Felbamate

Felbatol is the brand name used in the United States for felbamate. Felbamate is not available in Canada, the UK, or Australia. It is available in some European countries using the name Taloxa (manufactured by Schering Plough).

When Felbatol was introduced in 1993, it carried high expectations. Many hoped it would be able to control seizure disorders that had not been controlled before. Unfortunately, after only 1 year the FDA recommended withdrawal of patients from Felbatol because of reports of very serious side effects (aplastic anemia or liver failure). The evidence discouraged both patients and doctors from using Felbatol, and many doctors do not even consider prescribing the drug.

Felbatol
Tablet
Felbitol 400

400-mg (yellow, scored, capsule-shaped)

Felbitol 600

600-mg (peach-colored, scored, capsule-shaped)

Liquid Solution

600 mg/5 mL peach-colored liquid

Indications

Felbatol is effective as:

  • monotherapy and adjunctive therapy for partial-onset seizures and tonic-clonic seizures in adults 14 years of age and older
  • adjunctive therapy for partial and generalized seizures, including the atonic seizures associated with Lennox-Gastaut syndrome, in children aged 2 to 14 years

Felbatol is recommended only for those patients whose epilepsy is so severe that a substantial risk of aplastic anemia or liver failure is considered acceptable in light of the potential benefits of its use. If these criteria are met, and the patient has been fully advised of the risk, Felbatol can be considered for use either alone or in combination with other seizure medicines.

Before deciding to prescribe Felbatol, read the information on Serious Side Effects on this site. Read the black box warning in the Package Insert to your patient and obtain any necessary signatures. The package insert includes a model patient consent form, but no special form is required.

Forms

Felbatol is marketed in the United States by Medpointe Pharmaceuticals. These descriptions apply to the U.S. versions:

Dosing

See package insert.

How to take and store Felbamate?

Felbatol can be taken either with food or without food.

Advise patients who are using the suspension form of Felbatol to shake the bottle well before measuring it and to use the same accurate measuring spoon each time so the dose will be correct. The bottle should be stored at room temperature and kept out of the reach of children.

There have been no reports of serious harm resulting from an overdose of Felbatol.

Missed Doses

In general, tell patients that if they forget a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should delay that dose for a few hours, instead of taking two doses very close together.

Patients who often forget doses may benefit from using a special pillbox or watch with an alarm.

Mechanisms of actions of Felbamate

Felbatol potentiates gamma aminobutyric acd (GABA) function, and blocks voltage-dependent sodium channels as well as the ionic channel at the N-methyl-D-aspartate excitatory amino acid receptor in vitro. Therefore, Felbatol may modulate both inhibitory and excitatory synaptic functions.

Clinical Pharmacology of Felbamate

Absorption

Felbatol is well absorbed after being given by mouth. The peak concentration of medication in the blood is reached in 1 to 6 hours. This applies equally to the tablet and liquid suspension forms of Felbatol. Food does not affect the absorption of the tablets. The effect of food on the absorption of the liquid form has not been studied.

Distribution and metabolism

Felbatol is approximately 25% bound to plasma protein and is approximately 50% metabolized by the hepatic cytochrome P450 system.

Over 90% is excreted in the urine (40% to 50% as the unchanged drug).

Steady state

The half-life of Felbatol is 20 to 23 hours and remains constant after multiple doses. Steady state is reached after about 4 to 7 days of taking a stable dose of Felbatol. Levels in the blood then can be expected to be constant. The dose that a patient takes should not be increased until steady state has been reached (or some time later), so that the effects of the previous dose can be assessed.

Efficacy of Felbamate

Because of concerns that it increases patients' risk of a few rare but serious disorders, Felbatol (felbamate) is used very rarely. For patients with severe epilepsy that is not well controlled by other seizure medicines, however, it may be worth considering, either alone or as an add-on. The patient must be fully informed of the risk before the treatment begins.

Felbatol is effective in treating partial seizures with and without generalization. A study that compared Felbatol alone with Depakote (valproate) alone in treating patients with previously uncontrolled partial seizures found a significant difference in favor of Felbatol (Faught et al. 1993). The patients who took Felbatol reported only mild or moderate adverse side effects, which were less common after other medications had been stopped.

Another study that did compare Felbatol to a placebo (with patients who were in the hospital for 10 days while being evaluated for epilepsy surgery) also showed that Felbatol is effective in controlling partial seizures when used alone (Devinsky et al. 1995).

Felbatol is also used as adjunctive (add-on) therapy for partial and generalized seizures associated with Lennox-Gastaut syndrome, a condition that is usually difficult to treat effectively. The 73 patients in one study continued to take their previous medications, to which was added either Felbatol or a placebo (Felbamate Study Group, 1993). After the dosages had been stabilized, the patients given felbamate had 26% fewer seizures than during the baseline period, compared with a 5% increase among the patients given the placebo. Unfortunately, the serious side effects caused by Felbatol in some people limits its use to patients who have not responded to other antiepileptic drugs.

Common side effects of Felbamate

Dose-related side effects

Side effects most often reported by patients taking Felbatol have included:

  • decreased appetite and weight loss
  • nausea
  • insomnia
  • headache

Some other side effects mentioned even less often were:

  • poor coordination or tremor
  • vision problems
  • dizziness
  • vomiting
  • mood changes or anxiety
  • somnolence (when part of polytherapy)

If these problems do not diminish within several days, a reduction in the dose of Felbatol often will solve the problem. Problems with somnolence also may be helped by splitting the dose or giving the largest dose at bedtime.

Idiosyncratic reactions

Rash is seen in a small percentage of patients. This reaction usually occurs early in the course of therapy. Most patients will need to stop taking Felbatol and replace it with a different antiepileptic medication.

Serious Side effects of Felbamate

The chance that a particular patient will develop liver failure or aplastic anemia while taking Felbatol appears to be approximately 1 out of 4,500.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10.

Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;

  • Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
  • Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.

Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:

  •  Talking or thinking about wanting to hurt yourself or end your life
  •  Withdrawing from friends and family
  •  Becoming depressed or having your depression get worse
  •  Becoming preoccupied with death and dying
  •  Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

Impact of Felbamate on bone health

See package insert.

Other Uses of Felbamate

There are no off-label uses of Felbatol.

Felbamate Contraindications

Physicians and patients must read the black box warning in the package insert. Because of the risk of fatal aplastic anemia and liver failure, use should be reserved for patients in whom the risk-benefit ratio is favorable.

Patients who are allergic to felbamate or to other carbamates should not take Felbatol. Neither should those who have had any liver disease, blood disorder, or autoimmune disease.

Felbamate Interactions with other medications

Effects of Felbatol on other drugs

Felbatol will lower the blood levels of:

  • carbamazepine (but the level of the active metabolite carbamazepine epoxide is increased)

Felbatol will increase the blood levels of some other AEDs:

  • phenytoin
  • valproate
  • phenobarbital
  • carbamazepine epoxide (the active metabolite of carbamazepine

Effects of other drugs on Felbatol

If Felbatol is added as adjunctive therapy with another AED, or the other AED is withdrawn while Felbatol is in use, the dosages may need to be adjusted to accommodate interactions.

These other AEDs may decrease the blood level of Felbatol:

  • phenytoin
  • carbamazepine
  • phenobarbital

Valproate may increase the blood level of Felbatol.

AED Interaction Sheets:

Seizure drugs are often affected by drug-drug interactions. Print these informative sheets for practical help.

Interaction sheet for felbamate (Felbatol)

Felbamate effects on Children

Felbatol (felbamate) is approved by the FDA to treat patients 14 years and older for partial epilepsy, both as adjunctive therapy and monotherapy. It also is approved for adjunctive therapy for generalized epilepsy associated with Lennox-Gastaut syndrome in patients 2 years and older.

Felbatol used as adjunctive therapy for Lennox-Gastaut syndrome should be added at 15 mg/kg per day in three or four divided doses. The dosage of Felbatol is increased by 15 mg/kg per day at weekly intervals until seizures are brought under control or unacceptable side effects occur. A typical maintenance dose for long-term use is 15-45 mg/kg per day.

If the suspension is used, stress the importance of thoroughly shaking the bottle immediately before measuring.

Felbamate and Pregnancy

The U.S. Food and Drug Administration (FDA) lists Felbatol in Pregnancy Category C. This indicates that caution is advised. There have been no studies in women. Studies in animals have not shown malformations but have shown harm during lactation.

The risk of birth defects is higher for women who take more than one AED and for women with a family history of birth defects.

Advise women who are capable of becoming pregnant to take at least 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent neural tube defects. Women at high risk, such as those with a history of a neural tube defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant. The effectiveness of prophylactic folic acid use in preventing defects related to Felbatol has not been proven, however, so diagnostic ultrasonography at the 18th to 20th week is recommended, especially if pregnancy termination is an option.

About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how their AED is handled by the body. It is unclear if Felbatol is affected in this way, so it is advisable to check the blood levels of Felbatol regularly during pregnancy so that the dosage can be adjusted as needed.

The effect of Felbatol in breast milk on healthy, full-term newborns is unknown.

Felbamate effects on Seniors

In light of the substantial risks of Felbatol and the availability of many safer AEDs for partial seizures, Felbatol should be a drug of last resort for seniors. Lower initial and maintenance doses should be used.

Another difficulty with the use of Felbatol in seniors is interactions with other medications. In addition, dose-related side effects of Felbatol may be accentuated in seniors.

Felbamate Dosing and titration

In young adults, Felbatol is usually started at 600-1,200 mg per day in 3 to 4 divided doses. Every 7 to 14 days, the amount can be increased by 600 to 1,200 mg per day as required (if side effects are not troublesome), to a maximum dose of 3,600 mg day in 3-4 divided doses.

In children over 6, the starting dose is 15 mg/kg per day in 3 to 4 divided doses. The usual maintenance dose is 15-45 mg/kg per day, usually in 3 to 4 divided doses.

Refer to the Package Insert for guidance on Felbatol dosages and dosage reductions of concomitant AEDs during first 3 weeks of use.

Therapeutic levels of Felbatol have not been established.

Routine monitoring of liver and bone marrow function is recommended, but does not predict the occurrence of potentially fatal liver and bone marrow failure.

Special Concerns for Felbamate

See package insert.

Felbamate Package insert

In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a “package insert” because it is usually included with each package of the medicine.

You can also read these documents (also called "prescribing information") online. The U.S. package insert for Felbatol is found at:

Some of the information may differ in other countries.

To learn how to read and understand a package insert, see How to read a package insert.

Felbamate References for Professionals

Faught E, Sachdeo RC, Remler MP, et al.: Felbamate monotherapy for partial-onset seizures: an active-control trial. Neurology 1993 Apr;43(4):688-92. PMID: 8469323.

The Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). N Engl J Med 1993 Jan 7;328(1):29-33. PMID: 8347179.

Kaufman DW, Kelly JP, Anderson T, Harmon DC, Shapiro S: Evaluation of case reports of aplastic anemia among patients treated with felbamate. Epilepsia 1997 Dec;38(12):1261-4.

Pellock JM: Felbamate. Epilepsia 1999;40 Suppl 5:S57-62.

Thompson CD, Barthen MT, Hopper DW, et al: Quantification in patient urine samples of felbamate and three metabolites: acid carbamate and two mercapturic acids. Epilepsia 1999 Jun;40(6):769-76.

Welty TE, Privitera M, Shukla R: Increased seizure frequency associated with felbamate withdrawal in adults. Arch Neurol 1998 May;55(5):641-5.

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