carbamazepine
Atretol, Carbatrol, Epitol, Tegretol, Tegretol-XR, Teril

Available forms
Available by prescription only
Capsules (extended-release): 200 mg, 300 mg
Oral suspension: 100 mg/5 ml
Tablets: 200 mg
Tablets (chewable): 100 mg, 200 mg
Tablets (extended-release): 100 mg, 200 mg, 400 mg

Indications and dosages
 Generalized tonic-clonic, complex-partial, mixed seizure patterns. Adults and children older than age 12: 200 mg P.O. b.i.d., or 100 mg P.O. q.i.d. of suspension, on day 1. May increase at weekly intervals by 200 mg P.O. daily, in divided doses at 6- to 8-hour intervals. Adjust to minimum effective level when control is achieved; don’t exceed 1,000 mg daily in children ages 12 to 15, or 1,200 mg daily in those older than age 15. In rare instances, doses up to 1,600 mg daily have been used in adults.
 For extended-release capsules, initial dose is 200 mg P.O. b.i.d. Increase at weekly intervals by up to 200 mg daily until optimal response is obtained. Dose shouldn’t exceed 1,000 mg daily in children ages 12 to 15 and 1,200 mg daily in patients older than age 15. Some adult doses may be up to 1,600 mg daily. Maintenance dosage is usually 800 to 1,200 mg daily.
Children ages 6 to 12: Initially, 100 mg P.O. b.i.d., or 50 mg P.O. q.i.d. of suspension. Increase at weekly intervals by adding 100 mg P.O. daily, first using a t.i.d. schedule and then q.i.d. if necessary. Adjust dosage based on patient response. Generally, daily dose shouldn’t exceed 1,000 mg. Children taking total daily dose of immediate-release form of 400 mg or more may be converted to same total daily dose of extended-release capsules using a b.i.d. regimen.
Children younger than age 6: Initially, 10 to 20 mg/kg daily P.O. b.i.d. or t.i.d. as tablets or q.i.d. as suspension. Increase weekly to achieve optimal clinical response administered t.i.d. or q.i.d. There’s no recommendation for safe administration at doses of more than 35 mg/kg daily. If optimal clinical response hasn’t been achieved at a dose less than 35 mg/kg daily, check plasma levels to determine whether it’s within the therapeutic range.
 Oral loading dose for rapid seizure control. Adults and children age 12 and older: 8 mg/kg P.O. of oral suspension.
Children younger than age 12: 10 mg/kg P.O. of oral suspension.
 Bipolar affective disorder; intermittent explosive disorder ◇. Adults: Initially, 200 mg P.O. b.i.d.; increase, p.r.n., q 3 to 4 days. Maintenance dosage may range from 600 to 1,600 mg daily.
 Trigeminal neuralgia. Adults: 100 mg P.O. b.i.d. or 50 mg P.O. q.i.d. of suspension with meals on day 1. Increase by 100 mg q 12 hours or 50 mg q.i.d. for suspension until pain is relieved. Don’t exceed 1.2 g daily. Maintenance dosage is 200 to 1,200 mg P.O. daily. For extended-release capsules, 200 mg P.O. on day 1. Dosage may be increased by up to 200 mg daily q 12 hours, p.r.n., to achieve freedom from pain. Maintenance dosage is usually 400 to 800 mg daily.
 Chorea ◇. Children: 15 to 25 mg/kg P.O. daily.
 Restless leg syndrome ◇. Adults: 100 to 300 mg P.O. h.s.

Pharmacodynamics
Anticonvulsant action: Carbamazepine is chemically unrelated to other anticonvulsants, and its mechanism of action is unknown. The anticonvulsant activity appears principally to involve limitations of seizure propagation by reduction of posttetanic potentiation of synaptic transmissions.
Analgesic action: In trigeminal neuralgia, carbamazepine is a specific analgesic through its reduction of synaptic neurotransmission.

Pharmacokinetics
Absorption: Absorbed slowly from the GI tract.
Distribution: Distributed widely throughout body; it crosses the placental barrier and accumulates in fetal tissue. About 75% is protein-bound. Therapeutic serum levels in adults are 4 to 12 mcg/ml; nystagmus may occur at serum levels of more than 4 mcg/ml, and ataxia, dizziness, and anorexia may occur at serum levels of 10 mcg/ml or more. Serum levels may be misleading because an unmeasured active metabolite also can cause toxicity. Carbamazepine levels in breast milk approach 60% of serum levels. There’s poor correlation between plasma levels and dose in children.
Metabolism: Metabolized by the liver to an active metabolite. It also may induce its own metabolism; over time, higher doses are needed to maintain plasma levels. Half-life is initially 25 to 65 hours and 12 to 17 hours with multiple dosing.
Excretion: Excreted in urine (70%) and feces (30%).

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or tricyclic antidepressants, in those with history of previous bone marrow suppression, and in patients who have taken an MAO inhibitor within 14 days of therapy. Use cautiously in patients with mixed-type seizure disorders.

Interactions
Drug-drug. Cimetidine, danazol, diltiazem, fluoxetine, fluvoxamine, isoniazid, macrolides (such as erythromycin), propoxyphene, valproic acid, verapamil: May increase carbamazepine blood levels. Use cautiously.
Doxycycline, felbamate, haloperidol, hormonal contraceptives, phenytoin, theophylline, warfarin: May decrease blood levels of these drugs. Monitor patient for decreased effect.
Lithium: Increases CNS toxicity of lithium. Avoid use together.
MAO inhibitors: Increases depressant and anticholinergic effects. Don’t use together.
Phenobarbital, phenytoin, primidone: May decrease carbamazepine levels. Monitor patient for decreased effect.
Drug-herb. Plantain: May decrease absorption, decreasing effect. Discourage use together.
Psyllium seed: May inhibit GI absorption. Discourage use together.

Adverse reactions
CNS: dizziness, vertigo, drowsiness, fatigue, ataxia, worsening of seizures (usually in patients with mixed-type seizure disorders, including atypical absence seizures), confusion, headache, syncope, fever.
CV: heart failure, hypertension, hypotension, aggravation of coronary artery disease, arrhythmias, AV block.
EENT: conjunctivitis, dry mouth and pharynx, blurred vision, diplopia, nystagmus.
GI: nausea, vomiting, abdominal pain, diarrhea, anorexia, stomatitis, glossitis.
GU: urinary frequency, urine retention, impotence, albuminuria, glycosuria.
Hematologic: aplastic anemia, agranulocytosis, eosinophilia, leukocytosis, thrombocytopenia.
Hepatic: hepatitis.
Respiratory: pulmonary hypersensitivity.
Skin: rash, urticaria, excessive diaphoresis, erythema multiforme, Stevens-Johnson syndrome.
Other: chills, SIADH.

Effects on lab test results
• May increase BUN levels.
• May increase liver function test values and eosinophil count. May decrease thyroid function test values, hemoglobin, hematocrit, and granulocyte, WBC, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose may include irregular breathing, respiratory depression, tachycardia, blood pressure changes, shock, arrhythmias, impaired consciousness (ranging to deep coma), seizures, restlessness, drowsiness, psychomotor disturbances, nausea, vomiting, anuria, or oliguria.
 Treat overdose with repeated gastric lavage, especially if patient ingested alcohol concurrently. Oral charcoal and laxatives may hasten excretion. Carefully monitor vital signs, ECG, and fluid and electrolyte balance. Diazepam may control seizures but can exacerbate respiratory depression.

Special considerations
• Adjust drug dosage based on individual response.
• Chewable tablets are available for children.
• Other unlabeled uses include hypophyseal diabetes insipidus, certain psychiatric disorders, and management of alcohol withdrawal.
• For administering through a nasogastric tube, mix with an equal volume of diluent (D₅W or normal saline solution) and administer; then flush with 100 ml of diluent.
• Hematologic toxicity is rare but serious. Hematologic and liver functions must be checked.
• Periodic eye examinations are recommended.
Breast-feeding patients
• Significant amounts of drug appear in breast milk; an alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Safety and efficacy haven’t been established for children younger than age 6 in daily doses higher than 35 mg/kg.
Geriatric patients
• Drug may activate latent psychosis, confusion, or agitation in elderly patients; use with caution.

Patient education
• Remind patient to store drug in a cool, dry place, and not in the medicine cabinet. Reduced bioavailability has been reported with use of improperly stored tablets.
• Tell patient that drug may cause GI distress. Patient should take drug with food at equally spaced intervals.
• Warn patient not to stop drug abruptly.
• Encourage patient to promptly report unusual bleeding, bruising, jaundice, dark urine, pale stools, abdominal pain, impotence, fever, chills, sore throat, mouth ulcers, edema, or disturbances in mood, alertness, or coordination.
• Warn patient that drug may cause drowsiness, dizziness, and blurred vision. Patient should avoid hazardous activities that require alertness, especially during first week of therapy and when dosage is increased.
• Remind patient to shake suspension well before using.
• Tell patient that the Carbatrol capsule can be opened and its contents sprinkled over food (such as a teaspoon of applesauce), but the capsule or its contents should never be crushed or chewed.
• Emphasize importance of follow-up laboratory tests and continued medical supervision.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use