CARBAMAZEPINE

CARBAMAZEPINE
(kar-ba-maz'e-peen)
Apo-Carbamazepine , Carbatrol, Epitol, Equetro, Mazepine , PMS-Carbamazepine , Tegretol, Tegretol XR, Teril
Classifications: anticonvulsant, tricyclic;
Therapeutic: anticonvulsant

Pregnancy Category: D

Availability

100 mg chewable tablets; 200 mg tablets; 100 mg, 200 mg, 400 mg sustained-release tablets; 100 mg, 200 mg, 300 mg sustained-release capsules; 100 mg/5 mL suspension

Action

Structurally related to tricyclic antidepressants (TCAs) but lacks antidepressant properties. Anticonvulsant action appears to inhibit sustained repetitive impulses and reduces post-tetanic synaptic transmission in the spinal cord. It limits the spread of seizure activity. Provides relief in trigeminal neuralgia by reducing synaptic transmission within trigeminal nucleus. Also has sedative, anticholinergic, antidepressant, and muscle relaxant (by inhibition of neuromuscular transmission) effects and slight analgesic actions.

Therapeutic Effect

Effective anticonvulsant for a range of seizure disorders and as an adjuvant reduces depressive signs and symptoms and stabilizes mood. It is effective for pain and other symptoms associated with neurologic disorders.

Uses

Alone or with other anticonvulsants in treatment of grand mal and psychomotor or temporal lobe epilepsy and mixed seizures in patients who have not responded satisfactorily to other agents. Also used for symptomatic treatment of trigeminal (tic douloureux) and glossopharyngeal neuralgias and for pain and paroxysmal symptoms associated with multiple sclerosis and other neurologic disorders.

Unlabeled Uses

Certain psychiatric disorders including prophylaxis and treatment of manic-depressive illness, treatment of schizoaffective illness, resistant schizophrenia, dyscontrol syndrome; for management of alcohol withdrawal, rage outbursts, and for antidiuretic effect in diabetes insipidus.

Contraindications

Hypersensitivity to carbamazepine and to TCAs or MAOI therapy; history of myelosuppression or hematologic reaction to other drugs; increased IOP; SLE; cardiac, hepatic, or renal disease; coronary artery disease; hypertension; pregnancy (category D); children <6 y.

Cautious Use

The older adult; history of cardiac disease, alcoholism; hepatic disease; cardiac arrhythmias.

Route & Dosage

Epilepsy
Adult: PO 200 mg b.i.d., gradually increased to 800–1200 mg/d in 3–4 divided doses. Tegretol XR dosed b.i.d.
Child: PO <6 y: 10–20 mg/kg/d, may gradually increase weekly, recommended max 35 mg/kg/d in 3–4 divided doses; 6–12 y: 100 mg b.i.d., gradually increased to 400–800 mg/d in 3–4 divided doses (max: 1 g/d); <6 y: 20–30 mg/kg/d in 3–4 divided doses

Trigeminal Neuralgia
Adult: PO 100 mg b.i.d., gradually increased by 100 mg increments q12h until relief; usual dose 200–800 mg/d in 3–4 divided doses (max: 1.2 g/d). Tegretol XR dosed b.i.d.

Administration

Oral
  • Do not administer within 14 d of patient receiving a MAO inhibitor.
  • Give with a meal to increase absorption.
  • Ensure that chewable tablets are chewed or crushed before being swallowed with a liquid.
  • Ensure that sustained-release form of drug is not chewed or crushed. It must be swallowed whole.
  • Do not administer carbamazepine suspension simultaneously with other liquid medications: a precipitate may form in the stomach.

Adverse Effects (≥1%)

Body as a Whole: Myalgia, arthralgia, leg cramps, carbamazepine-induced SLE. CV: Edema, syncope, arrhythmias, heart block. GI: Nausea, vomiting, anorexia, abdominal pain, diarrhea, constipation, dry mouth and pharynx, abnormal liver function tests, hepatitis, cholestatic and hepatocellular jaundice, pancreatitis. Endocrine: Hypothyroidism, SIADH. Hematologic: Aplastic anemia, leukopenia (transient), leukocytosis, agranulocytosis, eosinophilia, thrombocytopenia. CNS: Dizziness, vertigo, drowsiness, disturbances of coordination, ataxia, confusion, headache, fatigue, listlessness, speech difficulty, development of minor motor seizures, hyperreflexia, akathisia, involuntary movements, tremors, visual hallucinations, activation of latent psychosis, aggression; agitation, respiratory depression. Skin: Skin rashes, urticaria, petechiae, erythema multiforme, Stevens-Johnson syndrome, photosensitivity reactions, altered skin pigmentation, exfoliative dermatitis, alopecia. Special Senses: Abnormal hearing acuity, scotomas, conjunctivitis, blurred vision, transient diplopia, oculomotor disturbances, oscillopsia, nystagmus. Urogenital: Urinary frequency or retention, oliguria, impotence.

Diagnostic Test Interference

False-negative pregnancy test results with tests involving human chorionic gonadotropin.

Interactions

Drug: Serum concentrations of other anticonvulsants may decrease because of increased metabolism; verapamil, erythromycin, ketoconazole, nefazodone may increase carbamazepine levels; decreases hypoprothrombinemic effects of oral anticoagulants; increases metabolism of estrogens, thus decreasing effectiveness of oral contraceptives. Food: Grapefruit juice may increase drug levels. Herbal: Ginkgo may decrease anticonvulsant effectiveness.

Pharmacokinetics

Absorption: Slowly from GI tract. Peak: 2–8 h. Distribution: Widely distributed; high concentrations in CSF; crosses placenta; distributed into breast milk. Metabolism: In liver by CYP3A4; can induce liver microsomal enzymes. Elimination: In urine and feces. Half-Life: 14–16 h (decreases with long-term use).

Nursing Implications

Assessment & Drug Effects

  • Lab tests: Baseline and periodic CBCs including platelets, reticulocytes, serum electrolytes and serum iron, liver function tests, BUN, and complete urinalysis.
  • At least 3 mo into therapy, it is recommended that physician attempt dosage reduction or termination of drug therapy, if possible, in patients with trigeminal neuralgia. Some patients develop tolerance to the effects of carbamazepine.
  • Monitor for the following reactions, which commonly occur during early therapy: drowsiness, dizziness, light-headedness, ataxia, gastric upset. If these symptoms do not subside within a few days, dosage adjustments may be indicated.
  • Withhold drug and notify physician if any of the following signs of myelosuppression occur: RBC <4 million/mm3, Hct <32%, Hgb <11 g/dL, WBC <4000/mm3, platelet count <100,000/mm3, reticulocyte count <20,000/mm3, serum iron >150 mg/dL.
  • Monitor for toxicity, which can develop when serum concentrations are even slightly above the therapeutic range.
  • Monitor I&O ratio and vital signs during period of dosage adjustment. Report oliguria, signs of fluid retention, changes in I&O ratio, and changes in BP or pulse patterns.
  • Cardiac syncope may resemble epileptic seizures. Therefore, it is recommended that patients who experience an apparent increase in frequency of seizures or a change in their character should be checked by continuous ECG monitoring for 24 h.
  • Doses higher than 600 mg/d may precipitate arrhythmias in patients with heart disease.
  • Confusion and agitation may be aggravated in the older adult; therefore, side rails and supervision of ambulation may be indicated.

Patient & Family Education

  • Discontinue drug and notify physician immediately if early signs of toxicity or a possible hematologic problem appear, (e.g., anorexia, fever, sore throat or mouth, malaise, unusual fatigue, tendency to bruise or bleed, petechiae, ecchymoses, bleeding gums, nose bleeds).
  • Avoid hazardous tasks requiring mental alertness and physical coordination until reaction to drug is known, since dizziness, drowsiness, and ataxia are common adverse effects.
  • Remain under close medical supervision throughout therapy.
  • Avoid excessive sunlight, as photosensitivity reactions have been reported. Apply a sunscreen (if allowed) with SPF of 12 or above.
  • Carbamazepine may cause breakthrough bleeding and may also affect the reliability of oral contraceptives.
  • Be aware that abrupt withdrawal of any anticonvulsant drug may precipitate seizures or even status epilepticus.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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