Felbamate is an anticonvulsant

Anticonvulsant

The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...

 drug used in the treatment of epilepsy

Epilepsy

Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

. It is used to treat partial seizure

Seizure

An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s (with and without generalization) in adults and partial and generalized seizures associated with Lennox-Gastaut syndrome

Lennox-Gastaut syndrome

Lennox–Gastaut syndrome , also known as Lennox syndrome, is a difficult-to-treat form of childhood-onset epilepsy that most often appears between the second and sixth year of life, and is characterized by frequent seizures and different seizure types; it is often accompanied by developmental delay...

 in children. However, an increased risk of potentially fatal aplastic anemia

Aplastic anemia

Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. The condition, per its name, involves both aplasia and anemia...

 and/or liver failure

Liver failure

Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...

 limit the drugs usage to severe refractory epilepsy.

Mechanism of action

As with many anticonvulsants, the precise mechanism is unknown.

It has an effect on GABA

Gabâ

Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...

 receptor binding sites.

It may also work as a NMDA receptor antagonist

NMDA receptor antagonist

NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-methyl d-aspartate receptor . They are used as anesthesia for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia...

.

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.

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

Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

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

Aplastic anemia

Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. The condition, per its name, involves both aplasia and anemia...

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

Drug interactions

Felbamate is an inhibitor

Enzyme inhibitor

An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

 of CYP2C19

CYP2C19

Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...

, an isoenzyme of the cytochrome P450 system involved in the metabolism

Drug metabolism

Drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...

 of several commonly used medications. Felbamate interacts with several other AEDs, including phenytoin

Phenytoin

Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...

, valproate, and carbamazepine

Carbamazepine

Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...

; 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

Metabolite

Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

of carbamazepine.

External links

• Felbatol: Prescribing Information
• RxList: Felbamate contains extensive information including the patient warning and a sample consent form.
• Hard Choices with Felbamate
• Newer Antiepileptic Drugs: Gabapentin, Lamotrigine, Felbamate, Topiramate and Fosphenytoin
• MedPonte Pharmaceuticals