Carbamazepine



Carbamazepine 1007
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Definition

Carbamazepine is an anticonvulsant that is structurally related to tricyclic antidepressants such as amitriptyline and imipramine . In the United States, carbamazepine is sold under the trade names Tegretol and Carbatrol.

Purpose

Carbamazepine is effective in the treatment of psychomotor and grand mal seizures and a type of facial pain called trigeminal neuralgia and, in combination with other drugs, for psychiatric disorders such as mania and extreme aggression. Carbamazepine is also occasionally used to control pain in persons with cancer.

Description

Carbamazepine was first marketed as an anti-seizure medication and as a first-line treatment for trigeminal neuralgia. Because it was later noted to be effective in patients with certain psychiatric disorders, psychiatrists began combining it with other drugs such as lithium and major tranquilizers in severe cases of bipolar disease and aggressive behavior that could not be managed with single-drug therapy.

Carbamazepine is available in 100-mg chewable tablets, 200-mg capsules and a suspension at 100 mg per 5 ml of liquid.

Recommended dosage

When used to treat seizure disorders or psychiatric disease, the recommended initial dosage of carbamazepine is 200 mg two times each day. If needed, the daily dosage may be increased by 200 mg once each week. Total daily dosages should not exceed 1,000 mg in children between the ages of 12 and 15 years. Total daily dosages for adults should not exceed 1,200 mg. Carbamazepine should be taken with meals.

Precautions

Carbamazepine should be used with caution in persons who also experience other types of seizure disorders such as atypical absence seizures. Among such individuals, carbamazepine usage has been associated with an increased risk of initiating, rather than controlling, generalized convulsions.

Carbamazepine should never be discontinued abruptly unless another treatment for seizures is initiated at the same time. If this does not happen, acute withdrawal of carbamazepine may result in seizures.

Patients should be alert for signs and symptoms of bone marrow toxicity such as fever, sore throat, infection, mouth sores, easy bruising, or bleeding which occurs just under the skin.

Because carbamazepine may affect mental alertness, especially early in therapy, patients receiving this drug should not operate dangerous machinery or drive a car until they understand how the drug will affect them.

Side effects

The most commonly reported adverse reactions to carbamazepine include dizziness, drowsiness, unsteadiness, nausea and vomiting. These are more common when therapy is just beginning.

Carbamazepine has been reported to cause aplastic anemia. This is a form of anemia that is generally does not respond to treatment. The bone marrow of persons with aplastic anemia does not produce adequate amounts of red blood cells, white blood cells, and platelets. Blood counts should be monitored for individuals using this drug. Some people with previously diagnosed depression of the bone marrow should not take carbamazepine.

Carbamazepine may cause birth defects and should be avoided by women who are pregnant. An effective contraceptive method should be used while taking carbamazepine. It is important to note that this medication may decrease the effectiveness of oral contraceptives.

The drug can cross into breast milk and should be avoided by women who are breast-feeding.

Carbamazepine may also cause a skin rash or sensitivity to the sun.

Interactions

Blood levels of carbamazepine may be reduced when it is used in combination with other drugs such as phenobarbitol, phenytoin or primidone. This means that inadequate amounts of carbamazepine are available to the body, limiting the ability of the drug to control seizure activity or treat psychiatric disease. Carbamazepine also causes reductions in the blood levels of the following drugs when they are used simultaneously: phenytoin, warfarin, doxycycline, haloperidol , valproic acid , and theophylline.

The simultaneous administration of carbamazepine with erythromycin, cimetidine, propoxyohene, isoniacid, fluoxetine and calcium channel blockers such as nifedipine or verapamil may increase the blood level of carbamazepine to a toxic range.

The simultaneous use of carbamazepine and oral contraceptives may increase the possibility that the oral contraceptive won't be effective in preventing pregnancy. Some physicians recommend that a different method of contraception be used while carbamazepine is being used.

People taking carbamazepine should not drink grapefruit juice. Grapefruit juice slows the breakdown of carbamazepine, increasing the concentration of carbamazepine in the bloodstream.

Due to the potential of many interactions with other drugs, individuals should consult with a physician or pharmacist prior to starting any new medications either bought over the counter or initiated by another physician.

Resources

BOOKS

Adams, Michael and Norman Holland. Core Concepts in Pharmacology. Philadelphia: Lippincott-Raven, 1998.

Foreman, John C. and Torben Johansen. Textbook of Receptor Pharmacology. 2nd Ed. Boca Raton, FL: CRC Press, 2002.

Page, Clive P., and Michael Murphy. Integrated Pharmacology. St. Louis: Mosby-Year Book, 2002.

Von Boxtel, Chris J., Budiono Santoso, and I. Ralph Edwards. Drug Benefits and Risks: International Textbook of Clinical Pharmacology. New York: John Wiley and Sons, 2001.

PERIODICALS

Ferrier, I. N. "Developments in mood stabilisers." British Medical Bulletin 57 (2001): 179-192.

Muller-Oerlinghausen, B. A. Berghofer, and M. Bauer. "Bipolar disorder." Lancet 359, no. 9302 (2002): 241-247.

Spiller, H. A. "Management of carbamazepine overdose." Pediatric Emergency Care 17, No. 6 (2001): 452-456.

Steffens, D. C. and K. R. Krishnan. "Decision model for the acute treatment of mania." Depression and Anxiety 4, No. 6 (1996-97): 289-293.

Takahashi, H., K. Yoshida, H. Higuchi, and T. Shimizu. "Development of parkinsonian symptoms after discontinuation of carbamazepine in patients concurrently treated with risperidone: two case reports." Clinical Neuropharmacology 24, No. 6 (2001): 358-360.

OTHER

American Academy of Clinical Toxicology. 777 East Park Drive, PO Box 8820, Harrisburg, PA 17105-8820. Telephone: (717) 558-7750. Fax: (717) 558-7845. Web site: <http://www.clintox.org/index.html> .

American Psychiatric Association. 1400 K Street NW, Washington, DC 20005. Telephone: (888) 357-7924. Fax: (202) 682-6850. Web site: <http://www.psych.org/> .

American Society for Clinical Pharmacology and Therapeutics. 528 North Washington Street, Alexandria, VA 22314. Telephone: (703) 836-6981. Fax: (703) 836-5223.

American Society for Pharmacology and Experimental Therapeutics. 9650 Rockville Pike, Bethesda, MD 20814-3995. Telephone: (301) 530-7060. Fax: (301) 530-7061. Web site: <http://www.aspet.org/> .

L. Fleming Fallon, Jr., M.D., Dr.P.H.



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