Yes

Anticonvulsant, Miscellaneous

Epilepsy:

Partial seizures with complex symptomatology (psychomotor, temporal lobe)

Generalized tonic-clonic seizures (grand mal)

Mixed seizure patterns

Pain relief of trigeminal neuralgia

Unlabeled uses: Treat bipolar disorders and other affective disorders, resistant schizophrenia, alcohol withdrawal, restless leg syndrome, psychotic behavior associated with dementia, post-traumatic stress disorders

D

Clinical effects on the fetus: Crosses the placenta. Dysmorphic facial features, cranial defects, cardiac defects, spina bifida, IUGR, and multiple other malformations reported. Epilepsy itself, number of medications, genetic factors, or a combination of these probably influence the teratogenicity of anticonvulsant therapy. Benefit:risk ratio usually favors continued use during pregnancy and breast-feeding.

Breast-feeding/lactation: Crosses into breast milk. American Academy of Pediatrics considers compatible with breast-feeding.

Hypersensitivity to carbamazepine or any component; may have cross-sensitivity with tricyclic antidepressants; marrow depression; MAO inhibitor use; pregnancy (may harm fetus)

MAO inhibitors should be discontinued for a minimum of 14 days before carbamazepine is begun; administer with caution to patients with history of cardiac damage or hepatic disease; potentially fatal blood cell abnormalities have been reported following treatment; early detection of hematologic change is important; advise patients of early signs and symptoms including fever, sore throat, mouth ulcers, infections, easy bruising, petechial or purpuric hemorrhage; carbamazepine is not effective in absence, myoclonic or akinetic seizures; exacerbation of certain seizure types have been seen after initiation of carbamazepine therapy in children with mixed seizure disorders. Elderly may have increased risk of SIADH-like syndrome.

Cardiovascular: Edema, congestive heart failure, syncope, bradycardia, hypertension or hypotension, A-V block, arrhythmias, thrombophlebitis, thromboembolism, lymphadenopathy

Central nervous system: Sedation, dizziness, fatigue, ataxia, confusion, headache, slurred speech

Dermatologic: Rash, urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome, photosensitivity reaction, alterations in skin pigmentation, exfoliative dermatitis, erythema multiforme, purpura, alopecia

Endocrine & metabolic: Hyponatremia, SIADH, fever, chills

Gastrointestinal: Nausea, vomiting, gastric distress, abdominal pain, diarrhea, constipation, anorexia, pancreatitis

Genitourinary: Urinary retention, urinary frequency, azotemia, renal failure, impotence

Hematologic: Aplastic anemia, agranulocytosis, eosinophilia, leukopenia, pancytopenia, thrombocytopenia, bone marrow suppression, acute intermittent porphyria, leukocytosis

Hepatic: Hepatitis, abnormal liver function tests, jaundice

Neuromuscular & skeletal: Peripheral neuritis

Ocular: Blurred vision, nystagmus, lens opacities, conjunctivitis

Otic: Tinnitus, hyperacusis

Miscellaneous: Hypersensitivity, diaphoresis

Symptoms of overdose include dizziness ataxia, drowsiness, nausea, vomiting, tremor, agitation, nystagmus, urinary retention, dysrhythmias, coma, seizures, twitches, respiratory depression, neuromuscular disturbances

Provide general supportive care. Activated charcoal is effective at binding certain chemicals and this is especially true for carbamazepine; other treatment is supportive/symptomatic. Treatment consists of inducing emesis or gastric lavage. EKG should also be monitored to detect cardiac dysfunction. Monitor blood pressure, body temperature, pupillary reflexes, bladder function for several days following ingestion.

CYP2C8 and 3A3/4 enzyme substrate; CYP1A2, 2C, and 3A3/4 inducer

Carbamazepine may induce the metabolism of benzodiazepines, citalopram, clozapine, corticosteroids, cyclosporine, doxycycline, ethosuximide, felbamate, felodipine, haloperidol, mebendazole, methadone, oral contraceptives, phenytoin, tacrolimus, theophylline, thyroid hormones, tricyclic antidepressants, valproic acid, warfarin; monitor for altered response; dose adjustment may be needed

Cimetidine, clarithromycin, danazol, diltiazem, erythromycin, felbamate, fluoxetine, fluvoxamine, isoniazid, lamotrigine, metronidazole, propoxyphene, verapamil, fluconazole, itraconazole, and ketoconazole may inhibit hepatic metabolism of carbamazepine with resultant increase of carbamazepine serum concentrations and toxicity

CBZ may enhance hepatotoxic potential of acetaminophen

Neurotoxicity may result in patients receiving lithium and CBZ concurrently

Carbamazepine suspension is incompatible with chlorpromazine solution and thioridazine liquid. Schedule carbamazepine suspension at least 1-2 hours apart from other liquid medicinals.

In addition to anticonvulsant effects, carbamazepine has anticholinergic, antineuralgic, antidiuretic, muscle relaxant and antiarrhythmic properties; may depress activity in the nucleus ventralis of the thalamus or decrease synaptic transmission or decrease summation of temporal stimulation leading to neural discharge by limiting influx of sodium ions across cell membrane or other unknown mechanisms; stimulates the release of ADH and potentiates its action in promoting reabsorption of water; chemically related to tricyclic antidepressants

Onset of effect: Requires several days to reach steady-state concentrations

Absorption: Slowly absorbed from GI tract

Distribution: V_d: Neonates: 1.5 L/kg; Children: 1.9 L/kg; Adults: 0.59-2 L/kg

Protein binding: 75% to 90%; may be decreased in newborns

Metabolism: In the liver to active epoxide metabolite; induces liver enzymes to increase metabolism and shorten half-life over time

Bioavailability, oral: 85%

Half-life: Initial: 18-55 hours; Multiple dosing: Children: 8-14 hours; Adults: 12-17 hours

Time to peak serum concentration: Unpredictable, within 4-8 hours

Elimination: 1% to 3% excreted unchanged in urine

Oral (dosage must be adjusted according to patient's response and serum concentrations):

<6 years: Initial: 5 mg/kg/day; dosage may be increased every 5-7 days to 10 mg/kg/day; then up to 20 mg/kg/day if necessary; administer in 2-4 divided doses/day

6-12 years: Initial: 100 mg twice daily or 10 mg/kg/day in 2 divided doses; increase by 100 mg/day at weekly intervals depending upon response; usual maintenance: 20-30 mg/kg/day in 2-4 divided doses/day; maximum dose: 1000 mg/day

Children >12 years and Adults: 200 mg twice daily to start, increase by 200 mg/day at weekly intervals until therapeutic levels achieved; usual dose: 800-1200 mg/day in 3-4 divided doses; some patients have required up to 1.6-2.4 g/day

Dosing adjustment in renal impairment: Cl_cr <10 mL/minute: Administer 75% of dose

Food: Drug may cause GI upset, take with large amount of water or food to decrease GI upset. May need to split doses to avoid GI upset.

Sodium: SIADH and water intoxication; monitor fluid status; may need to restrict fluid

Timing of serum samples: Absorption is slow, peak levels occur 6-8 hours after ingestion of the first dose; the half-life ranges from 8-60 hours, therefore, steady-state is achieved in 2-5 days

Therapeutic levels: 6-12 mg/mL (SI: 25-51 mmol/L)

Toxic concentration: >15 mg/mL; patients who require higher levels of 8-12 mg/mL (SI: 34-51 mmol/L) should be watched closely. Side effects including CNS effects occur commonly at higher dosage levels. If other anticonvulsants are given therapeutic range is 4-8 mg/mL.

BUN, AST, ALT, bilirubin, alkaline phosphatase (S); calcium, T₃, T₄, sodium (S)

No information available to require special precautions

Some patients may experience sore throat or mouth ulcers

Take exactly as directed (do not increase dose or frequency or discontinue without consulting prescriber). While using this medication, do not use alcohol and other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, vomiting, loss of appetite, or dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Wear identification of epileptic status and medications. Report CNS changes, mentation changes, or changes in cognition; muscle cramping, weakness, tremors, changes in gait; persistent GI symptoms (cramping, constipation, vomiting, anorexia); rash or skin irritations; unusual bruising or bleeding (mouth, urine, stool); worsening of seizure activity, or loss of seizure control. Pregnancy precautions: Inform prescriber if you are or intend to be pregnant.

Observe patient for excessive sedation; suspension dosage form must be given on a 3-4 times/day schedule versus tablets which can be given 2-4 times/day

Capsule, extended release: 200 mg, 300 mg

Suspension, oral (citrus-vanilla flavor): 100 mg/5 mL (450 mL)

Tablet: 200 mg

Tablet, chewable: 100 mg

Tablet, extended release: 100 mg, 200 mg, 400 mg

Apfelbaum JD, Caravati EM, Kerns WP 2nd, et al, "Cardiovascular Effects of Carbamazepine Toxicity," Ann Emerg Med, 1995, 25(5):631-5.

Cooney GF, Mochon M, Kaiser B, et al, "Effects of Carbamazepine on Cyclosporine Metabolism in Pediatric Renal Transplant Recipients," Pharmacotherapy, 1995, 15(3):353-6.

Furst SM and Uetrecht JP, "The Effect of Carbamazepine and Its Reactive Metabolite 9-Acridine Carboxaldehyde, on Immune Cell Function In Vitro," Int J Immunopharmacol, 1995, 17(5):445-52.

Gary N, Byra W, Eisinger R, "Carbamazepine Poisoning: Treatment by Hemoperfusion," Nephron, 1981, 27(4-5):202-3.

Gilman JT, "Carbamazepine Dosing for Pediatric Seizure Disorders: The Highs and Lows," DICP, 1991, 25(10):1109-12.

Iwahashi IS, Miyatake R, Suwaki H, et al, "The Drug-Drug Interaction Effects of Haloperidol on Plasma Carbamazepine Levels," Clin Neuropharmacol, 1995, 18:233-6.

Jones KL, Lacro RV, Johnson KA, et al, "Pattern of Malformation in the Children of Women Treated With Carbamazepine During Pregnancy," N Engl J Med, 1989, 320(25):1661-6.

Keating A and Blahunka P, "Carbamazepine-Induced Stevens-Johnson Syndrome in a Child," Ann Pharmacother, 1995, 29(5):538-9.

Korinthenberg R, Haug C, and Hannak D, "The Metabolization of Carbamazepine to CBZ-10,11 Epoxide in Children From the Newborn Age to Adolescence," Neuropediatrics, 1994, 25(4):214-6.

Liu H and Delgado MR, "Influence of Sex, Age, Weight, and Carbamazepine Dose on Serum Concentrations, Concentration Ratios, and Level/Dose Ratios of Carbamazepine and Its Metabolites," Ther Drug Monit, 1994, 16(5):469-76.

Miles MV, Lawless ST, Tennison MB, et al, "Rapid Loading of Critically Ill Patients With Carbamazepine Suspension," Pediatrics, 1990, 86(2):263-6.

Montgomery VL, Richman BJ, Goldsmith LJ, et al, "Severity and Carbamazepine Level at Time of Initial Poison Center Contact Correlate With Outcome in Carbamazepine Poisoning," J Toxicol Clin Toxicol, 1995, 33(4):311-23.

Nilsson C, Sterner G, and Idvall J, "Charcoal Hemoperfusion for Treatment of Serious Carbamazepine Poisoning," Acta Med Scand, 1984, 216(1):137-40.

Patterson BD, "Possible Interaction Between Metronidazole and Carbamazepine," Ann Pharmacother, 1994, 28(11):1303-4.

Rispal P, Lasseur C, Labouyrie E, et al, "Pseudolymphoma-Induced by Carbamazepine. Report of Two Cases," Rev Med Interne, 1995, 16(3):214-8.

Stafstrom CE, Nohria V, Loganbill H, et al, "Erythromycin-induced Carbamazepine Toxicity: A Continuing Problem," Arch Pediatr Adolesc Med, 1995, 149(1):99-101.

Stremski ES, Brady WB, Prasad K, et al, "Pediatric Carbamazepine Intoxication," Ann Emerg Med, 1995, 25(5):624-30.

Tohen M, Castillo J, Baldessarini RJ, et al, "Blood Dyscrasias With Carbamazepine and Valproate: A Pharmacoepidemiological Study of 2,228 Patients at Risk," Am J Psychiatry, 1995, 152(3):413-8.

Wason S, Baker RC, Carolan P, et al, "Carbamazepine Overdose - The Effects of Multiple Doses of Activated Charcoal," J Toxicol Clin Toxicol, 1992, 30(1):39-48.

Zuber M, Elsasser S, Ritz R, et al, "Flumazenil (Anexate®) in Severe Intoxication With Carbamazepine (Tegretol®)," Eur Neurol, 1988, 28(3):161-3.