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Carbamazepine

Pronunciation

Pronunciation: KAR-ba-MAZ-e-peen
Class: Anticonvulsant

Trade Names

Carbatrol
- Capsules, extended-release 100 mg
- Capsules, extended-release 200 mg
- Capsules, extended-release 300 mg

Epitol
- Tablets 200 mg

Equetro
- Capsules, extended-release 100 mg
- Capsules, extended-release 200 mg
- Capsules, extended-release 300 mg

Tegretol
- Tablets, chewable 100 mg
- Tablets 200 mg
- Suspension 100 mg per 5 mL

Tegretol XR
- Tablets, extended-release 100 mg
- Tablets, extended-release 200 mg
- Tablets, extended-release 400 mg

Apo-Carbamazepine (Canada)
Gen-Carbamazepine CR (Canada)
PMS-Carbamazepine (Canada)
Sandoz Carbamazepine (Canada)
Taro-Carbamazepine (Canada)

Pharmacology

Appears to provide anticonvulsant effects by reducing polysynaptic responses and blocking posttetanic potentiation. Mechanism of action for other effects is unknown.

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Pharmacokinetics

Absorption

Therapeutic levels are 4 to 12 mcg/mL.

Suspension

T max is approximately 1.5 h.

Tablets

T max is 4 to 5 h.

Extended-release

T max is 3 to 12 h ( Tegretol XR ).

Distribution

76% protein bound. Rapidly crosses the placenta.

Metabolism

Induces its own metabolism; metabolized in the liver by CYP3A4 to the active metabolite carbamazepine-10,11-epoxide (shown to be equipotent to carbamazepine).

Elimination

Initial t ½ is 25 to 65 h, decreasing to 12 to 17 h on repeated doses. 72% is excreted in the urine (3% as unchanged drug) and 28% in the feces.

Special Populations

Children

More rapidly metabolized to 10,11-epoxide.

Indications and Usage

Treatment of epilepsy (eg, partial seizures with complex symptoms, generalized tonic-clonic seizures, mixed seizure patterns, other partial or generalized seizures); treatment of pain associated with trigeminal neuralgia.

Equetro only

Treatment of acute manic and mixed episodes associated with bipolar 1 disorder.

Unlabeled Uses

Treatment of restless leg syndrome; alternative/adjunctive treatment for certain symptoms associated with borderline personality disorder; alternative to benzodiazepines for managing alcohol withdrawal; adjunctive therapy for schizophrenia; treatment of postherpetic neuralgia.

Contraindications

Hypersensitivity to tricyclic antidepressants or carbamazepine; history of bone marrow depression; concomitant use of MAOIs. Discontinue MAOIs at least 14 days before administration of carbamazepine.

Dosage and Administration

Epilepsy
Adults and Children older than 12 yr of age Initial dosage

PO 200 mg twice daily (tablets) or 100 mg (1 tsp) 4 times daily (suspension). Increase weekly by up to 200 mg/day in 2 divided doses for extended-release or 3 to 4 divided doses for other formulations to reach minimum effective dose (max, 1,000 mg/day in children 12 to 15 yr of age; 1,200 mg/day in children older than 15 yr of age; 1,600 mg/day in adults).

Maintenance

800 to 1,200 mg/day.

Adults and Children older than 12 yr of age (extended-release) Initial dosage

PO 200 mg twice daily.

Children 6 to 12 yr of age Initial dosage

PO 100 mg twice daily (tablets) or 50 mg 4 times daily (suspension). Increase weekly by 100 mg/day in 3 to 4 divided doses (extended-release formulations use a twice-daily regimen) to reach minimum effective dose (max, 1,000 mg/day).

Maintenance

400 to 800 mg/day in 3 to 4 divided doses.

Children younger than 6 yr of age Initial dosage

PO 10 to 20 mg/kg/day in 2 or 3 divided doses (tablet) or 10 to 20 mg/kg/day in 4 divided doses (suspension). Increase weekly to achieve optimal clinical response when administered in 3 or 4 divided daily doses (max, 35 mg/kg/day).

Maintenance

Less than 35 mg/kg/day.

Trigeminal Neuralgia
Adults Initial dosage

PO 100 mg twice daily (tablets) or 50 mg 4 times daily (suspension). May increase by up to 200 mg/day (tablets, 100 mg increments every 12 h; suspension, 50 mg 4 times daily) as needed (max, 1,200 mg/day).

Maintenance

Usually 400 to 800 mg/day. Attempt to reduce the dosage or discontinue the drug once every 3 mo.

Adults (extended-release) Initial dosage

PO 100 mg twice daily (tablets) or 200 mg once daily (capsules) (max, 1,200 mg/day).

Bipolar Disorder ( Equetro only)
Adults Initial dosage

PO 200 mg twice daily. Increase in 200 mg/day increments to optimal clinical response (max, 1,600 mg/day).

General Advice

May be used alone or in combination with other antiepileptic drugs (AEDs) for treatment of seizures or with analgesics for treatment of trigeminal neuralgia.

  • Extended-release capsules
  • Administer without regard to meals. Administer with food if GI upset occurs.
  • Advise patient to swallow whole and to not crush or chew the capsule.
  • Inform patient that capsules may be opened and beads sprinkled over food (eg, tsp of applesauce or similar food product) and immediately swallowed without chewing. Caution patient not to chew the beads.
  • Extended-release tablets
  • When converting from tablets to extended-release tablets, administer same number of mg per day divided into 2 daily doses.
  • Inspect tablet for chips or cracks. Do not administer damaged tablets.
  • Administer prescribed dose with food. Advise patient to swallow tablet whole and to not crush or chew the tablet.
  • Suspension
  • When converting from tablets to suspension, start the suspension at a lower dose and increase the dose slowly to minimize adverse reactions.
  • Shake suspension well before measuring dose. Measure dose using dosing cup, spoon, or syringe.
  • Do not administer carbamazepine suspension simultaneously with other liquid medications or diluents.
  • Ensure that lower initial doses and slower dose escalation are used when treating with suspension because a given dose of suspension will produce higher blood levels than the same dose given as a tablet.
  • Administer prescribed dose with food.
  • Tablets
  • Administer prescribed dose with food.

Storage/Stability

Store all doseforms at controlled room temperature (59° to 86°F). Protect from light and moisture. Protect suspension from freezing.

Drug Interactions

Acetaminophen, aripiprazole, benzodiazepines (eg, midazolam), bupropion, citalopram, clozapine, corticosteroids (eg, dexamethasone), cyclosporine, dicumarol, itraconazole, lapatinib, levothyroxine, methadone, olanzapine, oxcarbazine, praziquantel, risperidone, sertraline, simvastatin, succinimides (eg, ethosuximide), tiagabine, topiramate, tramadol, ziprasidone, zonisamide

Levels may be reduced by carbamazepine.

Acetazolamide, azole antifungal agents, danazol, diltiazem, grapefruit juice, loratadine, macrolide antibiotics (except azithromycin), niacinamide, nicotinamide, propoxyphene, quinine, terfenadine, verapamil

May increase carbamazepine levels and result in toxicity.

Alcohol

Increased risk of CNS adverse reactions.

Anticoagulants

May decrease anticoagulant effects.

Barbiturates

May result in decreased carbamazepine serum concentrations, possibly leading to decreased effectiveness.

Charcoal, activated

May reduce absorption of carbamazepine.

Cimetidine

May result in carbamazepine toxicity.

Cisplatin, doxorubicin, methsuximide, rifamycins (eg, rifampin)

May increase carbamazepine metabolism, reducing plasma levels and the therapeutic effect.

Clomipramine

Levels may be increased by carbamazepine.

Contraceptives, hormonal

Causes breakthrough bleeding and reduces effectiveness of contraceptives.

Delavirdine

Coadministration may lead to loss of virologic response and possible resistance. May decrease delavirdine levels and increase carbamazepine levels.

Doxycycline hyclate

May decrease doxycycline hyclate levels.

Felbamate

May decrease concentrations of felbamate or carbamazepine.

Felodipine

May decrease effects of felodipine.

Haloperidol

May decrease effects of haloperidol.

Hydantoins (eg, phenytoin)

May decrease carbamazepine levels; may alter hydantoin levels.

Isoniazid

May result in toxicity of isoniazid, carbamazepine, or both.

Lamotrigine

Lamotrigine levels may be decreased, while levels of the active metabolite of carbamazepine may be increased.

Liquid medicinals or diluents

May result in the formation of an insoluble precipitate in the GI tract.

Lithium

May cause adverse CNS effects regardless of drug levels.

MAOIs, voriconazole

Coadministration with carbamazepine is contraindicated.

Nefazodone

Coadministration is contraindicated. Elevated carbamazepine levels and lower nefazodone levels may result.

Nondepolarizing muscle relaxants

May make these agents less effective.

Primidone

Decreased carbamazepine levels. Primidone's active metabolite (phenobarbital) may be increased.

Protease inhibitors (eg, indinavir)

Carbamazepine levels may be elevated and protease inhibitor levels may be decreased, resulting in antiretroviral treatment failure.

Quetiapine

Quetiapine levels may be reduced; concentrations of the active carbamazepine metabolite may be increased.

SSRIs (eg, fluoxetine, fluvoxamine)

Increased carbamazepine levels with possible toxicity.

Theophylline

May reduce effects of theophylline and carbamazepine. Theophylline levels may be increased or decreased.

Tricyclic antidepressants

May increase carbamazepine levels; may decrease tricyclic antidepressant levels.

Valproic acid

May decrease valproic acid levels; may alter carbamazepine levels.

Laboratory Test Interactions

Thyroid function tests showed decreased values. Interference with some pregnancy tests has been reported.

Adverse Reactions

Cardiovascular

Aggravation of coronary artery disease, aggravation of hypertension, arrhythmias, AV block, CHF, fainting, hypotension, syncope, thrombophlebitis.

CNS

Dizziness (44%); somnolence (32%); headache (22%); ataxia (15%); amnesia, asthenia (8%); anxiety, depression, manic depressive reaction (7%); speech disorder (6%); ataxia (5%); depersonalization, extrapyramidal syndrome, insomnia, nervousness, suicide attempts (less than 5%); aseptic meningitis with myoclonus, cerebral artery insufficiency, confusion, depression with agitation, disturbances in coordination, drowsiness, fatigue, hyperacusis, involuntary movements, neuroleptic malignant syndrome, paralysis, paresthesias, peripheral neuritis, talkativeness, visual hallucinations.

Dermatologic

Rash (13%); pruritus (8%); alopecia, photosensitivity (less than 5%); aggravation of disseminated systemic lupus erythematosus, altered skin pigmentation, diaphoresis, erythema multiforme and nodosum, erythematous rash, exfoliative dermatitis, hirsutism, pruritic rash, purpura, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), urticaria.

EENT

Amblyopia (6%); diplopia, ear pain, pharyngitis, rhinitis (less than 5%); blurred vision, conjunctivitis, dry pharynx, nystagmus, oculomotor disturbances, scattered punctuate cortical lens opacities, tinnitus.

GI

Nausea (29%); vomiting (18%); diarrhea, dyspepsia (10%); dry mouth (8%); constipation (5%); abdominal pain, anorexia, gastric distress, glossitis, pancreatitis, stomatitis.

Genitourinary

UTI (less than 5%); acute urinary retention, albuminuria, azotemia, elevated BUN, glucosuria, impotence, microscopic urine deposits, oliguria with elevated blood pressure, renal failure, urinary frequency.

Hematologic-Lymphatic

Leukopenia, lymphadenopathy (less than 5%); acute intermittent porphyria, adenopathy, agranulocytosis, aplastic anemia, bone marrow suppression, eosinophilia, leukocytosis, pancytopenia, thrombocytopenia.

Hepatic

Abnormal LFTs (less than 5%); cholestatic jaundice, hepatic failure, hepatitis, hepatocellular jaundice.

Metabolic-Nutritional

Decreased plasma calcium; elevated cholesterol, HDL cholesterol, and triglycerides; hyponatremia; SIADH; water intoxication.

Musculoskeletal

Back pain (5%); aching joints and muscles, leg cramps.

Respiratory

Bronchitis, sinusitis (less than 5%); dyspnea, pneumonia, pneumonitis, pulmonary hypersensitivity.

Miscellaneous

Infection, pain (12%); accidental injury (7%); chest pain (5%); edema, peripheral edema (less than 5%); chills, fever, lupus erythematosus–like syndrome, multi-organ hypersensitivity.

Precautions

Warnings

Aplastic anemia and agranulocytosis

Has been reported with use. The risk is 5 to 8 times greater than in the general population.

Obtain complete pretreatment hematological testing as a baseline. If, in the course of treatment, a patient exhibits low or decreased WBC or platelet count, monitor the patient closely.

Serious dermatologic reactions and HLA-B*1502 allele

Serious and sometimes fatal dermatologic reactions, including Stevens-Johnson syndrome and TEN, have been reported in 1 to 6 per 10,000 carbamazepine users. Studies in patients of Chinese ancestry found a strong association between the risk of developing Stevens-Johnson syndrome or TEN and the inherited genetic allelic variant HLA-B*1502. Screen patients who are genetically at risk and, if positive for the allele, when possible, do not prescribe carbamazepine.


Monitor

Monitor carbamazepine serum levels as indicated to evaluate therapeutic response, compliance, and possible toxicity. Assess CBC and renal and hepatic function prior to initiating therapy. Monitor renal and hepatic function periodically during treatment. Monitor CBC closely if, in the course of treatment, low or decreased WBC or platelet count is noted. Obtain baseline and periodic eye examinations, including slit-lamp, funduscopy, and tonometry. Obtain high-resolution HLA-B*1502 typing for patients who are genetically at risk.


Pregnancy

Category D .

Lactation

Excreted in breast milk.

Children

Management of epilepsy in children is derived from clinical investigations in adults. Safety and efficacy of Equetro are not established.

Elderly

No data are available.

Special Risk Patients

Use with caution in patients with prior adverse hematologic reactions to any drug; cardiac, renal, or hepatic disease; interrupted courses of therapy with carbamazepine; and mixed seizure disorders that include atypical absence seizures.

Hazardous Tasks

May cause dizziness or drowsiness.

Anticholinergic activity

Carbamazepine has mild anticholinergic activity; closely observe patients with increased IOP during therapy.

Dermatologic reactions

Rarely, severe dermatologic reactions, including TEN and Stevens-Johnson syndrome, have been reported.

Discontinuation of treatment

Abrupt discontinuation in patients with seizure disorder may precipitate status epilepticus. If treatment is to be discontinued, gradually taper the dose and monitor patient for seizure activity.

Suicide

Possibility of suicide attempts is inherent in bipolar disorder. Closely supervise high-risk patients.

Latent psychosis

Because of the relationship of carbamazepine to other tricyclic compounds, latent psychosis can possibly be activated.

Overdosage

Symptoms

Abnormal EEG, acetonuria, anuria, ataxia, coma, conduction disorders, convulsions, dizziness, drowsiness, dysmetria, glucosuria, hyperreflexia followed by hyporeflexia, hypertension, hypotension, impairment of consciousness, irregular breathing, leukocytosis, motor restlessness, muscle twitching, mydriasis, nausea, nystagmus, oliguria, psychomotor disturbances, respiratory depression, shock, tachycardia, tremor, urinary retention, vomiting.

Patient Information

  • Advise patient to read the patient information leaflet before starting therapy and with each refill.
  • Instruct patient with seizures or bipolar disorder to continue to take other medications for those conditions as prescribed by health care provider.
  • Advise patient to take each dose with food (except extended-release capsules).
  • Advise patient that medication is started at a low dose and is then gradually increased as tolerated until max benefit has been obtained.
  • Caution patient to avoid grapefruit products while taking carbamazepine because of risk of toxicity.
  • Advise patient to take a missed dose as soon as remembered, but if several hours have passed or it is nearing the time for the next scheduled dose, to skip the missed dose and take the next dose at the regularly scheduled time. Caution patient to never double the dose to catch up.
  • Advise patient that if medication needs to be discontinued, it will be slowly withdrawn over a period of several weeks unless safety concerns (eg, rash) require a more rapid withdrawal.
  • Caution patient being treated for trigeminal neuralgia that carbamazepine is not a simple analgesic (pain reliever), and not to use for treatment of trivial aches or pains.
  • Advise patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Instruct patient or caregiver to immediately notify health care provider if any of the following occur: appetite loss, confusion, fever, persistent nausea or headache, rash, small purple spots under the skin, sore throat, swollen glands, ulcers in mouth, unusual bleeding or bruising, or yellowing of eyes or skin.
  • Instruct patient to contact health care provider if coordination problems, difficulty with concentration, excessive drowsiness or fatigue, or speech or language problems develop.
  • Instruct patient with seizures to inform health care provider if seizures get worse or if new types of seizures develop.
  • Caution patient that drug may cause drowsiness and dizziness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patient to avoid unnecessary exposure to sunlight or tanning lamps and to use sunscreen and wear protective clothing to avoid photosensitivity reactions.
  • Advise women using combination oral contraceptive to use additional nonhormonal form of contraception because carbamazepine may cause a reduction in effectiveness of combination oral contraceptives.
  • Extended-release capsules
  • Advise patient to take prescribed dose without regard to meals, but to take with food if stomach upset occurs. Caution patient to swallow capsule whole and not to crush or chew the capsule.
  • Advise patient that capsules may be opened, the beads sprinkled over food (eg, tsp of applesauce or similar food product), and the drug/food mixture swallowed immediately, without chewing, and followed by a glass of water. Caution patient not to prepare the mixture ahead of time and store.
  • Extended-release tablets
  • Instruct patient using extended-release tablet to inspect each tablet for chips or cracks in the outer coating and not to take a damaged tablet.
  • Advise patient that the extended-release coating is not absorbed and may be seen in the stool. Advise patient not to be concerned because this is normal and does not reduce the effectiveness of the medication because the medication inside the tablet has already been released and absorbed into the body.
  • Suspension
  • Advise patient or caregiver to shake suspension well before measuring dose, and to measure and administer prescribed dose using dosing cup, dosing spoon, or dosing syringe.
  • Caution patient or caregiver not to administer carbamazepine suspension simultaneously with other liquid medications or mix with other diluents.

Copyright © 2009 Wolters Kluwer Health.

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