Carbamazepine
Carbamazepine
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 antiseizure 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 be cautioned about operating dangerous machinery or driving a car until the drug’s effects can be fully evaluated.
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 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 and 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 will not be effective in preventing pregnancy. Some physicians recommend that a different
KEY TERMS
Absence seizure —An epileptic seizure characterized by a sudden, momentary loss of consciousness, occasionally accompanied by some minor, jerky movements in the neck or upper arms, a twitching of the face, or a loss of muscle tone.
Aplastic anemia —A form of anemia in which the bone marrow does not produce adequate amounts of peripheral blood components such as red cells, white cells, and platelets.
Bipolar disorder —A mental disorder characterized by dramatic and sometimes rapid mood swings, resulting in both manic and depressive episodes; formerly called manic-depressive disorder.
Convulsion —A violent, involuntary contraction or series of contractions of muscles.
Grand mal seizure —A seizure characterized by a sudden loss of consciousness that is immediately followed by generalized convulsions. Such a seizure is usually preceded by a sensory experience, called an aura, which provides a warning as to an impending convulsion.
Psychomotor seizure —A seizure characterized by electrical activity that is characterized by variable degrees of loss of consciousness and often accompanied by bizarre behavior.
method of contraception be used while carbamazepine is being taken.
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
El-Mallakh, Rif S. “Lithium and Antiepileptic Drugs in Bipolar Depression.” Bipolar Depression: A Comprehensive Guide. Washington, D.C.: American Psychiatric Publishing, 2006: 147–66.
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.
Preston, John D., John H. O’Neal, and Mary C. Talaga. Handbook of Clinical Psychopharmacology for Therapists, 4th ed. Oakland, CA: New Harbinger Publications, 2004.
PERIODICALS
Bowden, Charles L., and Nancy U. Karren. “Anticonvul-sants in Bipolar Disorder.” Australian and New Zealand Journal of Psychiatry 40.5 (May 2006): 386–93.
Cepeda, M. Soledad, and John T. Farrar. “Economic Evaluation of Oral Treatments for Neuropathic Pain.” Journal of Pain 7.2 (Feb. 2006): 119–28.
DeBattista, Charles, and Alan F. Schatzberg. “Psychotropic Dosing and Monitoring Guidelines.” Primary Psychiatry 13.6 (June 2006): 61–81.
El-Mallakh, Rif, Richard H. Weisler, Mark H. Townsend, and Lawrence D. Ginsberg. “Bipolar II Disorder: Current and Future Treatment Options.” Annals of Clinical Psychiatry 18.4 (Oct.–Dec. 2006): 259–66.
Gamble, C., P. R. Williamson, D. W. Chadwick, and A. G. Marson. “A Meta-Analysis of Individual Patient Responses to Lamotrigine or Carbamazepine Mono-therapy.” Neurology 66.9 (May 2006): 1310–17.
Gayatri, N. A., and, J. H. Livingston. “Aggravation of Epilepsy by Anti-Epileptic Drugs.” Developmental Medicine and Child Neurology 48.5 (May 2006): 394–98.
Ginsberg, Lawrence D. “Carbamazepine Extended-Release Capsules Use in Bipolar Disorder: Efficacy and Safety in Adult Patients.” Annals of Clinical Psychiatry 18 (Supplement 1) (May 2006): 9–14.
Ginsberg, Lawrence D. “Outcomes and Length of Treatment with Carbamazepine Extended-Release Capsules in Bipolar Disorder.” Annals of Clinical Psychiatry 18 (Supplement 1) (May 2006): 15–18.
Ginsberg, Lawrence D. “Predictors of Response to Carba-mazepine ExtendedRelease Capsules Treatment in Bipolar Disorder.” Annals of Clinical Psychiatry 18 (Supplement 1) (May 2006): 23–26.
Ginsberg, Lawrence D. “Safety of Carbamazepine Extended-Release Capsules in Bipolar Disorder Poly-pharmacy.” Annals of Clinical Psychiatry 18 (Supplement 1) (May 2006): 19–22.
Nasrallah, Henry A., Terence A. Ketter, and Amir H. Kalali. “Carbamazepine and Valproate for The Treatment of Bipolar Disorder: A Review of the Literature.” Journal of Affective Disorders 95.1–3 (Oct. 2006): 69–78.
Zhang, Zhang-Jin, and others. “Adjunctive Herbal Medicine with Carbamazepine for Bipolar Disorders: A Double-Blind, Randomized, Placebo-Controlled Study.” Journal of Psychiatric Research 41.3–4 (2007): 360–69.
OTHER
American Academy of Clinical Toxicology. 777 East Park Drive, P.O. 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., MD, Dr.P.H.
Ruth A. Wienclaw, PhD
Carbamazepine
Carbamazepine
Definition
Carbamazepine is an antiepileptic drug used to reduce or suppress seizures . The medication is also commonly prescribed to relieve certain neurogenic pain such as trigeminal neuralgia . This drug decreases abnormal electrical impulses through nerve cell pathways by inhibiting the activity of sodium channels in neurons. Consequently, it blocks the repetitive impulses that trigger seizures. In the United States, brand names for carbamazepine include Tegretol, Carbatrol, and Epitol. This medication is classified into the following categories: anticonvulsant, antimanic, and antineuralgic.
Purpose
Due to its high efficacy, carbamazepine is in many cases a first-line treatment for epilepsy , and is also frequently prescribed to treat acute neuralgias such as trigeminal neuralgia. Sometimes the drug is also used to improve bipolar disorder symptoms, especially during the manic phase of this disease.
Description
Carbamazepine is a lipid-soluble substance metabolized in the liver by enzymes of the P-450 family and therefore, its chronic administration may induce liver toxicity, especially in patients with reduced liver function. In contrast, persons whose P-450 enzymes are very efficient and metabolize the drug rapidly tend to have decreased carbamazepine half-life and therefore, reduced efficacy of the medication. The body slowly absorbs carbamazepine and the drug easily passes through the blood-brain barrier. It is rapidly transported into the central nervous system (CNS), where it exerts a depressant effect.
Recommended dosage
For treatment of seizures, the usual initial dose of carbamazepine for adults and children over 12 years of age is 200 milligrams, taken twice daily. The prescribing physician may increase the dosage in weekly intervals until optimum seizure control is achieved. Dosages generally do not exceed a range of 1000–1200 milligrams (mg) per day. For the treatment of trigeminal neuralgia, daily dosages usually range from 800–1200 mg per day during the stage of acute pain and 400–800 mg per day for preventative therapy.
Precautions
The ingestion of alcoholic drinks during carbamazepine therapy is contraindicated because both substances may potentiate (increase) the effects of the other. Other depressants of the central nervous system such as antihistamines, analgesic drugs, muscle relaxants, and tranquilizers, are also potentiated when used with carbamazepine or other antiepileptic medications. Diabetic patients should be monitored during the administration of this drug since it interferes with glucose blood levels. The drug should not be taken during pregnancy due to the absence of safety clinical studies for pregnant women. Tests in animals have shown that carbamazepine causes developmental defects in embryos when administered in high doses. As the drug is found in breast milk, the use of this medication is also contraindicated during breast-feeding. Carbamazepine may interfere with several biomarkers used in medical laboratory tests, and persons taking the medication should report its intake before blood or urine samples are collected for analysis.
Side effects
The intensity of side effects (or adverse effects) of carbamazepine is dose-dependant. Among the mild adverse effects observed during chronic administration of this medication are drowsiness, vertigo, fatigue , blurred vision, gastritis, constipation, aching muscles or joints, skin sensitivity to solar radiation , loss of appetite, and dry mouth. In most patients, these side effects are mild and tend to decrease in intensity or to completely disappear within a few days of treatment. However, if they are particularly intense or do persist for two or more weeks they should be reported to the physician.
Nevertheless, elderly patients or patients exhibiting one or more severe symptoms in association with carbamazepine intake such as chest pain, blurred vision, mental confusion or hallucinations, numbness, tachycardia, depression or marked mood changes, urinary retention or excessive diuresis, peripheral edema, severe diarrhea or vomiting, should report such symptoms to their physicians as soon as possible.
Moreover, immediate medical attention may be required in the presence of one or more of the following adverse effects: presence of blood in the urine or urine with a dark color, black tarry stools or pale stools, unusual bleeding or bruising, skin rashes, ulcers or white spots in the mouth or lips, chills and fever, shallow or uneasy breathing or wheezing chest, jaundice, arrhythmia, sudden blood pressure fall or unusual high blood pressure, cough and/or sore throat. These side effects could indicate the presence of a potentially serious blood disorder.
Interactions
The use of carbamazepine reduces the effectiveness of oral contraceptives and also reduces the effects of corticosteroids. The concomitant use of one of the following drugs inhibits the metabolism of carbamazepine, thereby decreasing its effectiveness: cimetidine, erythromycin, isoniazid, diltiazem, and propoxyphene. Conversely, carbamazepine decreases the plasma levels of phenytoin, another antiepileptic drug. Clarithromycin, an antibiotic, increases the blood levels of carbamazepine and thus, increases the risk of adverse effects.
The use of particular antidepressant medicines known as monoamine oxidase (MAO) inhibitors during carbamazepine therapy, or within the previous two weeks before initiating carbamazepine therapy may increase the risk of fever, severe high blood pressure, stroke , and convulsions. Therefore, an interval of at least two weeks is recommended between the administration of these two classes of drugs.
Resources
BOOKS
Champe, Pamela C., and Richard A. Harvey, eds. Pharmacology, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2000.
OTHER
"Carbamazepine." Medline Plus. National Library of Medicine. (January 1, 2003) (March 20, 2004). <http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682237.html>.
National Institute of Neurological Disorders and Stroke. NINDS Trigeminal Neuralgia Information Page. (May 29, 2001) (March 20, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/trigemin_doc.htm>.
ORGANIZATIONS
Epilepsy Foundation. 4351 Garden City Drive, Landover, MD 20785-7223. (800) 332-1000. <http://www.epilepsyfoundation.org>.
National Institute of Neurological Disorders and Stroke. P.O. Box 5801, Bethesda, MD, 20892-2540. (301) 496-5751 or (800) 352-9424. <http://www.ninds.nih.gov/>. contact_us.htm> or <http://www.ninds.nih.gov/index.htm>.
Sandra Galeotti
Carbamazepine
Carbamazepine
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.
Carbamazepine
Carbamazepine
Definition
Carbamazepine (Tegretol, Carbatrol) may be administered to cancer patients as a pain medicine.
Purpose
Carbamazepine is given to cancer patients primarily as a pain medication. The drug may, for example, be prescribed for stabbing pain that moves along a nerve. For noncancer patients, it is often used to treat epilepsy or bioplar disorder (manic-depressive illness).
Description
Carbamazepine suppresses some of the activities of the nerves. It does this by delaying the amount of time it takes for certain passageways in the nerves to recover after they have sent out a message.
Recommended dosage
Carbamazepine comes in several forms. There are 200 mg tablets, 100 mg chewable tablets, and a liquid containing 20 mg per milliliter that may be swallowed. There are extended-release tablets of carbamazepine containing 100, 200, or 400 mg and extended release capsules of the medication containing 200 and 300 mg.
Some authorities recommend starting with 100 to 200 mg twice a day. This strategy helps to minimize side effects. Then, the dose may be gradually increased every week. Adults may eventually receive 600 to 1200 mg a day, while 20 to 30 mg per kg of body weight per day is appropriate for children.
Side effects
Carbamazepine may exhibit side effects to the nervous system, for example, drowsiness, dizziness, blurred vision, unsteadiness, depression , impaired concentration, and headache. Patients should be cautious about operating machinery or performing tasks requiring alertness until tolerant of the side effects. After several weeks of treatment, these side effects may disappear. To minimize these side effects, doctors may start carbamazepine at a low dose and may recommend that it be taken before bedtime. As carbamazepine may cause stomach upset and nausea, the medicine should be taken with meals.
Effects of carbamazepine may include bone marrow suppression, which involves a low white blood cell and platelet count, but this is usually not severe. Very rarely, a dangerous anemia may occur during carbamazepine therapy. Blood counts should be monitored for patients using this drug. Some patients with previously diagnosed depression of the bone marrow should not be given carbamazepine.
Carbamazepine may cause birth defects and should be avoided in women who are pregnant. An appropriate contraceptive method should be used while on carbamazepine. Carbamazepine can cross into breast milk and should be avoided in women who are breastfeeding. Carbamazepine may also cause rash or sensitivity to the sun.
Interactions
Carbamazepine may affect the activity of other medicines, for example, oral contraceptives, warfarin , theophylline, doxycycline, haloperidol, corticosteroids , valproate, clonazepam, ethosuximide, lamotrigine, felbamate, and thyroid hormones. Oral contraceptives may become less effective if a patient is taking carbamazepine. Some doctors recommend that the form of birth control pill be altered or that a different method of contraception be used. If phenytoin and phenobarbital are taken at the same time as carbamazepine, the capacity of carbamazepine to interact with additional medications may increase. Side effects may occur if a patient is taking carbamazepine and one of the following medications simultaneously: danazol , dextropropoxyphene, erythromycin, clarithromycin, isoniazid, verapamil, or diltiazem. Due to the numerous potential of interactions with other drugs, patients should consult with their physician or pharmacist prior to starting any new medications either bought over the counter or initiated by another physician. Patients taking carbamazepine should not drink grapefruit juice.
Bob Kirsch
KEY TERMS
Bone marrow
—The spongy tissue found in the large bones of the body.
Trigeminal neuralgia
—A nerve problem associated with pain.