Carbatrol®, Tegretol®, Tegretol®-XR: Partial seizures with complex symptomatology (psychomotor, temporal lobe), generalized tonic-clonic seizures (grand mal), mixed seizure patterns, trigeminal neuralgia

Equetro™: Acute manic and mixed episodes associated with bipolar 1 disorder

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. Abrupt discontinuation is not recommended in patients being treated for seizures. Dizziness or drowsiness may occur; caution should be used when performing tasks which require alertness (operating machinery or driving) until the effects are known. Coadministration of carbamazepine and delavirdine may lead to loss of virologic response and possible resistance. Elderly may have increased risk of SIADH-like syndrome. Carbamazepine has mild anticholinergic activity; use with caution in patients with increased intraocular pressure (monitor closely), or sensitivity to anticholinergic effects (urinary retention, constipation). Severe dermatologic reactions, including Lyell and Stevens-Johnson syndromes, although rarely reported, have resulted in fatalities. Drug should be discontinued if there are any signs of hypersensitivity.

Cardiovascular: Arrhythmias, AV block, bradycardia, chest pain (bipolar use), CHF, edema, hyper-/hypotension, lymphadenopathy, syncope, thromboembolism, thrombophlebitis

Central nervous system: Amnesia (bipolar use), anxiety (bipolar use), aseptic meningitis (case report), ataxia (bipolar use 15%), confusion, depression (bipolar use), dizziness (bipolar use 44%), fatigue, headache (bipolar use 22%), sedation, slurred speech, somnolence (bipolar use 32%)

Dermatologic: Alopecia, alterations in skin pigmentation, erythema multiforme, exfoliative dermatitis, photosensitivity reaction, pruritus (bipolar use 8%), purpura, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Chills, fever, hyponatremia, syndrome of inappropriate ADH secretion (SIADH)

Gastrointestinal: Abdominal pain, anorexia, constipation, diarrhea, dyspepsia (bipolar use), gastric distress, nausea (bipolar use 29%), pancreatitis, vomiting (bipolar use 18%), xerostomia (bipolar use)

Genitourinary: Azotemia, impotence, renal failure, urinary frequency, urinary retention

Hematologic: Acute intermittent porphyria, agranulocytosis, aplastic anemia, bone marrow suppression, eosinophilia, leukocytosis, leukopenia, pancytopenia, thrombocytopenia

Hepatic: Abnormal liver function tests, hepatic failure, hepatitis, jaundice

Neuromuscular & skeletal: Back pain, pain (bipolar use 12%), peripheral neuritis, weakness

Ocular: Blurred vision, conjunctivitis, lens opacities, nystagmus

Otic: Hyperacusis, tinnitus

Miscellaneous: Diaphoresis, hypersensitivity (including multiorgan reactions, may include disorders mimicking lymphoma, eosinophilia, hepatosplenomegaly, vasculitis); infection (bipolar use 12%)

Acetaminophen: Carbamazepine may enhance hepatotoxic potential of acetaminophen; risk is greater in acetaminophen overdose

Antimalarial drugs (chloroquine, mefloquine): Concomitant use with carbamazepine may reduce seizure control by lowering plasma levels. Monitor.

Antipsychotics: Carbamazepine may enhance the metabolism (decrease the efficacy) of antipsychotics; monitor for altered response; dose adjustment may be needed

Barbiturates: May reduce serum concentrations of carbamazepine; monitor

Benzodiazepines: Serum concentrations and effect of benzodiazepines may be reduced by carbamazepine; monitor for decreased effect

Calcium channel blockers: Diltiazem and verapamil may increase carbamazepine levels, due to enzyme inhibition (see below); other calcium channel blockers (felodipine) may be decreased by carbamazepine due to enzyme induction

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

Corticosteroids: Metabolism may be increased by carbamazepine

Cyclosporine (and other immunosuppressants): Carbamazepine may enhance the metabolism of immunosuppressants, decreasing its clinical effect; includes both cyclosporine and tacrolimus.

CYP1A2 substrates: Carbamazepine may decrease the levels/effects of CYP1A2 substrates. Example substrates include aminophylline, estrogens, fluvoxamine, mirtazapine, ropinirole, and theophylline.

CYP2B6 substrates: Carbamazepine may decrease the levels/effects of CYP2B6 substrates. Example substrates include bupropion, efavirenz, promethazine, selegiline, and sertraline.

CYP2C8/9 substrates: Carbamazepine may decrease the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, losartan, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, sulfonamides, warfarin, and zafirlukast.

CYP2C19 substrates: Carbamazepine may decrease the levels/effects of CYP2C19 substrates. Example substrates include citalopram, diazepam, methsuximide, phenytoin, propranolol, proton pump inhibitors, sertraline, and voriconazole.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of carbamazepine. Example inducers include aminoglutethimide, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins. Carbamazepine may induce its own metabolism.

CYP3A4 inhibitors: May increase the levels/effects of carbamazepine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

CYP3A4 substrates: Carbamazepine may decrease the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, clarithromycin, cyclosporine, erythromycin, estrogens, mirtazapine, nateglinide, nefazodone, nevirapine, protease inhibitors, tacrolimus, and venlafaxine.

Danazol: May increase serum concentrations of carbamazepine; monitor

Doxycycline: Carbamazepine may enhance the metabolism of doxycycline, decreasing its clinical effect

Ethosuximide: Serum levels may be reduced by carbamazepine

Felbamate: May increase carbamazepine levels and toxicity (increased epoxide metabolite concentrations); carbamazepine may decrease felbamate levels due to enzyme induction

Immunosuppressants: Carbamazepine may enhance the metabolism of immunosuppressants, decreasing its clinical effect; includes both cyclosporine and tacrolimus

Isoniazid: May increase the serum concentrations and toxicity of carbamazepine; in addition, carbamazepine may increase the hepatic toxicity of isoniazid (INH)

Isotretinoin: May decrease the effect of carbamazepine

Lamotrigine: Increases the epoxide metabolite of carbamazepine resulting in toxicity; carbamazepine increases the metabolism of lamotrigine

Lithium: Neurotoxicity may result in patients receiving concurrent carbamazepine

Loxapine: May increase concentrations of epoxide metabolite and toxicity of carbamazepine

Methadone: Carbamazepine may enhance the metabolism of methadone resulting in methadone withdrawal

Methylphenidate: concurrent use of carbamazepine may reduce the therapeutic effect of methylphenidate; limited documentation; monitor for decreased effect

Neuromuscular blocking agents, nondepolarizing: Effects may be of shorter duration when administered to patients receiving carbamazepine

Oral contraceptives: Metabolism may be increased by carbamazepine, resulting in a loss of efficacy

Phenytoin: Carbamazepine levels may be decreased by phenytoin. Metabolism of phenytoin may be altered by carbamazepine; phenytoin levels may be increased or decreased.

SSRIs: Metabolism may be increased by carbamazepine (due to enzyme induction)

Theophylline: Serum levels may be reduced by carbamazepine

Thioridazine: Note: Carbamazepine suspension is incompatible with thioridazine liquid. Schedule carbamazepine suspension at least 1-2 hours apart from other liquid medicinals.

Thyroid: Serum levels may be reduced by carbamazepine

Tramadol: Tramadol's risk of seizures may be increased with TCAs (carbamazepine may be associated with similar risk due to chemical similarity to TCAs)

Tricyclic antidepressants: May increase serum concentrations of carbamazepine; carbamazepine may decrease concentrations of tricyclics due to enzyme induction

Valproic acid: Serum levels may be reduced by carbamazepine; carbamazepine levels may also be altered by valproic acid

Warfarin: Carbamazepine may inhibit the hypoprothrombinemic effects of oral anticoagulants via increased metabolism; this combination should generally be avoided

Ethanol: Avoid ethanol (may increase CNS depression).

Food: Carbamazepine serum levels may be increased if taken with food. Carbamazepine serum concentration may be increased if taken with grapefruit juice; avoid concurrent use.

Herb/Nutraceutical: Avoid evening primrose (seizure threshold decreased). Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).

Absorption: Slow

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

Protein binding: Carbamazepine: 75% to 90%, may be decreased in newborns; Epoxide metabolite: 50%

Metabolism: Hepatic via CYP3A4 to active epoxide metabolite; induces hepatic enzymes to increase metabolism

Bioavailability: 85%

Half-life elimination:

Carbamazepine: Initial: 18-55 hours; Multiple doses: Children: 8-14 hours; Adults: 12-17 hours

Epoxide metabolite: Initial: 25-43 hours

Time to peak, serum: Unpredictable:

Immediate release: Suspension: 1.5 hour; tablet: 4-5 hours

Extended release: Carbatrol®, Equetro™: 12-26 hours (single dose), 4-8 hours (multiple doses); Tegretol®-XR: 3-12 hours

Excretion: Urine 72% (1% to 3% as unchanged drug); feces (28%)

Epilepsy:

Children:

<6 years: Initial: 10-20 mg/kg/day divided twice or 3 times daily as tablets or 4 times/day as suspension; increase dose every week until optimal response and therapeutic levels are achieved

Maintenance dose: Divide into 3-4 doses daily (tablets or suspension); maximum recommended dose: 35 mg/kg/day

6-12 years: Initial: 100 mg twice daily (tablets or extended release tablets) or 50 mg of suspension 4 times/day (200 mg/day); increase by up to 100 mg/day at weekly intervals using a twice daily regimen of extended release tablets or 3-4 times daily regimen of other formulations until optimal response and therapeutic levels are achieved

Maintenance: Usual: 400-800 mg/day; maximum recommended dose: 1000 mg/day

Note: Children <12 years who receive 400 mg/day of carbamazepine may be converted to extended release capsules (Carbatrol®) using the same total daily dosage divided twice daily

Children >12 years and Adults: Initial: 200 mg twice daily (tablets, extended release tablets, or extended release capsules) or 100 mg of suspension 4 times/day (400 mg daily); increase by up to 200 mg/day at weekly intervals using a twice daily regimen of extended release tablets or capsules, or a 3-4 times/day regimen of other formulations until optimal response and therapeutic levels are achieved; usual dose: 800-1200 mg/day

Maximum recommended doses:

Children 12-15 years: 1000 mg/day

Children >15 years: 1200 mg/day

Adults: 1600 mg/day; however, some patients have required up to 1.6-2.4 g/day

Trigeminal or glossopharyngeal neuralgia: Adults: Initial: 100 mg twice daily with food, gradually increasing in increments of 100 mg twice daily as needed

Maintenance: Usual: 400-800 mg daily in 2 divided doses; maximum dose: 1200 mg/day

Elderly: 100 mg 1-2 times daily, increase in increments of 100 mg/day at weekly intervals until therapeutic level is achieved; usual dose: 400-1000 mg/day

Bipolar disorder (Equetro™): Adults: Initial: 400 mg/day in divided doses, twice daily; may adjust by 200 mg daily increments; maximum dose: 1600 mg/day

Suspension: Must be given on a 3-4 times/day schedule versus tablets which can be given 2-4 times/day. When carbamazepine suspension has been combined with chlorpromazine or thioridazine solutions a precipitate forms which may result in loss of effect. Therefore, it is recommended that the carbamazepine suspension dosage form not be administered at the same time with other liquid medicinal agents or diluents. Since a given dose of suspension will produce higher peak levels than the same dose given as the tablet form, patients given the suspension should be started on lower doses and increased slowly to avoid unwanted side effects. Should be administered with meals.

Extended release capsule (Carbatrol®, Equetro™): Consists of three different types of beads: Immediate release, extended-release, and enteric release. The bead types are combined in a ratio to allow twice daily dosing. May be opened and contents sprinkled over food such as a teaspoon of applesauce; may be administered with or without food; do not crush or chew.

Extended release tablet: Should be inspected for damage. Damaged extended release tablets (without release portal) should not be administered. Should be administered with meals; swallow whole, do not crush or chew.

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: 4-12 mcg/mL (SI: 25-51 mol/L)

Toxic concentration: >15 mcg/mL; patients who require higher levels of 8-12 mcg/mL (SI: 34-51 mol/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 mcg/mL.

Capsule, extended release (Carbatrol®, Equetro™): 100 mg, 200 mg, 300 mg

Suspension, oral: 100 mg/5 mL (10 mL, 450 mL)

Tegretol®: 100 mg/5 mL (450 mL) [citrus vanilla flavor]

Tablet (Epitol®, Tegretol®): 200 mg

Tablet, chewable (Tegretol®): 100 mg

Tablet, extended release (Tegretol®-XR): 100 mg, 200 mg, 400 mg

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