Felbamate

>10%

Adjunctive therapy

• Nausea (34.2%)
• Vomiting (16.7%)
• Constipation (11.4%)
• Dyspepsia (12.3%)
• Anorexia (19.3%)
• Dyspepsia (12.3%)

Lennox-Gastaut

• Anorexia (55%)
• Somnolence (48%)
• URI (46-50%)
• Vomiting (39%)
• Nervousness (16-20%)
• Insomnia (16.1%)
• Purpura (11-15%)
• Fever (22.6%)
• Constipation (12.9%)

1-10%

Monotherapy

• Acne (3.4%)
• Anxiety (5.2%)
• Constipation (6.9%)
• Diarrhea (5.2%)
• Diplopia (3.4%)
• Dyspepsia (8.6%)
• Face edema (3.4%)
• Fatigue (6.9%)
• Headache (6.9%)
• Insomnia (8.6%)
• Intramenstrual bleeding (3.4%)
• Otitis media (3.4%)
• Rash (3.4%)
• Urinary tract infection (3.4%)
• Vomiting (8.6%)

Adjunctive therapy

• Abdominal pain (5.3%)
• Abnormal gait (5.3%)
• Anxiety (5.3%)
• Ataxia (3.5%)
• Depression (5.3%)
• Increased ALT (3.5%)
• Diarrhea (5.3%)
• Dry mouth (2.6%)
• Diplopia (6-10%)
• Paresthesia (3.5%)
• Pharyngitis (2.6%)
• Stupor (2.6%)
• Sinusitis (2-5%)
• Tremor (6.1%)
• Upper respiratory infection (5.3%)

Lennox-Gastaut

• Abnormal gait (9.7%)
• Abnormal thoughts (6.5%)
• Ataxia (6.5%)
• Dyspepsia (6.5%)
• Emotional lability (6.5%)
• Fatigue (9.7%)
• Headache (6.5%)
• Hiccup (9.7%)
• Leukopenia (6.5%)
• Miosis (6.5%)
• Nausea (6.5%)
• Coughing (6.5%)
• Pain (6.5%)
• Pharyngitis (9.7%)
• Otitis media (6-10%)

<1%

Atrial arrhythmia

Bradycardia

Hypotension

Thrombophlebitis

Cerebral edema

Coma

Alopecia

Jaundice

Hepatic failure

Rigors

Rhabdomyolysis

Pregnancy Category: C

Lactation: Excreted in milk; not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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.sov/medwatch.

MEDA Pharmaceuticals Inc. Somerset, NJ 08873. Rev. 7/11

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 14C 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

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® (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.

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®.

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.

Felbamate is an anti-epileptic medication, also called an anticonvulsant.

Felbamate is used alone or in combination with other medications to treat seizures in adults with epilepsy. Felbamate is also used to treat children with Lennox-Gastaut syndrome, a severe form of childhood epilepsy that also causes developmental and behavior problems.

Felbamate is usually given after other seizure medications have been tried without successful treatment of symptoms.

Felbamate may also be used for purposes not listed in this medication guide.

Felbamate can cause serious side effects and is usually given only to people with severe epilepsy when the need for seizure control outweighs the risk of side effects. You may be asked to sign a consent form after you and your doctor have discussed the risks and benefits of taking felbamate.

You should not use this medication if you are allergic to felbamate, or if you have liver disease or a history of blood cell disorders such as anemia.

To make sure felbamate is safe for you, tell your doctor if you have kidney disease.

You may have thoughts about suicide while taking this medicine. Tell your doctor if you have depression or suicidal thoughts during the first several weeks of treatment, or whenever your dose is changed.

Your family or other caregivers should also be alert to changes in your mood or symptoms. Your doctor will need to check you at regular visits.

FDA pregnancy category C. It is not known whether felbamate will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Felbamate can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Your pharmacist can provide more information about felbamate.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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Felbamate can cause a decrease in many types of blood cells (white cells, red cells, platelets). Call your doctor at once if you have any unusual bleeding, weakness, or any signs of infection, even if these symptoms first occur after you have been using the medication for several months.

Felbamate may also cause liver damage. Call your doctor if you have symptoms such as nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

You may have thoughts about suicide when you first start taking this medicine. Your doctor will need to check you at regular visits.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), depressed, or have thoughts about suicide or hurting yourself.

Do not stop using felbamate without first talking to your doctor, even if you feel fine. You may have increased seizures if you stop using felbamate suddenly. You may need to use less and less before you stop the medication completely.

Contact your doctor if your seizures get worse or you have them more often while taking felbamate.

Wear a medical alert tag or carry an ID card stating that you take felbamate. Any medical care provider who treats you should know that you take seizure medication.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include fast heart rate, upset stomach, or unusual thoughts or behaviors.

Tell your doctor about all other medicines you use, especially other seizure medications, such as:

• carbamazepine (Carbatrol, Equetro, Tegretol);

• clopidogrel (Plavix);

• divalproex (Depakote);

• oxcarbazepine (Trileptal);

• phenobarbital (Solfoton);

• phenytoin (Dilantin); or

• valproic acid (Depakene, Stavzor).

This list is not complete and other drugs may interact with felbamate. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

General

• Prior to initiation of therapy, discuss the risks associated with use of felbamate with the patient, parent, or guardian and obtain written informed consent.27 32

• Obtain expert hematologic consultation prior to initiation of therapy and whenever any hematologic abnormality is detected during the course of therapy.19 27

• Closely monitor for notable changes in behavior that could indicate emergence or worsening of suicidal thoughts or behavior or depression.35 36 37 39 (See Suicidality Risk under Cautions.)

• Abrupt withdrawal may result in increased seizure frequency;1 withdraw gradually and reduce dosage slowly.27 (See Withdrawal Seizures under Cautions.)

Administration

Oral Administration

Administer orally in 3 or 4 divided doses without regard to meals.27

Administer orally in 3 or 4 divided doses;27 effect of food on absorption of the suspension has not been evaluated.27 Shake well before administration.27

Dosage

When adding to an existing anticonvulsant regimen, add gradually while reducing the dosage(s) of other anticonvulsant(s).1 (See Specific Drugs under Interactions.)

Pediatric Patients

Children 2–14 years of age: Initially, 15 mg/kg daily administered in 3 or 4 divided doses.1 15 Dosage may be increased by 15 mg/kg daily at weekly intervals to a maximum dosage of 45 mg/kg daily administered in 3 or 4 divided doses.1 15

As felbamate is added to the anticonvulsant regimen, the dosage(s) of other anticonvulsant(s) must be gradually decreased, initially by at least 20%;1 15 19 further reductions in dosage(s) of concomitant anticonvulsant(s) may be necessary as felbamate dosage is increased.1 19

Adolescents ≥14 years of age should receive dosages recommended for adults.1 (See Adults under Dosage and Administration.)

Adults

Initially, 1.2 g daily administered in 3 or 4 divided doses.1 Titrate previously untreated patients under close clinical supervision, increasing dosage in 600-mg daily increments every 2 weeks to 2.4 g daily based on clinical response and thereafter to 3.6 g daily if clinically indicated.38 Felbamate has not been evaluated systematically as initial monotherapy.1

Initially, 1.2 g daily administered in 3 or 4 divided doses.1 At the same time, reduce the dosage(s) of concomitantly administered anticonvulsant(s) by 33%.38 At week 2, increase the felbamate dosage to 2.4 g daily while reducing the dosage(s) of other anticonvulsant(s) by up to an additional 33% of their baseline dosage(s).38 At week 3, increase the felbamate dosage to 3.6 g daily and continue to reduce the dosage(s) of other anticonvulsant(s) as clinically indicated.38

Initially, 1.2 g daily administered in 3 or 4 divided doses.1 Dosage may be increased by 1.2-g daily increments at weekly intervals to a maximum of 3.6 g daily administered in 3 or 4 divided doses.1

As felbamate is added to the anticonvulsant regimen, the dosage(s) of other anticonvulsant(s) must be gradually decreased, initially by at least 20%;1 15 19 further reductions in dosage(s) of concomitant anticonvulsant(s) may be necessary as felbamate dosage is increased.1 19

More rapid titration of felbamate dosage (e.g., increasing dosage to 3.6 g daily over a 3-day period) occasionally has been employed.1 8 11 14

Prescribing Limits

Pediatric Patients

Children 2–14 years of age: Maximum 45 mg/kg daily.1 15

Adolescents ≥14 years of age: Maximum 3.6 g daily.1 8 11 14

Adults

Maximum 3.6 g daily.1 8 11 14

Special Populations

Renal Impairment

Reduce initial and maintenance dosages by 50%.38 Adjunctive therapy with drugs that affect plasma felbamate concentrations, especially other anticonvulsants, may warrant further reductions in felbamate daily dosage in patients with renal dysfunction.38

• Structurally related to but pharmacologically distinct from meprobamate, an anxiolytic agent.3 5 7 20

• Exact mechanism of action of anticonvulsant effect not known, but available data suggest that the drug increases seizure threshold and reduces seizure spread.1 4 6 20

• Exhibits a spectrum of anticonvulsant activity that is pharmacologically distinct from the spectra of other currently available agents.1 4 6 7 20

• Weak inhibitor in vitro at GABA receptors and benzodiazepine receptors.1

• 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.)

Felbamate is used alone or together with other medicines to control partial seizures (convulsions) in the treatment of epilepsy, after other therapies have failed or are not right for the patient. It is also used in children to control partial and generalized seizures caused by Lennox-Gastaut syndrome.

Felbamate belongs to a class of medicines called anticonvulsants. It acts in the brain to prevent seizures. However, felbamate cannot cure epilepsy and will only work to control seizures for as long as you continue to take it.

felbamate is available only with your doctor's prescription.

It is very important that your doctor check the progress of you or your child at regular visits. This is necessary to allow dose adjustments and to check for serious unwanted effects.

It is important to tell your doctor if you become pregnant. Your doctor may want you to join the North American Antiepileptic Drug Pregnancy Registry, which is used by pregnant patients who are taking felbamate.

Felbamate has caused a few cases of a serious blood disorder called aplastic anemia and a few cases of liver failure. Talk to your doctor about these risks.

Stop using felbamate and check with your doctor right away if you or your child have pain or tenderness in the upper stomach; pale stools; dark urine; loss of appetite; nausea; unusual tiredness or weakness; or yellow eyes or skin. These could be symptoms of a serious liver problem.

Tell your doctor right away if you or your child has chest pain; chills; cough; fever; headache; shortness of breath; sores, ulcers, or white spots on lips or in mouth; swollen or painful glands; tightness in chest; unusual bleeding or bruising; unusual tiredness or weakness; or wheezing. These could be symptoms of aplastic anemia.

Do not stop taking felbamate without first checking with your doctor. Your doctor may want you to gradually reduce the amount you or your child are taking before stopping completely. Stopping the medicine suddenly may cause your seizures to return or to occur more often.

If you or your child develop any unusual or strange thoughts and behavior while taking felbamate, be sure to discuss it with your doctor. Other changes might be confusion, worsening of depression, hallucinations (seeing, hearing, or feeling things that are not there), suicidal thoughts, and unusual excitement, nervousness, or irritability.

Felbamate may cause blurred vision, double vision, or other changes in vision. It may also cause some people to become dizzy or drowsy. Make sure you know how you react to felbamate before you drive, use machines, or do anything else that could be dangerous if you are not alert or able to see well. If these reactions are especially bothersome, check with your doctor.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• chest pain
• chills
• confusion
• cough
• delusions
• dementia
• depression
• fever
• loss of bladder control
• painful or difficult urination
• purple or red spots on the skin
• shakiness in the legs, arms, hands, or feet
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• trembling or shaking of the hands or feet
• unusual bleeding or bruising
• unusual tiredness or weakness

• Agitation, aggression, or other mood or mental changes
• bladder pain
• bloody or cloudy urine
• bone pain
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• clumsiness or unsteadiness
• frequent urge to urinate
• loss of appetite
• lower back or side pain
• skin rash
• swelling or puffiness of the face
• trouble with breathing
• unsteadiness, trembling, or other problems with muscle control or coordination

• Continuing headache
• continuing stomach pain
• continuing vomiting
• dark-colored urine
• general feeling of tiredness or weakness
• hives or itching
• light-colored stools
• muscle cramps
• nasal congestion
• nosebleeds or other unusual bruising or bleeding
• pain
• sensitivity of the skin to sunlight
• swollen or painful glands
• tightness in the chest
• yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• bad, unusual, or unpleasant (after) taste
• belching
• body aches or pain
• change in taste
• change in walking and balance
• constricted, pinpoint, or small pupils (black part of the eye)
• crying
• depersonalization
• diarrhea
• difficulty having a bowel movement (stool)
• difficulty with sleeping
• dizziness
• double vision
• dysphoria
• ear congestion
• euphoria
• headache
• heartburn
• hiccup
• indigestion
• loss of appetite
• loss of voice
• nausea
• paranoia
• quick to react or overreact emotionally
• rapidly changing moods
• runny nose
• seeing double
• sleepiness or unusual drowsiness
• sleeplessness
• sneezing
• stomach discomfort, upset, or pain
• trouble sleeping
• unable to sleep
• weight loss

• Blemishes on the skin
• blurred vision
• decreased awareness or responsiveness
• decreased weight
• difficulty with moving
• earache
• hoarseness
• joint pain
• muscle aching or cramping
• muscle pains or stiffness
• pain or tenderness around the eyes and cheekbones
• pimples
• redness or swelling in the ear
• severe sleepiness
• swollen joints
• tender, swollen glands in the neck
• trouble with swallowing
• voice changes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Felbamate is an antiepileptic available as 400 mg and 600 mg tablets for oral administration. Its chemical name is 2-phenyl-1,3-propanediol dicarbamate.

Felbamate, USP is white to off-white powder. It is freely soluble in dimethyl sulfoxide, sparingly soluble in methanol, slightly soluble in acetonitrile and very slightly soluble in water.

Felbamate's molecular weight is 238.24, its molecular formula is C11H14N2O4 and its structural formula is:

Each Felbamate tablet, USP contains Felbamate, USP 400 mg or 600 mg and following inactive ingredients: colloidal silicon dioxide, ferric oxide yellow, FD & C red no. 40 aluminum lake, lactose monohydrate, microcrystalline cellulose, magnesium stearate, povidone K 30, pregelatinised starch (botanical source: corn) and sodium starch glycolate type A (botanical source: potato). Apart from this Felbamate tablets USP, 600 mg also contain D & C yellow no. 10 aluminum lake.

Felbamate

(fel-BAM-ate)

Felbamate Tablets, USP

Read this Medication Guide before you start taking Felbamate tablets 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 Felbamate tablets?

Do not stop taking Felbamate tablets without first talking to your healthcare provider.

Stopping Felbamate tablets suddenly can cause serious problems.

Felbamate tablets can cause serious side effects, including:

1. Felbamate tablets 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, Felbamate tablets 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 Felbamate tablets without first talking to a healthcare provider.

Stopping Felbamate tablets suddenly can cause serious problems. You should talk to your healthcare 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 are Felbamate tablets?

Felbamate tablets are 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 Felbamate tablets?

Do not take Felbamate tablets if you:

• are allergic to Felbamate, carbamates or any of the ingredients in Felbamate tablets. See the end of this Medication Guide for a complete list of ingredients in Felbamate tablets.
• have or have had blood problems
• have or have had liver problems

What should I tell my healthcare provider before taking Felbamate tablets?

Before you take Felbamate tablets, 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 Felbamate tablets can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking Felbamate tablets. You and your healthcare provider will decide if you should take Felbamate tablets while you are pregnant.
  • If you become pregnant while taking Felbamate tablets, 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. Felbamate may pass into your breast milk. You and your healthcare provider should decide if you should take Felbamate tablets while you breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Taking Felbamate tablets 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 Felbamate tablets?

• Take Felbamate exactly as your healthcare provider tells you. Your healthcare provider will tell you how much Felbamate to take and when to take it.
• Your healthcare provider may change your dose of Felbamate. Do not change your dose of Felbamate 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 Felbamate tablets.
• If you take too much Felbamate, call your healthcare provider or local Poison Control Center right away.
• Do not stop Felbamate tablets without first talking to your healthcare provider.

What should I avoid while taking Felbamate tablets?

• Felbamate tablets can cause drowsiness and dizziness. Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking Felbamate tablets, until you talk with your doctor. Taking Felbamate tablets with alcohol or drugs that cause sleepiness or dizziness may make your sleepiness or dizziness worse.

What are the possible side effects of Felbamate tablets?

See "What is the most important information I should know about Felbamate tablets?" Felbamate tablets may cause serious side effects including:

The most common side effects of Felbamate tablets 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 Felbamate tablets. 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 Felbamate tablets?

• Store Felbamate tablets between 68°F to 77°F (20°C to 25°C).

Keep Felbamate tablets and all medicines out of the reach of children.

General information about Felbamate tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Felbamate tablets for a condition for which it was not prescribed. Do not give Felbamate tablets 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 Felbamate tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Felbamate tablets that is written for health professionals.

What are the ingredients in Felbamate tablets?

Active Ingredient: Felbamate, USP

Inactive Ingredients: colloidal silicon dioxide, ferric oxide yellow, FD & C red no. 40 aluminum lake, lactose monohydrate, microcrystalline cellulose, magnesium stearate, povidone K 30, pregelatinised starch (botanical source: corn) and sodium starch glycolate type A (botanical source: potato). Apart from this Felbamate tablets USP, 600 mg also contain D & C yellow no. 10 aluminum lake.

Please address medical inquiries to, (MedicalAffairs@zydususa.com) Tel.: 1-877-993-8779.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Cadila Healthcare Limited

Matoda, Ahmedabad, India.

Distributed by:

Zydus Pharmaceuticals (USA) Inc.

Pennington, NJ 08534

Rev.: 06/17

Use caution; reduce initial and maintenance doses by 50%. Adjunctive therapy with medications that affect felbamate plasma concentrations, especially AEDs, may warrant further reductions in felbamate daily doses in patients with renal dysfunction.

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Aprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Barbiturates: Felbamate may increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Felbamate. Management: Monitor for elevated barbiturate concentrations/toxicity if felbamate is initiated/dose increased, or reduced concentrations/effects if felbamate is discontinued/dose decreased. Refer to phenobarbital dosing guidelines for patients receiving that agent. Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Felbamate. Felbamate may decrease the serum concentration of CarBAMazepine. Management: In patients receiving carbamazepine, initiate felbamate at 1200 mg/day in divided doses 3-4 times daily while reducing carbamazepine dose by 20%. Monitor for reduced concentrations/effects of both drugs. Consider therapy modification

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Contraceptives (Estrogens): Felbamate may decrease the serum concentration of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of a nonhormonal contraceptive is recommended. Consider therapy modification

Contraceptives (Progestins): Felbamate may decrease the serum concentration of Contraceptives (Progestins). Management: Contraceptive failure is possible. Use of an alternative, nonhormonal method of contraception is recommended. Consider therapy modification

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates. Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Felbamate. Felbamate may increase the serum concentration of Fosphenytoin. Management: Decreased phenytoin dose will likely be needed when adding felbamate; some reports suggest an empiric 20% decrease in phenytoin dose. Additional reductions may be needed if felbamate dose is increased or as otherwise guided by monitoring. Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates. Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

PHENobarbital: May decrease the serum concentration of Felbamate. Felbamate may increase the serum concentration of PHENobarbital. Management: In patients receiving phenobarbital, initiate felbamate at 1200 mg/day in divided doses 3-4 times daily and reduce phenobarbital dose by 20%. Monitor for increased phenobarbital concentrations/effects and decreased felbamate concentrations/effects. Consider therapy modification

Phenytoin: Felbamate may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Felbamate. Management: Decreased phenytoin dose will likely be needed when adding felbamate; some reports suggest an empiric 20% decrease in phenytoin dose. Additional reductions may be needed if felbamate dose is increased or as otherwise guided by monitoring. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Primidone: Felbamate may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations may increase. Primidone may decrease the serum concentration of Felbamate. Management: In patients receiving primidone, initiate felbamate at 1200 mg/day in divided doses 3-4 times daily and reduce primidone dose by 20%. Monitor for increased phenobarbital concentrations/effects and decreased felbamate concentrations/effects. Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates. Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ulipristal: Felbamate may decrease the serum concentration of Ulipristal. Avoid combination

Valproate Products: Felbamate may increase the serum concentration of Valproate Products. Consider therapy modification

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

>10%:

Central nervous system: Drowsiness (children: 48%; adults: 19%), headache (adults: 7% to 37%; children: 7%), dizziness (18%), insomnia (9% to 18%), fatigue (7% to 17%), nervousness (children: 16%; adults: 7%)

Gastrointestinal: Anorexia (children: 55%; adults: 19%), vomiting (children: 39%; adults: 9% to 17%), nausea (adults: 34%; children: 7%), dyspepsia (9% to 12%), constipation (7% to 11%)

Hematologic & oncologic: Purpura (children: 13%)

Respiratory: Upper respiratory infection (children: 45%; adults: 5% to 9%)

Miscellaneous: Fever (children: 23%; adults: 3%)

1% to 10%:

Cardiovascular: Chest pain (3%), facial edema (3%), palpitations (≥1%), tachycardia (≥1%)

Central nervous system: Abnormal gait (children: 10%; adults: 5%), abnormality in thinking (children: 7%), ataxia (children: 7%; adults: 4%), emotional lability (children: 7%), pain (children: 7%), anxiety (5%), depression (5%), paresthesia (4%), stupor (3%), aggressive behavior (≥1%), agitation (≥1%), malaise (≥1%), psychological disorder (≥1%), attempted suicide (≤1%), dystonia (≤1%), euphoria (≤1%), hallucination (≤1%), migraine (≤1%)

Dermatologic: Skin rash (children: 10%; adults: 3% to 4%), acne vulgaris (3%), pruritus (≥1%), bullous rash (≤1%), urticaria (≤1%)

Endocrine and metabolic: Menstrual disease (3%), hypophosphatemia (≤3%), hypokalemia (≤1%), hyponatremia (≤1%), increased lactate dehydrogenase (≤1%)

Gastrointestinal: Hiccups (children: 10%), weight loss (children: 7%; adults: 3%), dysgeusia (6%), abdominal pain (5%), diarrhea (5%), xerostomia (3%), weight gain (≥1%), esophagitis (≤1%), increased appetite (≤1%)

Genitourinary: Urinary tract infection (3%)

Hematologic & oncologic: Leukopenia (children: 7%; adults: ≤1%), granulocytopenia (≤1%), leukocytosis (≤1%), lymphadenopathy (≤1%), thrombocytopenia (≤1%)

Hepatic: Increased liver enzymes (1% to 5%), increased serum alkaline phosphatase (≤1%)

Neuromuscular & skeletal: Tremor (6%), myalgia (3%), weakness (≥1%)

Ophthalmic: Miosis (children: 7%), diplopia (3% to 6%), visual disturbance (5%)

Otic: Otitis media (children: 10%; adults: 3%)

Respiratory: Pharyngitis (children: 10%; adults: 3%), cough (children: 7%), rhinitis (7%), sinusitis (4%), flu-like symptoms (≥1%)

<1% (Limited to important or life-threatening): Acute renal failure, agranulocytosis, alopecia, anaphylactoid reaction, anemia, apathy, aphthous stomatitis, aplastic anemia, atrial arrhythmia, atrial fibrillation, blood coagulation disorder, blood platelet disorder, body odor, bradycardia, brain disease, buccal mucous membrane swelling, cardiac failure, cerebral edema, cerebrovascular disease, choreoathetosis, coma, confusion, delusions, diaphoresis, disseminated intravascular coagulation (DIC), dysarthria, dyskinesia, dysphagia, dyspnea, dysuria, embolism, enteritis, eosinophilia, epistaxis, exacerbation of asthma, extrapyramidal reaction, flatulence, flushing, gastric ulcer, gastritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, gingival hemorrhage, glossitis, hematemesis, hematuria, hemianopia, hemolytic anemia, hepatic failure, hepatitis, hepatorenal syndrome, hyperammonemia, hyperglycemia, hypernatremia, hypersensitivity reaction, hypertension, hypocalcemia, hypoglycemia, hypomagnesemia, hypotension, hypoxia, IgA vasculitis, increased creatine phosphokinase, intestinal obstruction, jaundice, lack of concentration, leukemia, lichen planus, livedo reticularis, manic reaction, nephrosis, neuritis (mononeuritis), nystagmus, pancreatitis, pancytopenia, paralysis, paranoia, peripheral ischemia (potentially leading to necrosis), pleural effusion, pneumonitis, psychosis, pulmonary hemorrhage, rectal hemorrhage, renal insufficiency, respiratory depression, rhabdomyolysis, SIADH (syndrome of inappropriate antidiuretic hormone secretion), skin photosensitivity, status epilepticus, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies, supraventricular tachycardia, thrombophlebitis, torsades de pointes, toxic epidermal necrolysis, urinary retention, urticaria, vaginal hemorrhage

Commonly reported side effects of felbamate include: headache, nausea, vomiting, constipation, insomnia, and anorexia. Other side effects include: abdominal pain, abnormal gait, depression, diplopia, nervousness, tremor, and dysgeusia. See below for a comprehensive list of adverse effects.

Use with caution.