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Felbamate

 

Definition

Felbamate is an anticonvulsant indicated for the control of seizures in the treatment of epilepsy, a neurological dysfunction in which excessive surges of electrical energy are emitted in the brain.

Purpose

Felbamate is thought to decrease abnormal activity and excitement within the central nervous system (CNS) that may trigger seizures. While felbamate controls some types of seizures associated with epilepsy, there is no known cure for the disorder. Felbamate has shown effectiveness in controlling partial seizures in adults when prescribed alone. When prescribed with other antiepileptic medicines, felbamate has shown effectiveness in managing the intractable (difficult to control) seizures of Lennox-Gastaut syndrome in children.

Description

In the United States, felbamate is sold under the brand name Felbatol and FBM. Felbamate acts to depress CNS function; however the precise mechanisms by which it exerts its therapeutic effects in the prevention of seizures is unknown.

Recommended dosage

Felbamate is taken by mouth and is available in tablet or oral suspension form. Adult patients usually take felbamate three to four times daily. The typical total daily dose for an adult or teenager over 14-years-old ranges from 1200 mg to 3600 mg. Treatment including felbamate is appropriate for some children with intractable seizures. The typical total daily dosage formula for a child is between 15 mg and 45 mg per kilogram of body weight.

Beginning a course of treatment which includes felbamate requires a gradual dose-increasing regimen. Patients typically take a reduced dose at the beginning of treatment. The prescribing physician will determine the proper beginning dosage and may raise a patient's daily dosage gradually over the course of several weeks. It may take several weeks to realize the full benefits of felbamate.

It is important to not take a double dose of felbamate. If a daily dose is missed, take it as soon as possible. However, if it is almost time for the next dose, then skip the missed dose. When ending treatment for epilepsy that includes felbamate, physicians typically direct patients to gradually taper their daily dosages. Stopping the medicine suddenly may cause seizures to return or occur more frequently.

Precautions

Prior to initiating therapy with felbamate, blood tests to check for anemia, infection, and liver function will likely be performed. Periodic blood tests are necessary to monitor liver and bone marrow function while receiving felbamate therapy, and for a period after the drug is discontinued.

Felbamate may not be suitable for persons with a history of stroke, anemia, liver or kidney disease, mental illness, diabetes, high blood presure, angina (chest pain), irregular heartbeats, or other heart problems.

Before beginning treatment with felbamate, patients should notify their physician if they consume a large amount of alcohol, have a history of drug use, are pregnant, nursing, or plan on becoming pregnant. Research in animals indicates that felbamate may inhibit fetal growth and development. Patients who become pregnant while taking felbamate should contact their physician.

Consult a physician before taking felbamate with certain non-perscription medications. Patients should avoid alcohol and CNS depressants (medicines that can make one drowsy or less alert, such as antihistimines, sleep medications, and some pain medications) while taking felbamate.

Side effects

Patients should discuss with their physicians the risks and benefits of treatment including felbamate before taking the medication. Dizziness and nausea are the most frequently reported side effects. Most mild side effects do not require medical treatment, and may diminish with continued use of the medication. Additional possible mild side effects include anorexia (loss of appetite), vomiting, insomnia, headache, and sleepiness. If any symptoms persist or become too uncomfortable, the prescribing physician should be consulted.

Felbamate has been implicated as the cause of serious side effects, including plastic anemia (bone marrow failure) and liver failure. It is estimated that one in every 3,600 to 5,000 patients taking felbamate will eventually develop aplastic anemia, and the fatality rate of complicating aplastic anemia is nearly 30%. For this reason, felbamate is prescribed seldomly, and only after other medications have failed to control seizures. Persons taking felbamate who experience any of the following symptoms should immediately contact a physician:

  • rash or purple spots on skin
  • nosebleed
  • yellow tint to eyes or skin
  • bruising easily
  • signs of infection
  • weakness and fatigue

Interactions

Felbamate should be used with other other seizure prevention medications (anticonvulsants or anti-epileptic drugs [AEDs]), only if prescribed by a physician. Felbamate increases blood levels of phenytoin (Dilantin) and valproic acid (Depekene), while reducing blood levels of carbamazepine (Tegretol).

Felbamate, like many other anticonvulsants, may decrease the effectiveness of oral contraceptives (birth control pills) or contraceptives containing estrogen.

Resources

BOOKS

Devinsky, Orrin, M.D. Epilepsy: Patient and Family Guide, 2nd. ed. Philadelphia: F. A. Davis Co., 2001.

Weaver, Donald F. Epilepsy and Seizures: Everything You Need to Know. Toronto: Firefly Books, 2001.

OTHER

Dodson, W. Edwin. M.D. Hard Choices with Felbamate. Washington University School of Medicine. (April 23, 2004). http://www.neuro.wustl.edu/epilepsy/pediatric/articleFelbamate.html

"Felbamate (Systemic)." Medline Plus. National Library of Medicine. (April 23, 2004). http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202711.html

ORGANIZATIONS

American Epilepsy Society. 342 North Main Street, West Hartford, CT 06117-2507, USA. http://www.aesnet.org.

Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. http://www.epilepsyfoundation.org.


Adrienne Wilmoth Lerner


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Veterinary Dictionary: felbamate
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A dicarbamate anticonvulsant.

Wikipedia: Felbamate
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Felbamate
Systematic (IUPAC) name
(3-carbamoyloxy-2-phenylpropyl) carbamate
Identifiers
CAS number 25451-15-4
ATC code N03AX10
PubChem 3331
DrugBank APRD00505
Chemical data
Formula C11H14N2O4 
Mol. mass 238.24
Pharmacokinetic data
Bioavailability > 90%
Metabolism Hepatic
Half life 20-23 hours
Excretion  ?
Therapeutic considerations
Pregnancy cat.

C (USA)

Legal status

Unscheduled

Routes Oral

Felbamate (marketed under the brand name Felbatol by MedPointe) is an anticonvulsant drug[1] used in the treatment of epilepsy. It is used to treat partial seizures [2][3] (with and without generalization) in adults and partial and generalized seizures associated with Lennox-Gastaut syndrome in children. However, an increased risk of potentially fatal aplastic anemia and/or liver failure limit the drugs usage to severe refractory epilepsy.

Contents

Mechanism of action

As with most anticonvulsants, the precise mechanism is unknown.

It has an effect on GABA receptor binding sites.[4]

It may also work as a NMDA receptor antagonist.[5]

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.[6] 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.[7] 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, nausea, dizziness, somnolence, and headache. Many patients report increased alertness with the drug. Two rare but very serious effects include aplastic 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 of CYP2C19, an isoenzyme of the cytochrome P450 system involved in the metabolism of several commonly used medications.[8] Felbamate interacts with several other AEDs, including phenytoin, valproate, and carbamazepine; 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 of carbamazepine.[9]

References

  1. ^ Rho JM, Donevan SD, Rogawski MA (March 1997). "Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate". J. Pharmacol. Exp. Ther. 280 (3): 1383–91. PMID 9067327. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9067327. 
  2. ^ Leppik IE, Dreifuss FE, Pledger GW, et al. (November 1991). "Felbamate for partial seizures: results of a controlled clinical trial". Neurology 41 (11): 1785–9. PMID 1944909. 
  3. ^ Devinsky O, Faught RE, Wilder BJ, et al. (March 1995). "Efficacy of felbamate monotherapy in patients undergoing presurgical evaluation of partial seizures". Epilepsy Res. 20 (3): 241–6. PMID 7796796. http://linkinghub.elsevier.com/retrieve/pii/092012119400084A. 
  4. ^ Kume A, Greenfield LJ, Macdonald RL, Albin RL (June 1996). "Felbamate inhibits [3Ht-butylbicycloorthobenzoate (TBOB) binding and enhances Cl- current at the gamma-aminobutyric AcidA (GABAA) receptor]". J. Pharmacol. Exp. Ther. 277 (3): 1784–92. PMID 8667250. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8667250. 
  5. ^ Prous Science: Molecule of the Month January 2005
  6. ^ "www.fda.gov". http://www.fda.gov/bbs/topics/NEWS/NEW00488.html. Retrieved 2008-11-15. 
  7. ^ "www.fda.gov". http://www.fda.gov/bbs/topics/ANSWERS/ANS00605.html. Retrieved 2008-11-15. 
  8. ^ Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. http://medicine.iupui.edu/flockhart/table.htm.  Retrieved on December 25, 2008.
  9. ^ Curry WJ, Kulling DL (February 1998). "Newer antiepileptic drugs: gabapentin, lamotrigine, felbamate, topiramate and fosphenytoin". Am Fam Physician 57 (3): 513–20. PMID 9475899. http://www.aafp.org/afp/980201ap/curry.html. 

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Neurological Disorder. Gale Encyclopedia of Neurological Disorders. Copyright © 2005 by The Gale Group, Inc. All rights reserved.  Read more
Veterinary Dictionary. Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved.  Read more
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