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Pharmacologic class: Iminostilbene derivative
Therapeutic class: Anticonvulsant
Pregnancy risk category D
FDA Box Warning
• Prescriber should be thoroughly familiar with prescribing information, particularly regarding use with other drugs (especially those that increase toxicity potential).
• Drug has been linked to aplastic anemia and agranulocytosis.
• Transient or persistent decreases in platelet or white blood cell (WBC) counts have occurred, but data aren't available to accurately estimate incidence or outcome. Rarely, leukopenia cases progressed to aplastic anemia or agranulocytosis.
• Obtain complete pretreatment hematologic tests as baseline. If WBC or platelet count drops during therapy, monitor closely. Consider withdrawing drug if evidence of significant bone marrow depression develops.
Unclear. Chemically related to tricyclic antidepressants (TCAs). Anticonvulsant action may result from reduction in polysynaptic responses and blocking of post-tetanic potentiation.
Capsules (extended-release): 100 mg, 200 mg, 300 mg
Oral suspension: 100 mg/5 ml
Tablets: 200 mg
Tablets (chewable): 100 mg
Tablets (extended-release): 100 mg,
200 mg, 400 mg
Indications and dosages
➣ Prophylaxis of generalized tonic-clonic, mixed, and complex-partial seizures
Adults and children ages 12 and older: Initially, 200 mg P.O. b.i.d. (tablets) or 100 mg q.i.d. (oral suspension). Increase by up to 200 mg/day q 7 days until therapeutic blood levels are reached. Usual maintenance dosage is 600 to 1,200 mg/day in divided doses q 6 to 8 hours. In children ages 12 to 15, don't exceed 1 g/day. Give extended-release forms b.i.d.
Children ages 6 to 12: Initially, 100 mg P.O. b.i.d. (tablets) or 50 mg q.i.d. (oral suspension). Increase by up to 100 mg weekly until therapeutic levels are reached. Usual maintenance dosage is 400 to 800 mg/day. Don't exceed 1 g/day. Give extended-release forms b.i.d.
Children younger than age 6: Initially, 10 to 20 mg/kg/day P.O. in two or three divided doses. May increase by up to 100 mg/day at weekly intervals. Usual maintenance dosage is 250 to 350 mg/day. Don't exceed 400 mg/day.
➣ Trigeminal neuralgia
Adults: Initially, 100 mg b.i.d. (tablets) or 50 mg q.i.d. (oral suspension). Increase by up to 200 mg/day until pain relief occurs; then give maintenance dosage of 200 to 1,200 mg/day in divided doses. Usual maintenance range is 400 to 800 mg/day.
• Alcohol, cocaine, or benzodiazepine withdrawal
• Atypical psychoses
• Central diabetes insipidus
• Mood disorders
• Neurogenic pain
• Hypersensitivity to drug or TCAs
• MAO inhibitor use within past 14 days
• Bone marrow depression
• Pregnancy or breastfeeding
Use cautiously in:
• cardiac disease, hepatic disease, increased intraocular pressure, mixed seizure disorders, glaucoma
• elderly males with prostatic hypertrophy
• psychiatric patients.
• Don't give within 14 days of MAO inhibitor.
• Give tablets with meals; may give extended-release capsules without regard to meals.
• Don't give with grapefruit juice.
• If desired, contents of extended-release capsules may be sprinkled over food; however, capsule and contents shouldn't be crushed or chewed.
CNS: ataxia, drowsiness, fatigue, psychosis, syncope, vertigo, headache, worsening of seizures
CV: hypertension, hypotension, arrhythmias, atrioventricular block, aggravation of coronary artery disease, heart failure
EENT: blurred vision, diplopia, nystagmus, corneal opacities, conjunctivitis, pharyngeal dryness
GI: nausea, vomiting, diarrhea, abdominal pain, stomatitis, glossitis, dry mouth, anorexia
GU: urinary hesitancy, retention, or frequency; albuminuria; glycosuria; erectile dysfunction
Hematologic: eosinophilia, lymph-adenopathy, agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia
Metabolic: syndrome of inappropriate antidiuretic hormone secretion
Skin: photosensitivity, rash, urticaria, diaphoresis, erythema multiforme, Stevens-Johnson syndrome
Other: weight gain, chills, fever
Drug-drug. Acetaminophen: increased risk of acetaminophen-induced hepatotoxicity, decreased acetaminophen efficacy
Anticoagulants, bupropion: increased metabolism of these drugs, causing decreased efficacy
Barbiturates: decreased barbiturate blood level, increased carbamazepine blood level
Charcoal: decreased carbamazepine absorption
Cimetidine, danazol, diltiazem: increased carbamazepine blood level
Cyclosporine, felbamate, felodipine, haloperidol: decreased blood levels of these drugs
Doxycycline: shortened doxycycline half-life and reduced antimicrobial effect
Hormonal contraceptives: decreased contraceptive efficacy, possibly leading to pregnancy
Hydantoins: increased or decreased hydantoin blood level, decreased carbamazepine blood level
Isoniazid: increased risk of carbamazepine toxicity and isoniazid hepatotoxicity
Lithium: increased risk of CNS toxicity Macrolide antibiotics (such as clarithromycin and erythromycin), propoxy-phene, selective serotonin reuptake inhibitors (such as fluoxetine and flu-voxamine), verapamil: increased carbamazepine blood level, greater risk of toxicity
MAO inhibitors: high fever, hypertension, seizures, and possibly death
Nondepolarizing neuromuscular blockers: shortened carbamazepine duration of action
TCAs: increased carbamazepine blood level and greater risk of toxicity, decreased TCA blood level
Valproic acid: decreased valproic acid blood level with possible loss of seizure control, variable changes in carbamazepine blood level
Drug-diagnostic tests. Blood urea nitrogen, eosinophils, liver function tests: increased values
Granulocytes, hemoglobin, platelets, thyroid function tests, white blood cells: decreased values
Drug-food. Grapefruit juice: increased drug blood level and effects
Drug-herbs. Plantain (psyllium seed): inhibited GI absorption of drug
☞ Monitor patient closely. Institute seizure precautions if drug must be withdrawn suddenly.
• Assess for history of psychosis; drug may activate symptoms.
• Monitor baseline hematologic, kidney, and liver function test results.
• During dosage adjustments, monitor vital signs and fluid intake and output. Stay alert for fluid retention, renal failure, and cardiovascular complications.
• With high doses, monitor CBC weekly for first 3 months and then monthly to detect bone marrow depression.
• Tell patient that he may sprinkle contents of extended-release capsules over food, but that he shouldn't crush or chew capsule or contents.
• Advise patient that coating on extended-release capsules may be visible in stools because it isn't absorbed.
• Tell patient to take drug with meals to minimize GI upset.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, alertness, and vision.
• Advise patient to avoid excessive sun exposure and to wear protective clothing and sunscreen.
• Inform female patient that drug may interfere with hormonal contraception. Advise her to use alternative birth-control method.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above.
carbamazepineAn anticonvulsant used to manage partial seizures and generalised tonic-clonic seizures in children, bipolar disorder and trigeminal neuralgia; in contrast to valproate, carbamazepine is associated with better seizure control, fewer seizures and longer time to first seizure.
Dizziness, drowsiness, unsteadiness, nausea, vomiting, myelosuppression (up to 8-fold increase) in aplastic anaemia and agranulocytosis, rash, hair loss.