Felbamate (marketed under the brand name Felbatol by MedPointe) is an

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

used in the treatment of

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

. It is used to treat

partial seizure Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...

s (with and without generalization) in adults and partial and generalized seizures associated with

Lennox–Gastaut syndrome Lennox–Gastaut syndrome (LGS) is a complex, rare, and severe childhood-onset epilepsy. It is characterized by multiple and concurrent seizure types, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG). Typically, it presents ...

in children. However, an increased risk of potentially fatal

aplastic anemia Aplastic anemia is a cancer in which the body fails to make blood cells in sufficient numbers. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red bloo ...

and/or liver failure limit the drug's usage to severe refractory epilepsy.

Mechanism of action

Felbamate has been proposed to have a unique dual mechanism of action as a positive modulator of GABA_A receptors and as a blocker of

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...

s, particularly isoforms containing the

NR2B Glutamate MDAreceptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the ''GRIN2B'' gene. NMDA receptors ''N''-methyl-D-aspartate (NMDA) receptors are ...

subunit. Although it is clear that felbamate does cause pharmacological inhibition of NMDA receptors, the relevance of NMDA receptor blockade as a strategy for the treatment of human epilepsy has been questioned. Therefore, the importance of the effects of felbamate on NMDA receptors to its therapeutic action in epilepsy is uncertain.

Approval history

United States

* August 1993. Felbamate was approved for partial seizures with and without secondary generalization in adults and for Lennox–Gastaut Syndrome, a serious form of childhood epilepsy. Over the following year 150,000 people were started on felbamate therapy and a third of these became established. * August 1, 1994. It was urgently withdrawn after 10 cases of aplastic anemia. A "Dear Doctor" letter was sent to 240,000 physicians. * September 27, 1994. Felbamate had a limited redemption in another "Dear Doctor" letter sent to 260,000 physicians. It was recommended that the drug remain available only for patients with severe epilepsy for whom the benefits outweigh the risks, and that changes be made to the product's labelling to reflect the newly recognized risk. This redemption came with an additional warning since there had been 10 cases acute liver failure (4 of which were fatal). At this point, 10,000 to 12,000 people remained on the drug.

United Kingdom

* The drug is only available on a limited named-patient basis.

Indications and usage

* Adults: Monotherapy or adjunctive therapy in the treatment of partial seizures, with and without generalization. * Children: Adjunctive therapy in the treatment of partial and generalized seizures associated with Lennox-Gastaut syndrome.

Dosing

Felbamate is available in tablets (400 mg and 600 mg) and as a peach-coloured oral suspension (600 mg/5 mL). * Adults (≥ 14 years): begin with 1,200 mg daily given every 6 to 8 hours * Children (2–14 years): 15 to 45 mg per kg per day given every 6 to 8 hours

Side effects

Adverse reactions include decreased appetite, vomiting,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, nausea, dizziness, somnolence, and headache. Many patients report increased alertness with the drug. Two rare but very serious effects include

and serious liver damage. The risk of aplastic anemia is between 1:3,600 and 1:5,000, of which 30% of cases are fatal. The risk of liver damage is between 1:24,000 to 1:34,000, of which 40% of cases are fatal.

Drug interactions

Felbamate is an

inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some p ...

- an enzyme involved in the

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run ...

of several commonly used medications. Retrieved on December 25, 2008. Felbamate interacts with several other AEDs, including

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The in ...

valproate Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those ...

, and

carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...

; dosage adjustments may be necessary to avoid adverse effects. Concomitant administration of felbamate and carbamazepine decreases blood levels of both drugs, while increasing the level of ''carbamazepine-10,11 epoxide'', the active

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

of carbamazepine.

History

Felbamate was discovered by

Frank Berger Frank Milan Berger (June 25, 1913 - March 18, 2008) was a Czechoslovakian pharmacologist who discovered meprobamate, carisoprodol, and felbamate, while working at Wallace Laboratories. He also discovered the 'tranquilising' effects of mephenesin ...

at Wallace Laboratories.

References

External links

Felbatol: Prescribing Information

contains extensive information including the patient warning and a sample consent form.
Hard Choices with Felbamate

* ttps://web.archive.org/web/20100516151204/http://medpointepharma.com/ MedPonte Pharmaceuticals {{Ionotropic glutamate receptor modulators Anticonvulsants Carbamates GABAA receptor positive allosteric modulators NMDA receptor antagonists Czech inventions