Drugs Details

Drugs Info of Felbatol
Drugs Details
  • Drugs Type  : Multum
  • Date : 28th Jan 2015 03:58 am
  • Brand Name : Felbatol
  • Generic Name : felbamate (Pronunciation: fel BAM ate)
Descriptions

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-l,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 C11H14N2O4; its structural formula is:

 

FELBATOL®
  (felbamate) Structural Formula Illustration

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.

What are the possible side effects of felbamate (Felbatol)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; fever; swollen glands; painful sores in or around your eyes or mouth; difficulty breathing; swelling of your face, lips, tongue, or throat.

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.

Call your doctor at once if you have any...

Read All Potential Side Effects and See Pictures of Felbatol »

What are the precautions when taking felbamate (Felbatol)?

Before taking felbamate, tell your doctor or pharmacist if you are allergic to it; or to meprobamate; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: blood problems (e.g., anemia), liver disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid...

Read All Potential Precautions of Felbatol »

This monograph has been modified to include the generic and brand name in many instances.

Indications

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.

Dosage 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)

  WEEK1 WEEK 2 WEEK 3
Dosage reduction of concomitant AEDs REDUCE original dose by 20-33%* REDUCE original dose by up to an additional 1/3* REDUCE as clinically indicated
Felbatol® Dosage 1200 mg/day Initial dose 2400 mg/day Therapeutic dosage range 3600 mg/day Therapeutic dosage range
*See Adjunctive and Conversion to Monotherapy sections.

While 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.sov/medwatch.

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

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

To report SUSPECTED ADVERSE REACTIONS, contact Meda Pharmaceuticals Inc. at 1-800-526-3840 or FDA at 1-800-FDA-1088 or www.fda.eov/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.

Adults
Incidence 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

  Felbatol®*
(N=58)
Low Dose Valproate**
(N=50)
Body System Event % %
Body as a Whole
  Fatigue 6.9 4.0
  Weight Decrease 3.4 0
  Face Edema 3.4 0
Central Nervous System
  Insomnia 8.6 4.0
  Headache 6.9 18.0
  Anxiety 5.2 2.0
Dermatological
  Acne 3.4 0
  Rash 3.4 0
Digestive
  Dyspepsia 8.6 2.0
  Vomiting 8.6 2.0
  Constipation 6.9 2.0
  Diarrhea 5.2 0
  SGPT Increased 5.2 2.0
Metabolic/Nutritional
  Hypophosphatemia 3.4 0
Respiratory
  Upper Respiratory Tract Infection 8.6 4.0
  Rhinitis 6.9 0
Special Senses
  Diplopia 3.4 4.0
  Otitis Media 3.4 0
Urogenital
  Intramenstrual Bleeding 3.4 0
  Urinary Tract Infection 3.4 2.0
*3600 mg/day;
** 15 mg/kg/day
Incidence 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

Body System/Event Felbatol® Placebo
(N=114) (N=43)
% %
Body as a Whole
  Fatigue 16.8 7.0
  Fever 2.6 4.7
  Chest Pain 2.6 0
Central Nervous System
  Headache 36.8 9.3
  Somnolence 19.3 7.0
  Dizziness 18.4 14.0
  Insomnia 17.5 7.0
  Nervousness 7.0 2.3
  Tremor 6.1 2.3
  Anxiety 5.3 4.7
  Gait Abnormal 5.3 0
  Depression 5.3 0
  Paraesthesia 3.5 2.3
  Ataxia 3.5 0
  Mouth Dry 2.6 0
  Stupor 2.6 0
Dermatological
  Rash 3.5 4.7
Digestive
  Nausea 34.2 2.3
  Anorexia 19.3 2.3
  Vomiting 16.7 4.7
  Dyspepsia 12.3 7.0
  Constipation 11.4 2.3
  Diarrhea 5.3 2.3
  Abdominal Pain 5.3 0
  SGPT Increased 3.5 0
Musculoskeletal
  Myalgia 2.6 0
Respiratory
  Upper Respiratory Tract Infection 5.3 7.0
  Sinusitis 3.5 0
  Pharyngitis 2.6 0
Special Senses
  Diplopia 6.1 0
  Taste Perversion 6.1 0
  Vision Abnormal 5.3 2.3
Children
Incidence 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

Body System/Event Felbatol® Placebo
(N=31) (N=27)
% %
Body as a Whole
  Fever 22.6 11.1
  Fatigue 9.7 3.7
  Weight Decrease 6.5 0
  Pain 6.5 0
Central Nervous System
  Somnolence 48.4 11.1
  Insomnia 16.1 14.8
  Nervousness 16.1 18.5
  Gait Abnormal 9.7 0
  Headache 6.5 18.5
  Thinking Abnormal 6.5 3.7
  Ataxia 6.5 3.7
  Urinary Incontinence 6.5 7.4
  Emotional Lability 6.5 0
  Miosis 6.5 0
Dermatological
  Rash 9.7 7.4
Digestive
  Anorexia 54.8 14.8
  Vomiting 38.7 14.8
  Constipation 12.9 0
  Hiccup 9.7 3.7
  Nausea 6.5 0
  Dyspepsia 6.5 3.7
Hematologic
  Purpura 12.9 7.4
  Leukopenia 6.5 0
Respiratory
  Upper Respiratory Tract Infection 45.2 25.9
  Pharyngitis 9.7 3.7
  Coughing 6.5 0
Special Senses
  Otitis Media 9.7 0

Other 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: GOT 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-Schonlein 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.

Drug Abuse And Dependence

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.

Read the Felbatol (felbamate) Side Effects Center for a complete guide to possible side effects

Learn More »

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

AED
Coadministered
AED
Concentration
Felbatol®
Concentration
Phenytoin
Valproate ↔**
Carbamazepine (CBZ)
*CBZ epoxide

Phenobarbital
*Not administered but an active metabolite of carbamazepine.
**No significant effect.

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 ofFelbatol® 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 ofFelbatol®, respectively. This indicates that the protein binding of valproate did not change appreciably with increasing doses ofFelbatol®.

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 ofFelbatol® (felbamate) at steady-state and, therefore, the addition of phenytoin causes an approximate 45% decrease in the steady-state trough concentrations ofFelbatol® as compared to the same dose ofFelbatol® 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/Laboratory Test Interactions

There are no known interactions of Felbatol® with commonly used laboratory tests.

Read the Felbatol Drug Interactions Center for a complete guide to possible interactions

Learn More »

This monograph has been modified to include the generic and brand name in many instances.

Warnings

See BOXED WARNINGS 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 Analysis

Indication Placebo Patients with Events
Per 1000 Patients
Drug Patients with Events
Per 1000 Patients
Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug
Patients with Events Per 1000 Patients
Epilepsy 1.0 3.4 3.5 2.4
Psychiatric 5.7 8.5 1.5 2.9
Other 1.0 1.8 1.9 0.9
Total 2.4 4.3 1.8 1.9

The 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.

Precautions

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).

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 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/m2 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/m2 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 and Delivery

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

Nursing Mothers

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

Pediatric Use

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

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.

This monograph has been modified to include the generic and brand name in many instances.

OverDose

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.

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.

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

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

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.

This monograph has been modified to include the generic and brand name in many instances.

Patient Information

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

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 BOXED 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).

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 safely of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see Pregnancy section).

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:

1.1,____________________________________________________________(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:_________________________

2.1 understand that Felbatol® is being used because my seizures have not been satisfactorily treated with other antiepileptic drugs;

INITIALS:_________________________

3.1 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:_________________________

4.1 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:_________________________

5.1 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:_________________________

7.1 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:_________________________

8.1 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

Telephone

PHYSICIAN 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 ................ Date ..............

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.

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This 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 for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

FELBAMATE - ORAL

 

(fel-BAM-ate)

 

COMMON BRAND NAME(S): Felbatol

 

WARNING: Severe (sometimes fatal) blood disorders (aplastic anemia, pancytopenia) and liver problems have occurred with felbamate. Felbamate should be used only in people with severe seizures (epilepsy) that cannot be controlled with other medications. This drug should not be used if you have liver problems. Discuss the risks and benefits with your doctor before starting felbamate.

Immediately tell your doctor if you have symptoms of infection (fever, chills, persistent sore throat), anemia (tiredness, pale skin/fingernails, fast heartbeat), liver problems (e.g., severe stomach/abdominal pain, unusual weakness/tiredness, pale stools, dark urine, yellowing eyes/skin) or if you have unusual bleeding/bruising. Usually, people who have liver problems while taking this drug should not start taking it again.

Your doctor will perform certain blood tests (e.g., liver function, complete blood count) and may have you see a doctor who treats blood problems (hematologist) before you start felbamate and while you use this drug. Aplastic anemia may occur after you stop taking the drug. Therefore, blood tests may be needed for some time after you stop taking it. Keep all medical/laboratory appointments.

 

USES: This medication is used alone or with other medications to treat severe seizures (epilepsy). This medication should be used only when you cannot take other medications or when other medications have not been able to control your seizures.

 

HOW TO USE: Read the Medication Guide provided by your pharmacist. Read and sign the Informed Consent form provided by your doctor. If you have any questions, ask your doctor or pharmacist before starting felbamate.

Take this medication with or without food, usually 3-4 times a day or as directed by your doctor. Take with food or milk if stomach upset occurs. Follow the dosing schedule carefully.

If you are using the liquid form of this medication, shake the container well before pouring each dose. Measure the dose carefully using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.

The dosage is based on your medical condition and response to therapy. Your doctor may direct you to take a low dose at first, gradually increasing the dose to lower the chance of side effects such as upset stomach and drowsiness. Your doctor will adjust your dose to find the best dose for you. Follow your doctor's directions carefully. The usual maximum dose for adults is 3600 milligrams each day.

Take this medication regularly in order to get the most benefit from it. To help you remember, take it at the same times each day. Do not skip doses.

If you are already taking another anti-seizure drug, follow your doctor's directions carefully for stopping or continuing the old drug and starting felbamate.

Do not stop taking this medication or any anti-seizure medication without consulting your doctor. Your seizures may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.

Inform your doctor if your condition persists or worsens.

Consumer Overview Side Effect

SIDE EFFECTS: See also Warning section.

Drowsiness, dizziness, nausea, vomiting, diarrhea, trouble sleeping, loss of coordination, headache, hiccups, and loss of appetite may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: ear pain, vision changes (e.g., blurred vision, double vision).

A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor immediately if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.

Tell your doctor immediately if any of these rare but very serious side effects occur: fast/irregular/pounding heartbeat, fainting.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

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

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Felbatol (felbamate) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before taking felbamate, tell your doctor or pharmacist if you are allergic to it; or to meprobamate; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: blood problems (e.g., anemia), liver disease.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Avoid alcoholic beverages.

Older adults may be more sensitive to the side effects of this drug, especially dizziness, loss of coordination, or fainting. These side effects can increase the risk of falling.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: other anti-seizure medications (e.g., phenytoin, valproate).

This medication may decrease the effectiveness of hormonal birth control such as pills, patch, or ring. This could cause pregnancy. Discuss with your doctor or pharmacist if you should use additional reliable birth control methods while using this medication. Also tell your doctor if you have any new spotting or breakthrough bleeding, because these may be signs that your birth control is not working well.

Also report the use of drugs which might increase seizure risk such as isoniazid (INH), phenothiazines (e.g., thioridazine), theophylline, or tricyclic antidepressants (e.g., amitriptyline), among others. Consult your doctor or pharmacist for details.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, amitriptyline, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood count, kidney/liver tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised December 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Felbatol

Generic Name: felbamate (Pronunciation: fel BAM ate)

  • What is felbamate (Felbatol)?
  • What are the possible side effects of felbamate (Felbatol)?
  • What is the most important information I should know about felbamate (Felbatol)?
  • What should I discuss with my healthcare provider before taking felbamate (Felbatol)?
  • How should I take felbamate (Felbatol)?
  • What happens if I miss a dose (Felbatol)?
  • What happens if I overdose (Felbatol)?
  • What should I avoid while taking felbamate (Felbatol)?
  • What other drugs will affect felbamate (Felbatol)?
  • Where can I get more information?

What is felbamate (Felbatol)?

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 400 mg-AMN

oval, yellow, imprinted with AN 734

What are the possible side effects of felbamate (Felbatol)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; fever; swollen glands; painful sores in or around your eyes or mouth; difficulty breathing; swelling of your face, lips, tongue, or throat.

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.

Call your doctor at once if you have any of these serious side effects:

  • pale skin, weakness, easy bruising or bleeding (nosebleeds, bleeding gums);
  • fever, chills, body aches, flu symptoms;
  • fast or pounding heartbeats, feeling short of breath;
  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • pain or burning when you urinate;
  • loss of balance or coordination; or
  • worsening of seizures.

Less serious side effects may include:

  • dizziness, drowsiness, nervousness, tired feeling;
  • headache;
  • sleep problems (insomnia);
  • changes in weight or appetite;
  • acne, mild itching or skin rash;
  • diarrhea, constipation, vomiting;
  • runny or stuffy nose;
  • blurred vision; or
  • changes in your sense of taste.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Felbatol (felbamate) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about felbamate (Felbatol)?

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.

Side Effects Centers
  • Felbatol

Patient Detailed How Take

What should I discuss with my healthcare provider before taking felbamate (Felbatol)?

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.

How should I take felbamate (Felbatol)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

If you are switching to felbamate from another anticonvulsant medication, carefully follow your doctor's instructions about timing and dosage when switching from one drug to another. Your doctor may occasionally change your dose over several weeks or months to make sure you get the best results from this medication.

Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Felbamate can cause a decrease in many types of blood cells (white cells, red cells, platelets). This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Call your doctor at once if you have any unusual bleeding, weakness, or any signs of infection, including flu-like symptoms. These symptoms may first develop even after you have been using the medication for several months.

You may need regular medical tests to be sure this medication is not causing harmful effects. Visit your doctor regularly.

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.

Use felbamate regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

Store at room temperature away from moisture and heat.

Side Effects Centers
  • Felbatol

Patient Detailed Avoid Taking

What happens if I miss a dose (Felbatol)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Felbatol)?

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.

What should I avoid while taking felbamate (Felbatol)?

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

What other drugs will affect felbamate (Felbatol)?

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.

Where can I get more information?

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.

Copyright 1996-2013 Cerner Multum, Inc. Version: 6.01. Revision date: 9/28/2012.

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