critical benefit-to-risk appraisal in patients with a history of cardiac conduction disturbance, including second- and third-degree atrioventricular (AV) block; cardiac, hepatic, or renal damage; adverse hematologic or hypersensitivity reaction to other drugs including reactions to other anticonvulsants; or interrupted courses of therapy with carbamazepine May exacerbate absence seizures; in the event of allergic or hypersensitivity reaction, more rapid substitution of alternative therapy may be necessary Bipolar mania: Efficacy inconsistent; APA recommends use after failure of or if there is resistance to lithium and valproate May cause psychosis/confusion/agitation; elderly patients are at greater risk May render oral contraceptives ineffective Higher risk of potentially fatal skin reactions (SJS/TEN) in patients of Asian ancestry (genetic testing recommended); increased risk of developing hypersensitivity reactions with presence of HLAA*3101 or HLA-B*1502, inherited allelic variants of the HLA-A and HLA-B gene (see Pharmacogenomics in the Pharmacology section); Hyponatremia may occur and appears to be a result of SIADH; may be dose-related and elderly individuals are at greater risk Associated with hypotension, bradycardia, AV block, and signs and symptoms of HF Fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), reported Not a simple analgesic; do not use to relieve minor aches and pains Suspension formulation contains sorbitol; not for administration to patients with rare hereditary problems of fructose intolerance AV heart block, including second and third-degree block, reported following carbamazepine treatment; effect occurred generally, but not solely, in patients with underlying EKG abnormalities or risk factors for conduction disturbances Rare cases of anaphylaxis and angioedema involving larynx, glottis, lips, and eyelids reported with first or subsequent doses; angioedema associated with laryngeal edema can be fatal; if a patient develops reactions after treatment discontinue therapy and start alternative treatment; patients should not be rechallenged with drug Mild anticholinergic activity; use caution in patients with sensitivity to anticholinergic effects Fever and chills, decreased levels of plasma calcium leading to osteoporosis, and hyperammonemia reported Urinary frequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, renal failure, and impotence may occur; albuminuria, glycosuria, elevated BUN, and microscopic deposits in urine also reported; there have been rare reports of impaired male fertility and/or abnormal spermatogenesis Hepatic effects Hepatic effects reported ranging from slight elevations in liver enzymes to rare cases of hepatic failure In some cases, hepatic effects may progress despite discontinuation Rare instances of vanishing bile duct syndrome reported; consists of a variable clinical course ranging from fulminant to indolent, involving the destruction and disappearance of the intrahepatic bile ducts Some cases associated other immunoallergenic syndromes (eg, multiorgan hypersensitivity [DRESS syndrome], serious dermatologic reactions) DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy and/or facial swelling in association with other organ system involvement, such as hepatitis, nephritis, hematologic abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection As an example there has been a report of vanishing bile duct syndrome associated with Stevens-Johnson syndrome, and in another case an association with fever and eosinophilia Baseline and periodic evaluations of liver function, particularly in patients with history of liver disease, must be performed during treatment with this drug since liver damage may occur; drug should be discontinued immediately in cases of aggravated liver dysfunction or active liver disease Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), during pregnancy; encourage women who receive therapy during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry; this can be done by calling the toll-free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org, and must be done by the patient herself Females of reproductive potential should be counseled on consistent use of effective nonhormonal contraception or barrier methods during treatment Therapy can cause fetal harm when administered to a pregnant woman; an association between use of drug during pregnancy and congenital malformations, including spina bifida and malformations involving other body systems (e.g., craniofacial defects and cardiovascular malformations) shown; developmental delays reported Women of childbearing potential should be informed of potential risk to fetus Consideration should be given to discontinuing therapy in women who are pregnant or attempting to become pregnant if benefits of discontinuation outweigh risks of recurrent seizures; women with epilepsy should not discontinue therapy abruptly due to risk of status epilepticus and less severe seizures which may be life-threatening There have been a few cases of neonatal seizures and/or respiratory depression associated with maternal carbamazepine in combination with other antiepileptic drugs; a few cases of neonatal vomiting, diarrhea, and/or decreased feeding have also been reported in association with maternal carbamazepine use; these symptoms may represent a neonatal withdrawal syndrome Tests to detect birth defects using currently accepted procedures should be considered a part of routine prenatal care in childbearing women receiving carbamazepine; evidence suggests that folic acid supplementation prior to conception and during first trimester of pregnancy decreases risk for congenital neural tube defects in general population; not known whether risk of neural tube defects in offspring of women receiving therapy is reduced by folic acid supplementation, but dietary folic acid supplementation both prior to conception and during pregnancy should be recommended for patients in therapy Animal data In animal studies, therapy during pregnancy resulted in developmental toxicity, including increased incidences of fetal malformations Lactation Drug and its epoxide metabolite are excreted in human milk; there are no data to assess effects of drug or its metabolites on milk production, or on breastfed infant, of mothers taking drug; developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for drug and any potential adverse effects on the breastfed infant from drug or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Stabilizes inactivated state of sodium channels, thereby making neurons less excitable May reduce activity of nucleus ventralis of the thalamus or decrease synaptic transmission or summation of temporal stimulation leading to neuronal discharge Absorption Bioavailability: 85% (oral suspension) Peak serum time: 4.5 hr (immediate-release tablets); 3-12 hr (extended-release tablets); 1.5 hr (oral suspension) Distribution Protein bound: 75-90% Vd: 1.5 L/kg (neonates); 1.9 L/kg (children); 0.59-2 L/kg (adults) Metabolism Via hepatic CYP3A4 Metabolites: Carbamazepine 10,11-epoxide Enzymes induced: CYP1A2, CYP2C9, CYP3A4 Elimination Half-life: 25-65 hr (initial dosing); decreases to 10-20 hr after autoinduction; 35-40 hr (extended release) Excretion: Urine (72%); feces (28%) Pharmacogenomics HLA-B*1502 It is estimated that 1 in 20 patients with HLA-B*1502 will have a severe dermatologic reaction (eg, TEN, SJS) when taking carbamazepine This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais HLA-A*3101 Retrospective case-control studies in patients of European, Korean, and Japanese ancestry have found a moderate association between the risk of developing hypersensitivity reactions and the presence of HLAA*3101, an inherited allelic variant of the HLA-A gene, in patients using carbamazepine; these hypersensitivity reactions include Stevens Johnson syndrome and toxic epidermal necrolysis HLA-A*3101 is expected to be carried by more than 15% of patients of Japanese, Native American, Southern Indian (eg, Tamil Nadu) and some Arabic ancestry; up to about 10% in patients of Han Chinese, Korean, European, Latin American, and other Indian ancestry; and up to about 5% in African-Americans and patients of Thai, Taiwanese, and Chinese (Hong Kong) ancestry Genetic testing laboratories The following companies provide genetic testing for HLA variants Kashi Clinical Laboratories (www.kashilab.com) LabCorp (http://www.labcorp.com/) Specialty Laboratories (http://www.specialtylabs.com) Quest (http://www.questdiagnostics.com) Oral Administration Take with food Do not chew, crush, or cut extended-release tablets IV Preparation For IV use only Must be diluted with 100 mL of a compatible diluent before infusion (ie, 0.9% NaCl, lactated Ringer’s solution, or D%W) Transfer measured dose to 100 mL bag of compatible solution Inspected visually for particulate matter, cloudiness, or discoloration prior to administration; if any of these are present, discard the solution IV Administration Administer IV over 30 minutes Storage IV (before dilution) Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F) IV (after dilution) Controlled room temperature (20-25°C [68-77°F]): Maximum of 4 hr Refrigerated (2-8°C [36-46°F]): Maximum of 24 hr BRAND FORM. UNIT PRICE PILL IMAGE Tegretol oral- 200 mg tabletTegretol oral- 100 mg/5 mL suspensioncarbamazepine oral- 400 mg tabletcarbamazepine oral- 200 mg tabletcarbamazepine oral- 200 mg tabletcarbamazepine oral- 300 mg capsulecarbamazepine oral- 100 mg/5 mL suspensioncarbamazepine oral- 200 mg tabletcarbamazepine oral- 100 mg/5 mL suspensioncarbamazepine oral- 200 mg tabletcarbamazepine oral- 400 mg tabletcarbamazepine oral- 100 mg chewable tabletcarbamazepine oral- 200 mg capsulecarbamazepine oral- 200 mg/10 mL suspensioncarbamazepine oral- 300 mg capsulecarbamazepine oral- 200 mg tabletcarbamazepine oral- 200 mg tabletcarbamazepine oral- 100 mg chewable tabletcarbamazepine oral- 100 mg chewable tabletcarbamazepine oral- 200 mg tabletcarbamazepine oral- 100 mg capsulecarbamazepine oral- 400 mg tabletcarbamazepine oral- 100 mg tabletcarbamazepine oral- 200 mg tabletcarbamazepine oral- 100 mg capsulecarbamazepine oral- 100 mg tabletcarbamazepine oral- 200 mg tabletcarbamazepine oral- 100 mg tabletcarbamazepine oral- 100 mg/5 mL suspensioncarbamazepine oral- 200 mg tabletcarbamazepine oral- 100 mg tabletcarbamazepine oral- 100 mg capsulecarbamazepine oral- 200 mg capsulecarbamazepine oral- 200 mg capsulecarbamazepine oral- 300 mg capsuleTegretol XR oral- 400 mg tabletTegretol XR oral- 200 mg tabletTegretol XR oral- 100 mg tabletEpitol oral- 200 mg tabletCarbatrol oral- 300 mg capsuleCarbatrol oral- 100 mg capsuleCarbatrol oral- 200 mg capsuleCopyright © 2010 First DataBank, Inc.Print Patient Educationcarbamazepine oral CARBAMAZEPINE - ORAL (KAR-ba-MAZ-e-peen) COMMON BRAND NAME(S): Tegretol WARNING: Carbamazepine may rarely cause very serious (possibly fatal) skin reactions. Some people in certain ethnic groups (such as people of Asian/South Asian descent) are at greater risk. Your doctor may order a blood test to measure your risk before you start this medication. If the blood test shows you are at greater risk, your doctor should discuss the risks and benefits of carbamazepine and other treatment choices with you. Such skin reactions have developed mostly within the first few months of treatment. Get medical help right away if you develop any of the following symptoms: skin rash/blisters/peeling, itching, or swelling. Ask your doctor or pharmacist for more details.This drug has rarely caused very serious blood disorders (aplastic anemia, agranulocytosis). Your doctor will monitor your blood counts to minimize the chance of these side effects. Keep all medical and lab appointments. Get medical help right away if any of these rare but very serious side effects occur: signs of infection (such as sore throat that doesn't go away, fever, swollen lymph nodes), unusual weakness/tiredness, shortness of breath, or easy bleeding/bruising. USES: Carbamazepine is used to prevent and control seizures. This medication is known as an anticonvulsant or anti-epileptic drug. It is also used to relieve certain types of nerve pain (such as trigeminal neuralgia). This medication works by reducing the spread of seizure activity in the brain and restoring the normal balance of nerve activity. HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using carbamazepine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with food as directed by your doctor. If you are using the chewable tablets, chew the tablets thoroughly before swallowing.If you are using the suspension form of this medication, shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose. Separate doses of the suspension from other liquid medicines by at least 2 hours.The dosage is based on your medical condition and response to treatment. In children, the dosage is also based their weight. To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit