carbamazepine

Absorption: Absorption is slow but complete. Suspension produces earlier, higher peak, and lower trough levels.

Distribution: Widely distributed to tissues. Crosses the blood-brain barrier.

Protein Binding: 75–90%.

Metabolism/Excretion: Extensively metabolized in the liver by the CYP3A4 isoenzyme to active epoxide metabolite; epoxide metabolite has anticonvulsant and antineuralgic activity.

Half-Life: Children: 8–14 hr; Adults: 12–17 hr.

Time/Action Profile ⬆ ⬇

(anticonvulsant activity)

ROUTE	ONSET	PEAK	DURATION
PO	up to 1 mo‡	4–5 hr‡	6–12 hr
PO-ER	up to 1 mo‡	2–3–12 hr‡	12 hr

‡Onset of antineuralgic activity is 8–72 hr.

‡Listed for tablets; peak level occurs 1.5 hr after a chronic dose of suspension.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to carbamazepine or tricyclic antidepressants;
Bone marrow suppression;
Concomitant use or use within 14 days of MAO inhibitors;
Concurrent use of nefazodone or NNRTIs that are CYP3A4 substrates;
Lactation: Lactation.

Use Cautiously in:

All patients (may ↑ risk of suicidal thoughts/behaviors);
Cardiac or hepatic disease;
Renal failure (dosing adjustment required for CCr <10 mL/min);
↑intraocular pressure;
OB: Use during pregnancy only if potential maternal benefits outweigh potential fetal risks; additional vitamin K during last wk of pregnancy has been recommended;
Geri: Appears on Beers list. May worsen or cause syndrome of inappropriate antidiuretic hormone (SIADH) secretion in older adults. Use with caution in older adults and closely monitor sodium concentrations when starting therapy or dose.

Patients positive for HLA-B*1502 or HLA-A*3101 alleles (unless benefits clearly outweigh the risks) (↑ risk of serious skin reactions).

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, heart block, HF, hypertension, hypotension, syncope

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), nail shedding, photosensitivity, rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), urticaria

EENT: blurred vision, corneal opacities, nystagmus

Endo: SIADH

F and E: hyponatremia

GI: ↑liver enzymes, HEPATOTOXICITY, PANCREATITIS

GU: hesitancy, urinary retention

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, eosinophilia, leukopenia, lymphadenopathy, THROMBOCYTOPENIA

Metab: weight gain

Neuro: ataxia, drowsiness, fatigue, psychosis, sedation, SUICIDAL THOUGHTS, vertigo

Resp: pneumonitis

Misc: chills, fever

Interactions ⬆ ⬇

Drug-drug:

May significantly ↓ levels of nefazodone or NNRTIs that are CYP3A4 substrates; concurrent use contraindicated.
Concurrent or recent (within 2 wk) use of MAO inhibitors may result in hyperpyrexia, hypertension, seizures, and death; use contraindicated.
May ↓ levels and effectiveness of acetaminophen, alprazolam, aprepitant, buprenorphine, bupropion, calcium channel blockers, citalopram, clonazepam, corticosteroids, cyclosporine, doxycycline, estrogen-containing contraceptives, everolimus, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, methadone, midazolam, olanzapine, paliperidone, phenytoin, protease inhibitors, risperidone, sertraline, sirolimus, tacrolimus, tadalafil, theophylline, tiagabine, topiramate, tramadol, trazodone, tricyclic antidepressants, valproic acid, warfarin, ziprasidone, and zonisamide.
May ↓ aripiprazole levels; double the aripiprazole dose.
May ↓ levels and effectiveness of temsirolimus and lapatinib; avoid concurrent use.
May ↓ levels and effectiveness of apixaban, dabigatran, edoxaban, and rivaroxaban; avoid concurrent use.
Aprepitant, brivaracetam, cimetidine, ciprofloxacin, clarithromycin, danazol, dantrolene, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, ibuprofen, isoniazid, itraconazole, ketoconazole, loratadine, olanzapine, omeprazole, oxybutynin, protease inhibitors, trazodone, voriconazole, and verapamil may ↑ levels and risk of toxicity.
Rifampin, phenobarbital, and phenytoin may ↓ levels and effectiveness.
May ↑ risk of hepatotoxicity from isoniazid.
May ↑ risk of CNS toxicity from lithium.
May ↓ levels and effects of nondepolarizing neuromuscular blocking agents.
May ↑ risk of toxicity from cyclophosphamide.

Grapefruit juice↑ levels and the risk of toxicity.

Route/Dosage ⬆ ⬇

When converting from immediate-release (IR) to extended-release (ER) formulation, administer same total daily dose (in 2 divided doses).

Seizures

PO (Adults and Children >12 yr): 200 mg twice daily (IR tablets and ER tablets/capsules) or 100 mg 4 times daily (suspension); ↑ by up to 200 mg/day in divided doses (every 12 hr for ER tablets; every 6–8 hr for IR tablets and suspension) every 7 days until therapeutic levels are achieved (usual range = 600–1200 mg/day); not to exceed 1000 mg/day in children 12–15 yr old or 1200 mg/day in children 15–18 yr old or 1600 mg/day in adults.
PO (Children 6–12 yr): 100 mg twice daily (IR tablets or ER tablets/capsules) or 50 mg 4 times daily (suspension). ↑ by up to 100 mg/day in divided doses (every 12 hr for ER tablets; every 6–8 hr for IR tablets and suspension) every 7 days until therapeutic levels are achieved (usual range = 400–800 mg/day); not to exceed 1000 mg/day.
PO (Children <6 yr): 10–20 mg/kg/day in 2–3 divided doses (IR tablets) or in 4 divided doses (suspension); may ↑ at weekly intervals until optimal response and therapeutic levels are achieved; not to exceed 35 mg/kg/day.

Trigeminal Neuralgia

PO (Adults ): 100 mg twice daily (IR or ER tablets), 200 mg once daily (ER capsules), or 50 mg 4 times daily (suspension); ↑ by up to 200 mg/day in divided doses (every 12 hr for IR tablets or ER tablets/capsules; every 6 hr for suspension) as needed until pain is relieved (usual range = 400–800 mg/day); not to exceed 1200 mg/day.

Acute Manic or Mixed Episodes Associated with Bipolar I Disorder

PO (Adults ): Equetro: 200 mg twice daily; ↑ by 200 mg/day until optimal response is achieved; not to exceed 1600 mg/day.

Availability ⬆ ⬇

(Generic available)

Immediate-release tablets: 200 mg
Chewable tablets: 100 mg; 200 mg
Extended-release capsules (Carbatrol, Equetro): 100 mg; 200 mg; 300 mg
Extended-release tablets (Tegretol XR): 100 mg; 200 mg; 400 mg
Oral suspensioncitrus-vanilla flavor: 100 mg/5 mL

Assessment ⬆ ⬇

Monitor closely for changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Monitor for changes in skin condition in early therapy. SJS and TEN are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502 (occurs almost exclusively in patients with Asian ancestry, including South Asian Indians). Screen patients of Asian ancestry for the HLA-B*1502 allele before starting treatment with carbamazepine. If positive, carbamazepine should not be started unless the expected benefit outweighs increased risk of serious skin reactions. Patients who have been taking carbamazepine for more than a few mo without developing skin reactions are at low risk of these events ever developing.
Monitor for signs and symptoms of DRESS syndrome (fever, rash, and/or lymphadenopathy with organ system involvement [hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis]) resembling an acute viral infection with eosinophilia. Discontinue carbamazepine if other cause not determined.
Seizures: Assess frequency, location, duration, and characteristics of seizure activity.
Trigeminal Neuralgia: Assess for facial pain (location, intensity, duration). Ask patient to identify stimuli that may precipitate facial pain (hot or cold foods, bedclothes, touching face).
Bipolar Disorder: Assess mental status (mood, orientation, behavior) and cognitive abilities before and periodically during therapy.

Lab Test Considerations:

Monitor CBC, including platelet count, reticulocyte count, and serum iron, at baseline, weekly during the first 2 mo, and yearly thereafter for evidence of potentially fatal blood cell abnormalities. Discontinue therapy if bone marrow depression occurs.
- Perform genetic testing for the HLA-B*1502 allele in patients of Asian ancestry prior to beginning therapy.
- Perform liver function tests, urinalysis, electrolytes, serum creatinine, and BUN at baseline and routinely performed. May cause ↑ AST, ALT, serum alkaline phosphatase, bilirubin, BUN, urine protein, and urine glucose levels.
- Monitor ECG and serum electrolytes before and periodically during therapy. May cause hyponatremia.
- May occasionally cause ↑ serum cholesterol, high-density lipoprotein, and triglyceride concentrations.
- May cause false-negative pregnancy test results with tests that determine human chorionic gonadotropin.

Toxicity and Overdose:

Serum blood levels should be routinely monitored during therapy. Therapeutic levels range from 4 to 12 mcg/mL.

Implementation ⬆ ⬇

Do not confuse carbamazepine with oxcarbazepine. Do not confuse Tegretol with Tegretol XR.
Implement seizure precautions as indicated.
PO: Administer medication with food to minimize gastric irritation. May take at bedtime to reduce daytime sedation. DNC: Do not crush or chew extended-release tablets. Extended-release capsules may be opened and the contents sprinkled on applesauce or other similar foods.
- Do not administer suspension simultaneously with other liquid medications or diluents; mixture produces an orange rubbery mass.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take carbamazepine around the clock, as directed. Take missed doses as soon as possible but not just before next dose; do not double doses. Notify health care professional if more than one dose is missed. Discontinue gradually to prevent seizures. Instruct patient to read the Medication Guide before starting and with each Rx refill in case of changes.
- Advise patient to avoid grapefruit and grapefruit juice during therapy.
- May cause dizziness or drowsiness. Advise patients to avoid driving or other activities requiring alertness until response to medication is known.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Instruct patient to report behavioral changes, skin rash, fever, sore throat, mouth ulcers, easy bruising, petechiae, unusual bleeding, abdominal pain, chills, rash, pale stools, dark urine, or jaundice to health care professional immediately. Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide, new or worse depression, new or worse anxiety, feeling very agitated or restless, panic attacks, trouble sleeping, new or worse irritability, acting aggressive, being angry or violent, acting on dangerous impulses, an extreme increase in activity and talking, or other unusual changes in behavior or mood occur.
- Inform patient that coating of Tegretol XR is not absorbed but is excreted in feces and may be visible in stool.
- Advise patient not to take alcohol or other CNS depressants concurrently with this medication.
- Caution patients to use sunscreen and protective clothing to prevent photosensitivity reactions.
- Inform patient that frequent mouth rinses, good oral hygiene, and sugarless gum or candy may help reduce dry mouth. Saliva substitute may be used. Consult dentist if dry mouth persists >2 wk.
- Instruct patient to notify health care professional of medication regimen before treatment or surgery.
- May cause fetal harm. Advise females of reproductive potential to use a nonhormonal form of contraception while taking carbamazepine, to avoid breastfeeding during therapy, and to notify health care professional if pregnancy is planned or suspected or if breastfeeding. May reduce effects of estrogen-containing contraceptives. Encourage patients who become pregnant to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334 or on the web at www.aedpregnancyregistry.org. Enrollment must be done by patients themselves.
- Emphasize the importance of follow-up lab tests and eye exams to monitor for side effects.
Seizures: Advise patients to carry identification describing disease and medication regimen at all times.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇