An oral medication called felbamate is used to treat children with Lennox-Gastaut Syndrome-related generalised seizures as well as partial seizures in adults.

Felbamate Uses:

• Partial seizures (monotherapy or adjunctive):

  • Felabamate is used as a monotherapy or supplementary therapy to treat partial seizures in adults and adolescents 14 years of age and older, both with and without generalisation.

• Lennox-Gastaut syndrome:

  • It is used in conjunction with other therapies to treat children with Lennox-Gastaut syndrome's partial and generalised seizures.
  • Restrictions on use: Lennox-Gastaut Syndrome first-line therapy is not recommended.

Felbamate Dose in Adults

Felbamate Dose in the monotherapy of Partial seizures:

• 1,200 mg orally, three to four times a day at first.
• Titrate patients who had not previously received treatment while under under medical supervision, increasing the dosage by 600 mg every two weeks to 2400 mg/day depending on the patients' clinical responses, and then to 3,600 mg/day.

• Conversion to monotherapy:

  • Start with 1,200 mg per day in three to four divided doses.
  • When felbamate medication is started, the dosage of any concurrent anticonvulsant(s) should be decreased by 33%.
  • When you reach week 2, boost the felbamate dosage to 2,400 mg per day while lowering the dosage of the other anticonvulsant(s) by an additional 33% of the recommended dosage.
  • Increase the felbamate dosage to 3,600 mg/day at week 3 and keep lowering the dose of the other anticonvulsant(s) as prescribed by a doctor.

Felbamate Dose in the adjunctive therapy of partial seizures:

• Oral: 1,200 mg/day in three to four divided doses at first; 1,200 mg/day increases once per week up to 3,600 mg/day in three to four divided doses.

Note: When starting felbamate therapy, reduce the dosage of concurrent carbamazepine (including carbamazepine metabolites), phenytoin, phenobarbital, or valproic acid by 20%.

Felbamate Dose in Children

Felbamate Dose as Anticonvulsant (adjunctive therapy):

• Adolescents ≥14 years:

  • Oral: Initial dose: 1,200 mg/day, divided into 3 or 4 doses.
  • Weekly dosage increases of 1,200 mg/day are recommended.
  • 3,600 mg/day is the highest daily dosage.
  • Reminder: When starting felbamate therapy, reduce the dose of any concurrent medications by 20%, including carbamazepine, phenytoin, phenobarbital, and valproic acid. As the felbamate dosage is raised, further dosage reductions might be required.

Felbamate Dose as Anticonvulsant (Monotherapy):

• Adolescents ≥ 14 years: Oral:

  • Initial: 1,200 mg/day, divided into three or four dosages each day.
  • Patients who have never been treated before should be titrated, with the dose being increased in 600 mg/day increments every two weeks to 2,400 mg/day based on clinical response and then to 3,600 mg/day if clinically necessary.

• Conversion to monotherapy:

  • At the beginning of felbamate therapy, the dosage of the concomitant anticonvulsant(s) should be decreased by 33%. At the beginning of week 2, the felbamate daily dose should be increased to 2000 mg/day in 3-4 divided doses while the other anticonvulsant(s) should be reduced by up to an additional 33% of their original dose.
  • Increase the felbamate dosage to a daily maximum of 3,600 mg at week 3, while continuing to lower the dosage of the other anticonvulsant(s) as clinically necessary.

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

• Children and Adolescents 2 to 14 years:

  • Oral: The initial dose is 15 mg/kg/day, divided into 3 or 4 doses.
  • Weekly intervals will be used to gradually increase the felbamate dose by 15 mg/kg/day.
  • The maximum daily dose is either 3,600 mg/day or 45 mg/kg/day, whichever is lower.

Note: Reduce the dose of concurrent carbamazepine, phenytoin, phenobarbital, or valproic acid by 20% when felbamate is started. As the felbamate dosage is raised, further dosage reductions might be required

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%.
• In individuals with renal failure, adjunctive therapy with drugs such AEDs, which impact felbamate plasma concentrations, may call for further felbamate dose reductions.

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
• Sensitivity to any ingredient in the mix, including carbamates
• 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.
  • The current fatality rate ranges from 20% to 30%. Higher percentages (up to 70%) have, however, been noted in previous years.
  • Fetal anaemia can develop at any point while receiving felbamate medication or even after it has ceased.
  • It is unknown if the dose, duration, and concomitant use of medication affect risk.
  • In order to identify hematologic indications and symptoms before they become clinically evident, routine blood monitoring can be helpful.
  • 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]

  • Felbamate has been connected to a small number of cases of hepatic impairment (estimated at >6 cases per 75,000 people yearly).
  • In 67% of the cases detailed in the literature, the patient either died or required a liver transplant.
  • 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.
  • Patients who received treatment experienced an incidence rate of 0.43% compared to patients who got a placebo at 0.2%.
  • Risk can be seen as soon as one week after the trial's start and persists throughout (most trials last less than 24 weeks).
  • Every patient needs to be watched carefully for any behavioural changes that can point to sadness or suicidal ideation.
  • 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?

• Both with and without food, administer.
• Before using, shake the felbamate suspension.

Mechanism of action of Felbamate:

• Although the mechanism of action is not known, it shares many properties with anticonvulsants on the market.
• It has negligible inhibitory effects on benzodiazepine and GABA receptor 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%).
• Children, especially younger children, clear more quickly than adults (20% to 65%) (Perucca 2006).

International Brand Names of Felbamate:

• Felbatol
• Alopileptic
• Felbamyl
• Taloxa

Felbamate Brand Names in Pakistan:

No Brands Available in Pakistan.