolve as the
dosage of concomitant AEDs is decreased.

How Supplied

Felbatol® (felbamate) Tablets, 400 mg, are yellow,
scored, capsule-shaped tablets, debossed 0430 on one side and FELBATOL
400 on the other; available in bottles of 100 (NDC 0037-0430-01).
Felbatol® (felbamate) Tablets, 600 mg, are peach-colored,
scored, capsule-shaped tablets, debossed 0431 on one side and FELBATOL
600 on the other; available in bottles of 100 (NDC 0037-0431-01).
Felbatol® (felbamate) Oral Suspension, 600 mg/5 mL, is
peach-colored; available in 8 oz bottles (NDC 0037-0442-67) and 32 oz
bottles (NDC 0037-0442-17).Shake suspension well before using. Store at controlled room
temperature 20°-25°C (68°-77°F).
Dispense in tight container.To report SUSPECTED ADVERSE REACTIONS, contact
Meda Pharmaceuticals Inc. at 1-800-526-3840 or FDA at 1-800-FDA-1088
or www.fda.gov/medwatch.MEDA Pharmaceuticals® MEDA Pharmaceuticals Inc.
Somerset, NJ 08873
IN-00431-18     Rev.
7/11

Patient/Physician Acknowledgment Form

FELBATOL® (felbamate) SHOULD NOT BE USED BY PATIENTS UNTIL THERE HAS BEEN A COMPLETE DISCUSSION OF THE RISKS.
All patients treated with Felbatol should acknowledge that they understand the risks and other information about Felbatol discussed below, and physicians should acknowledge this discussion.
IMPORTANT INFORMATION AND WARNING:
Felbatol®, taken by itself or with other prescription and/or non-prescription drugs, can result in a severe, potentially fatal blood abnormality ("aplastic anemia") and/or severe, potentially fatal liver damage.
PATIENT ACKNOWLEDGMENT: Do not sign this form if there is anything you do not understand about the information you have received. Ask your doctor about anything you do not understand before you initial any of the items below or sign this form. My [My son, daughter, ward                                                    's] treatment with Felbatol® has been personally explained to me by Dr.                                                   . The following points of information, among others, have been specifically discussed and made clear and I have had the opportunity to ask any questions concerning this information: 1. I,                                                    (Patient's Name), understand that Felbatol® is used to treat certain types of seizures and my physician has told me that I have this type(s) of seizures;INITIALS:                                                   2. I understand that Felbatol® is being used because my seizures have not been satisfactorily treated with other antiepileptic drugs;INITIALS:                                                   3. I understand that there is a serious risk that I could develop aplastic anemia and/or liver failure, both of which are potentially fatal, by using Felbatol®;INITIALS:                                                   4. I understand that there are no laboratory tests which will predict if I am at an increased risk for one of the potentially fatal conditions;INITIALS:                                                   5. I understand that I should have the recommended blood work before my treatment with Felbatol® is begun (baseline) and periodically thereafter as clinical judgement warrants. I understand that although this blood work may help detect if I develop one of these conditions, it may do so only after significant, irreversible and potentially fatal damage has already occurred;INITIALS:                                                   6. If I am currently taking other antiepileptic drugs, I understand that the manufacturer of Felbatol® recommends that the dosage of these other drugs be decreased by a certain amount when Felbatol® is started; if my physician determines that this should not be done in my case, he/she has explained the reason(s) for this decision;INITIALS:                                                   7. I understand that I must immediately report any unusual symptoms to Dr.                                                    and be especially aware of any rashes, easy bruising, bleeding, sore throats, fever, and/or dark urine; INITIALS:                                                   8. I understand that antiepileptic drugs such as Felbatol® may increase the risk of suicidal thoughts and behavior. I understand that I must immediately report any unusual changes in mood or behavior, symptoms of depression or thoughts about self-harm to Dr.                                                   .INITIALS:                                                                                                     Patient, Parent, or Guardian                                                  Address                                                  TelephonePHYSICIAN STATEMENT: I have fully explained to the patient,                                                   , the nature and purpose of the treatment with Felbatol® (felbamate) and the potential risks associated with that treatment. I have asked the patient if he/she has any questions regarding this treatment or the risks and have answered those questions to the best of my ability. I also acknowledge that I have read and understand the prescribing information.
                                                                                                     Physician                                                   DateRevised: 7/11 NOTE TO PHYSICIAN: It is strongly recommended that you retain a signed copy of the Patient/Physician Acknowledgment Form with the patient's medical records. SUPPLY OF PATIENT/PHYSICIAN ACKNOWLEDGMENT FORMS: A supply of "Patient/Physician Acknowledgement " Forms as printed above is available, free of charge, from your local MEDA Pharmaceuticals representative, or may be obtained by calling 1-800-526-3840. Permission to use the above Patient/Physician Acknowledgment Form by photocopy reproduction is also hereby granted by MEDA Pharmaceuticals Inc. MEDA Pharmaceuticals® MEDA Pharmaceuticals Inc.Somerset, New Jersey 08873-4120

Medication Guide

  • FELBATOL (Fel-ba-taal)(felbamate)Tablets and Oral SuspensionIS-00431-01                                      Rev. 7/11Read this Medication Guide before you start taking FELBATOL and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.What is the most important information I should know about FELBATOL?Do not stop taking FELBATOL without first talking to your healthcare provider. Stopping FELBATOL suddenly can cause serious problems.FELBATOL can cause serious side effects, including:1. FELBATOL may cause serious blood problems that may be life-threatening.Call your healthcare provider right away if you have any of the following symptoms:Fever, sore throat or other infections that come and go or do not go awayFrequent infections or an infection that does not go awayEasy bruisingRed or purple spots on your bodyBleeding gums or nose bleedsSevere fatigue or weakness2. Liver problems that may be life-threatening. Call your healthcare provider right away if you have any of these symptoms:yellowing of your skin or the whites of your eyes (jaundice)dark urinenausea or vomitingloss of appetitepain on the right side of your stomach (abdomen)3. Like other antiepileptic drugs, FELBATOL may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.     Call your healthcare provider right away if you have any of these symptoms,      especially if they are new, worse, or worry you:thoughts about suicide or dyingattempts to commit suicidenew or worse depressionnew or worse anxietyfeeling agitated or restlesspanic attackstrouble sleeping (insomnia)new or worse irritabilityacting aggressive, being angry, or violentacting on dangerous impulsesan extreme increase in activity and talking (mania)other unusual changes in behavior or moodHow can I watch for early symptoms of suicidal thoughts and actions?Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.Keep all follow-up visits with your healthcare provider as scheduled.Call your healthcare provider between visits as needed, especially if you are worried about symptoms.Do not stop FELBATOL without first talking to a healthcare provider.Stopping FELBATOL suddenly can cause serious problems. You should talk to your health care provider before stopping. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures.Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.What is FELBATOL?FELBATOL is a prescription medicine used when other treatments have failed in:adults alone or with other medicines to treat:
  • Partial seizures with and without generalizationchildren with other medicines to treat:
  • Seizures associated with Lennox-Gastaut syndromeWho should not take FELBATOL?Do not take FELBATOL if you:are allergic to felbamate, carbamates or any of the ingredients in FELBATOL. See the end of this Medication Guide for a complete list of ingredients in FELBATOL.have or have had blood problemshave or have had liver problemsWhat should I tell my healthcare provider before taking FELBATOL?Before you take FELBATOL, tell your healthcare provider if you:have kidney problemshave or have had depression, mood problems, or suicidal thoughts or behaviorhave any other medical conditionsare pregnant or plan to become pregnant. It is not known if FELBATOL can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking FELBATOL. You and your healthcare provider will decide if you should take FELBATOL while you are pregnant.
  • If you become pregnant while taking FELBATOL, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic medicine during pregnancy. You can enroll in this registry by calling 1-888-233-2334.are breastfeeding or plan to breastfeed. FELBATOL may pass into your breast milk. You and your healthcare provider should decide if you should take FELBATOL while you breastfeed.Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.Taking FELBATOL with certain other medicines can cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider.Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.How should I take FELBATOL?Take FELBATOL exactly as your healthcare provider tells you. Your healthcare provider will tell you how much FELBATOL to take and when to take it.Your healthcare provider may change your dose of FELBATOL. Do not change your dose of FELBATOL without talking to your healthcare provider.Because of the risk of serious blood and liver problems, your healthcare provider may do blood tests before you start and while you take FELBATOL.If you take too much FELBATOL, call your healthcare provider or local Poison Control Center right away.Do not stop FELBATOL without first talking to your healthcare provider.What should I avoid while taking FELBATOL?FELBATOL can cause drowsiness and dizziness. Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking FELBATOL, until you talk with your doctor. Taking FELBATOL with alcohol or drugs that cause sleepiness or dizziness may make your sleepiness or dizziness worse.What are the possible side effects of FELBATOL?See “What is the most important information I should know about FELBATOL?”FELBATOL may cause serious side effects including:The most common side effects of FELBATOL include:weight lossvomitingtrouble sleepingnauseadizzinesssleepinessheadachedouble-visionchanges in the way that food tastesThese are not all the possible side effects of FELBATOL. For more information, ask your healthcare provider or pharmacist.Tell your healthcare provider if you have any side effect that bothers you or that does not go away.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should I store FELBATOL?Store FELBATOL at room temperature between 68°F to 77°F (20°C to 25°C).Keep FELBATOL and all medicines out of the reach of children.General information about FELBATOL.Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use FELBATOL for a condition for which it was not prescribed. Do not give FELBATOL to other people, even if they have the same symptoms that you have. It may harm them.This Medication Guide summarizes the most important information about FELBATOL. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about FELBATOL that is written for health professionals.What are the ingredients in FELBATOL?Active Ingredient: felbamateTablet Inactive Ingredients: starch, microcrystalline cellulose, croscarmellose sodium, lactose, magnesium stearate, FD&C yellow No. 6, D&C Yellow No. 10, and FD&C Red No. 40 (600 mg tablets only).Suspension Inactive Ingredients: sorbitol, glycerin, microcrystalline cellulose, carboxymethylcellulose sodium, simethicone, polysorbate 80, methylparaben, saccharain sodium, propylparaben, FD&C Yellow No. 6, FD&C Red No. 40, flavorings, and purified water.For more information, go to www. FELBATOL.com or call 1-800-526-3840.This Medication Guide has been approved by the U.S. Food and Drug Administration.MEDA Pharmaceuticals®                                              Issued 7/11MEDA Pharmaceuticals Inc., Somerset, NJ 08873-4120FELBATOL is a registered trademark of Meda Pharmaceuticals Inc.IS-00431-01                          Rx Only                          Rev. 7/11

* Please review the disclaimer below.