Felbamate is an orally available medicine used to treat partial seizures in adults and generalized seizures associated with Lennox-Gastaut Syndrome in children.

Felbamate Uses:

• Partial seizures (monotherapy or adjunctive):

  • felbamate is used as a monotherapy or adjunctive therapy in the treatment of partial seizures (with and without generalization) in adults and adolescents 14 years and older.

• Lennox-Gastaut syndrome:

  • It is used as adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome in children
  • Limitations of use: Not indicated for use as first-line treatment for Lennox-Gastaut Syndrome.

Felbamate Dose in Adults

Felbamate Dose in the monotherapy of Partial seizures:

• Initial: 1,200 mg/day orally in 3 to 4 divided doses.
• Titrate previously untreated patients under close clinical supervision, increasing the dosage in 600 mg increments every 2 weeks to 2400 mg/day based on the clinical response of patients and thereafter to 3,600 mg/day if clinically indicated.

• Conversion to monotherapy:

  • Initiate at 1,200 mg/day in 3 to 4 divided doses
  • Reduce the dosage of the concomitant anticonvulsant(s) by 33% at the initiation of felbamate therapy.
  • At week 2, increase the felbamate dosage to 2,400 mg/day while reducing the dosage of the other anticonvulsant(s) up to an additional 33% of their original dosage.
  • At week 3, increase the felbamate dosage up to 3,600 mg/day and continue to reduce the dose of the other anticonvulsant(s) as clinically indicated.

Felbamate Dose in the adjunctive therapy of partial seizures:

• Oral: Initial: 1,200 mg/day in 3 to 4 divided doses; increase once per week by 1,200 mg/day increments up to 3,600 mg/day in 3 to 4 divided doses.

Note: Decrease the dosage of concomitant carbamazepine (and carbamazepine metabolites), phenytoin, phenobarbital, or valproic acid by 20% when initiating felbamate therapy. Further dosage reductions may be necessary as the dose of felbamate is increased.

Felbamate Dose in Childrens

Felbamate Dose as Anticonvulsant (adjunctive therapy):

• Adolescents ≥14 years:

  • Oral: Initial: 1,200 mg/day in 3 or 4 divided doses
  • Increase the dose in 1,200 mg/day increments at weekly intervals.
  • The maximum daily dose: 3,600 mg/day.
  • Note: At the initiation of felbamate therapy, decrease the dose of concomitant carbamazepine, phenytoin, phenobarbital, or valproic acid by 20%. Further dosage reductions may be necessary as the dose of felbamate is increased.

Felbamate Dose as Anticonvulsant (Monotherapy):

• Adolescents ≥ 14 years: Oral:

  • Initial: 1,200 mg/day in divided doses 3 or 4 times daily.
  • Titrate previously untreated patients under close clinical supervision, increasing the dose in 600 mg/day increments every 2 weeks to 2,400 mg/day based on clinical response and thereafter to 3,600 mg/day if clinically indicated.

• Conversion to monotherapy:

  • Initial: 1,200 mg/day in divided doses 3 or 4 times daily, reduce the dosage of the concomitant anticonvulsant(s) by 33% at the initiation of felbamate therapy;
  • At week 2, increase felbamate daily dose to 2000 mg/day in 3-4 divided doses while reducing the dosage of the other anticonvulsant(s) up to an additional 33% of their original dose.
  • At week 3, increase the felbamate dosage up to a maximum daily dose: 3,600 mg/day and continue to reduce the dosage of the other anticonvulsant(s) as clinically indicated.

Felbamate Dose in the adjunctive therapy of Lennox-Gastaut syndrome:

• Children and Adolescents 2 to 14 years:

  • Oral: Initial dose: 15 mg/kg/day in 3 or 4 divided doses.
  • Increase dose of felbamate by 15 mg/kg/day increments at weekly intervals.
  • The maximum daily dose: 45 mg/kg/day or 3,600 mg/day or whichever is less.

Note: At the initiation of felbamate, decrease the dose of concomitant carbamazepine, phenytoin, phenobarbital, or valproic acid by 20%. Further dosage reductions may be necessary as the dose of felbamate is increased.

Felbamate Pregnancy Risk Factor C

• Negative events have been reported in animal reproduction studies.
• Human postmarketing cases include anencephaly and encephalocele, placental disorder and fetal deaths.
• Further information can be found at www.aedpregnancyregistry.org.

Use of Felbamate during breastfeeding:

• Breast milk contains Felbamate.
• Breast-feeding is not recommended until more data are available.

Felbamate Dose in Kidney Disease:

• Use caution.
• Reduce initial and maintenance dosages by 50%.
• Adjunctive therapy with medications that affect felbamate plasma concentrations i.e AEDs, may warrant further reductions in felbamate daily doses in patients with renal dysfunction.

Felbamate Dose in Liver disease:

• Use is contraindicated in patients with a history of hepatic dysfunction.

Common Side Effects of Felbamate:

• Central Nervous System:

  • Drowsiness
  • Headache
  • Dizziness
  • Insomnia
  • Fatigue
  • Nervousness

• Gastrointestinal:

  • Anorexia
  • Vomiting
  • Nausea
  • Dyspepsia
  • Constipation

• Hematologic & Oncologic:

  • Purpura

• Respiratory:

  • Upper Respiratory Infection

• Miscellaneous:

  • Fever

Less Common Side Effects Of Felbamate:

• Cardiovascular:

  • Chest Pain
  • Facial Edema
  • Palpitations
  • Tachycardia

• Central Nervous System:

  • Abnormal Gait
  • Abnormality In Thinking
  • Ataxia
  • Emotional Lability
  • Pain
  • Anxiety
  • Depression
  • Paresthesia
  • Stupor
  • Aggressive Behavior
  • Agitation
  • Malaise
  • Psychological Disorder
  • Attempted Suicide
  • Dystonia
  • Euphoria
  • Hallucination
  • Migraine

• Dermatologic:

  • Skin Rash
  • Acne Vulgaris
  • Pruritus
  • Bullous Rash
  • Urticaria

• Endocrine And Metabolic:

  • Menstrual Disease
  • Hypophosphatemia
  • Hypokalemia
  • Hyponatremia
  • Increased Lactate Dehydrogenase

• Gastrointestinal:

  • Hiccups
  • Weight Loss
  • Dysgeusia
  • Abdominal Pain
  • Diarrhea
  • Xerostomia
  • Weight Gain
  • Esophagitis
  • Increased Appetite

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Leukopenia
  • Granulocytopenia
  • Leukocytosis
  • Lymphadenopathy
  • Thrombocytopenia

• Hepatic:

  • Increased Liver Enzymes
  • Increased Serum Alkaline Phosphatase

• Neuromuscular & Skeletal:

  • Tremor
  • Myalgia
  • Weakness

• Ophthalmic:

  • Miosis
  • Diplopia
  • Visual Disturbance

• Otic:

  • Otitis Media

• Respiratory:

  • Pharyngitis
  • Cough
  • Rhinitis
  • Sinusitis
  • Flu-Like Symptoms

Contraindications to Felbamate:

• Hypersensitivity to felbamate
• Hypersensitivity to carbamates or any other component of the formulation
• Any history of blood dyscrasia.
• Hepatic dysfunction

Warnings and precautions

• Aplastic anemia: [US-Boxed Warning]

  • A significantly higher risk of anemia is associated with Felbamate.
  • Aplastic anemia can be up to 100 times more common in patients who have not been treated.
  • Current fatality rates are between 20% and 30%. However, higher rates (upto 70%) have been reported in past years.
  • Fetal anemia can occur at any time during felbamate therapy, and even after the therapy has ended.
  • It is unknown if the dose, duration, and concomitant use of medication affect risk.
  • Routine blood monitoring can be useful in detecting hematologic signs and symptoms before they become clinically apparent.
  • However, aplasticanemia often occurs without warning or indication.
  • If you notice evidence of bone-marrow suppression, discontinue using the medication.

• Hepatic failure: [US Boxed Warning]

  • Rare cases of hepatic dysfunction have been linked to Felbamate (estimated at >6 cases per 75,000 patients annually).
  • 67% of the cases described in the literature have led to liver transplantation or death.
  • Prodromal symptoms may be present before the onset of hepatic dysfunction.
  • It is unknown if the dose, duration, and concomitant use of medication affect risk.
  • Although monitoring serum aminotransferases is not shown to protect against serious liver injury, it may be possible to detect the condition early and withdraw from drugs.
  • You should obtain baseline levels of transaminase and then check them periodically.
  • Stop using if transaminase levels rise to >=2x the normal limit or if you have signs/symptoms that indicate hepatic dysfunction.
  • Patients with evidence of liver damage or those who have stopped using the medication for any reason should not be given therapy.

• Suicidal thoughts:

  • A pooled analysis of antiepileptic trials (regardless the indication) revealed an increase in suicidal thoughts/behavior.
  • The incidence rate was 0.43% for patients treated, compared to 0.2% for patients who received placebo.
  • Risk can be observed as soon as one week after initiation, and continues throughout the trial (most trials last less than 24 weeks).
  • All patients should be monitored for any changes in behavior that could indicate depression or suicidal thoughts.
  • If symptoms persist, immediately notify your healthcare provider.

• Renal impairment

  • Patients with impaired renal function should be cautious.
  • Half-life could be extended

Felbamate: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Serum levels of concomitant anticonvulsant therapy.
• liver function tests (baseline and periodically thereafter).
• CBC (baseline, frequently during therapy, and for a significant period after discontinuation).
• suicidality (eg, suicidal thoughts, depression, behavioral changes).

How to administer Felbamate?

• Administer with or without food.
• Shake suspension of felbamate prior to use.

Mechanism of action of Felbamate:

• Although the mechanism of action is not known, it shares many properties with anticonvulsants on the market.
• It has weak inhibitory properties on GABA receptor binding and benzodiazepine receiver binding.

Absorption:

• Rapid and almost complete;
• food has no effect upon the tablet's absorption

Protein binding:

• 22% to 25%, primarily to albumin

Half-life elimination:

• 20 to 23 hours (average);
• prolonged by 9 to 15 hours in patients with renal impairment

Bioavailability:

• ≥80%

Time to peak, serum:

• 2 to 6 hours.

Excretion:

• Urine (40% to 50% as unchanged drug, 40% as inactive metabolites)

Clearance:

• clearance is decreased in renal impairment (40% to 50%).
• Clearance is faster in children than adults (20% to 65%) (Perucca 2006), particularly younger children.

International Brand Names of Felbamate:

• Felbatol
• Alopileptic
• Felbamyl
• Taloxa

Felbamate Brand Names in Pakistan:

No Brands Available in Pakistan.