Pronunciation:

FEL-ba-mate

Brand Names:

• Felbatol

Dosage Forms:

• Tablet
• Suspension

Warnings:

The use of felbamate is associated with a marked increase in the incidence of aplastic anemia. Accordingly, felbamate should only be used in patients whose epilepsy is so severe that the risk of aplastic anemia is deemed acceptable in light of the benefits conferred by its use. Ordinarily, a patient should not be placed on and/or continued on felbamate without consideration of appropriate expert hematologic consultation.

Among felbamate treated patients, aplastic anemia (pancytopenia in the presence of a bone marrow largely depleted of hematopoietic precursors) occurs at an incidence that may be more than a 100 fold greater than that seen in the untreated population (ie, 2 to 5 per million persons per year). The risk of death in patients with aplastic anemia generally varies as a function of its severity and etiology; current estimates of the overall case fatality rate are in the range of 20% to 30%, but rates as high as 70% have been reported in the past.

There are too few felbamate associated cases, and too little known about them to provide a reliable estimate of the syndrome's incidence or its case fatality rate or to identify the factors, if any, that might conceivably be used to predict who is at greater or lesser risk.

In managing patients on felbamate, it should be borne in mind that the clinical manifestation of aplastic anemia may not be seen until after a patient has been on felbamate for several months (eg, onset of aplastic anemia among felbamate exposed patients for whom data are available has ranged from 5 weeks to 30 weeks). However, the injury to bone marrow stem cells that is held to be ultimately responsible for the anemia may occur weeks to months earlier. Accordingly, patients who are discontinued from felbamate remain at risk for developing anemia for a variable, and unknown, period afterwards.

It is not known whether or not the risk of developing aplastic anemia changes with duration of exposure. Consequently, it is not safe to assume that a patient who has been on felbamate without signs of hematologic abnormality for long periods of time is without risk.

It is not known whether or not the dose of felbamate affects the incidence of aplastic anemia.

It is not known whether or not concomitant use of antiepileptic drugs and/or other drugs affects the incidence of aplastic anemia.

Aplastic anemia typically develops without premonitory clinical or laboratory signs, the full blown syndrome presenting with signs of infection, bleeding, or anemia. Accordingly, routine blood testing cannot be reliably used to reduce the incidence of aplastic anemia, but, it will, in some cases, allow the detection of the hematologic changes before the syndrome declares itself clinically. Felbamate should be discontinued if any evidence of bone marrow depression occurs.

Evaluation of postmarketing experience suggests that acute liver failure is associated with the use of felbamate. The reported rate in the US has been about 6 cases of liver failure leading to death or transplant per 75,000 patient years of use. This rate is an underestimate because of under reporting, and the true rate could be considerably greater than this. For example, if the reporting rate is 10%, the true rate would be one case per 1,250 patient years of use.

Of the cases reported, about 67% resulted in death or liver transplantation, usually within 5 weeks of the onset of signs and symptoms of liver failure. The earliest onset of severe hepatic dysfunction followed subsequently by liver failure was 3 weeks after initiation of felbamate. Although some reports described dark urine and nonspecific prodromal symptoms (eg, anorexia, malaise, and gastrointestinal symptoms), in other reports it was not clear if any prodromal symptoms preceded the onset of jaundice.

It is not known whether or not the risk of developing hepatic failure changes with duration of exposure.

It is not known whether or not the dosage of felbamate affects the incidence of hepatic failure.

It is not known whether concomitant use of other antiepileptic drugs and/or other drugs affect the incidence of hepatic failure.

Felbamate should not be prescribed for anyone with a history of hepatic dysfunction.

Treatment with felbamate should be initiated only in individuals without active liver disease and with normal baseline serum transaminases. It has not been proved that periodic serum transaminase testing will prevent serious injury but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. There is no information available that documents how rapidly patients can progress from normal liver function to liver failure, but other drugs known to be hepatotoxins can cause liver failure rapidly (eg, from normal enzymes to liver failure in 2 weeks to 4 weeks). Accordingly, monitoring of serum transaminase levels (AST and ALT) is recommended at baseline and periodically thereafter. While the more frequent the monitoring the greater the chances of early detection, the precise schedule for monitoring is a matter of clinical judgement.

Felbamate should be discontinued if either serum AST or serum ALT levels become increased greater than or equal to 2 times the upper limit of normal, or if clinical signs and symptoms suggest liver failure. Patients who develop evidence of hepatocellular injury while on felbamate and are withdrawn from the drug for any reason should be presumed to be at increased risk for liver injury if felbamate is reintroduced. Accordingly, such patients should not be considered for re-treatment .

Felbamate use is associated with a marked increase in the incidence of aplastic anemia, sometimes fatal. Discontinue if any evidence of bone marrow depression occurs. Liver failure resulting in death or transplant has been reported with therapy. Should not be prescribed for anyone with a history of hepatic dysfunction and should be discontinued in anyone showing signs of liver injury while on therapy. Monitor liver enzymes during therapy .

Classifications:

Therapeutic—

Anticonvulsant

Chemical—

Carbamate

Uses of This Medicine:

Felbamate is used to control some types of seizures in the treatment of epilepsy. Felbamate acts on the central nervous system (CNS) to make it more difficult for seizures to start or to continue. This medicine cannot cure epilepsy and will only work to control seizures for as long as you continue to use it.

Felbamate is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

This medicine has some very serious unwanted effects. Children may not be able to tell their parent or guardian or their doctor if they have symptoms of these effects, such as chills or stomach pain. Felbamate should be used in children only if other medicines have not controlled their seizures.

Older adults—

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of felbamate in the elderly with use in other age groups. However, older people are more likely to have other illnesses and to use other medicines that may affect the way felbamate works. Your doctor may start with a lower felbamate dose or may increase the dose more slowly.

Pregnancy—

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ethinyl Estradiol
• Gestodene

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or other blood problems (or history of) or
• Liver problems (or history of)—Felbamate may make the condition worse

Proper Use of This Medicine:

Take this medicine only as directed by your doctor, to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

For patients taking the oral liquid form of this medicine:

• Shake the bottle well before measuring the dose.
• Use a specially marked measuring spoon, a plastic syringe, or a small marked measuring cup to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid.

To lessen stomach upset, felbamate may be taken with food, unless your doctor has told you to take it on an empty stomach.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (suspension or tablets):
  • For epilepsy:
    • Adults and teenagers 14 years of age and older—At first, usually 1200 milligrams (mg) a day, divided into three or four smaller doses. Your doctor may increase the dose gradually over several weeks if needed. However, the dose is usually not more than 3600 mg a day.
    • Children 2 to 14 years of age—At first, usually 15 mg per kilogram (kg) [6.8 mg per pound] of body weight per day, divided into smaller doses that are given three or four times during the day. Your doctor may increase the dose gradually over a few weeks if needed. However, the dose is usually not more than 45 mg per kg [20.5 mg per pound] or 3600 mg per day, whichever is less.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using This Medicine:

It is important that your doctor check your progress at regular visits. This is necessary to allow dose adjustments and to test for serious unwanted effects.

Do not stop taking felbamate without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping completely. Stopping the medicine suddenly may cause your seizures to return or to occur more often.

Felbamate may cause blurred vision, double vision, or other changes in vision. It may also cause some people to become dizzy or drowsy. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert or able to see well. If these reactions are especially bothersome, check with your doctor.

Side Effects of This Medicine:

Felbamate may cause some serious side effects, including blood problems and liver problems. You and your doctor should discuss the good this medicine will do as well as the risks of receiving it.

Along with its needed effects, a medicine may cause some unwanted effects. Some side effects will have signs or symptoms that you can see or feel. Your doctor may watch for others by doing certain tests. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Fever

purple or red spots on skin

Rare

Black or tarry stools

blood in urine or stools

chills

continuing headache

continuing stomach pain

continuing vomiting

dark-colored urine

general feeling of tiredness or weakness

light-colored stools

nosebleeds or other unusual bruising or bleeding

shortness of breath, trouble in breathing, wheezing, or tightness in chest

sore throat

sores, ulcers, or white spots on lips or in mouth

swelling of face

swollen or painful glands

yellow eyes or skin

Check with your doctor as soon as possible if any of the following side effects occur:

More common

Walking in unusual manner

Less common

Agitation, aggression, or other mood or mental changes

clumsiness or unsteadiness

skin rash

trembling or shaking

Rare

Chest pain

hives or itching

muscle cramps

nasal congestion

pain

sensitivity of skin to sunlight

swollen lymph nodes

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Change in your sense of taste

constipation

difficulty in sleeping

dizziness

headache

indigestion

loss of appetite

nausea

stomach pain

vomiting

Less common

Blurred or double vision

coughing

diarrhea

drowsiness

ear congestion or pain

runny nose

sneezing

weight loss

This medicine may also cause the following side effects that your doctor will watch for:

Rare

Blood problems

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.