Felbatol

This medication should not be prescribed for other uses; ask your doctor or pharmacist for more information.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

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.

Felbatol is part of the drug class:

• Other antiepileptics

Tell your healthcare provider if you are 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.

• Risk of aplastic anemia; importance of notifying clinicians if signs of infection, bleeding, easy bruising, or signs of anemia (e.g., fatigue, weakness, lassitude) occur.27

• Risk of hepatic failure; importance of immediately notifying clinicians if signs of liver dysfunction (e.g., jaundice, anorexia, GI complaints, malaise) occur38 and of adhering to prescribed schedule of liver function tests.27

• Risk of suicidality (anticonvulsants, including felbamate, may increase risk of suicidal thoughts or actions in about 1 in 500 people).35 39 40 Importance of patients, family, and caregivers being alert to day-to-day changes in mood, behavior, and actions and immediately informing clinician of any new or worrisome behaviors (e.g., talking or thinking about wanting to hurt oneself or end one’s life, withdrawing from friends and family, becoming depressed or experiencing worsening of existing depression, becoming preoccupied with death and dying, giving away prized possessions).35 40

• Importance of women informing their clinician if they are or plan to become pregnant or to breast-feed.27

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.27

• Importance of informing patients of other important precautionary information.27 (See Cautions.)

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.

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.

Abuse: Abuse potential was not evaluated in human studies.

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.

Felbatol (Fel-ba-taal)

(felbamate)

Tablets and Oral Suspension

IS-00431-01                                      Rev. 7/11

Read 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 away
• Frequent infections or an infection that does not go away
• Easy bruising
• Red or purple spots on your body
• Bleeding gums or nose bleeds
• Severe fatigue or weakness

2. 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 urine
• nausea or vomiting
• loss of appetite
• pain 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 dying
• attempts to commit suicide
• new or worse depression
• new or worse anxiety
• feeling agitated or restless
• panic attacks
• trouble sleeping (insomnia)
• new or worse irritability
• acting aggressive, being angry, or violent
• acting on dangerous impulses
• an extreme increase in activity and talking (mania)
• other unusual changes in behavior or mood

How 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 generalization
• children with other medicines to treat:
  • seizures associated with Lennox-Gastaut syndrome

Who 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 problems
• have or have had liver problems

What should I tell my healthcare provider before taking Felbatol?

Before you take Felbatol, tell your healthcare provider if you:

• have kidney problems
• have or have had depression, mood problems, or suicidal thoughts or behavior
• have any other medical conditions
• are 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 loss
• vomiting
• trouble sleeping
• nausea
• dizziness
• sleepiness
• headache
• double-vision
• changes in the way that food tastes

These 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: felbamate

Tablet 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 7/11

MEDA Pharmaceuticals Inc., Somerset, NJ 08873-4120

Felbatol is a registered trademark of Meda Pharmaceuticals Inc.

IS-00431-01                          Rx Only                          Rev. 7/11