Carbamazepine

carbamazepine

(kar ba maz' e peen)

Apo-Carbamazepine (CAN), Carbatrol, Epitol, Equetro, Novo-Carbamaz (CAN), Tegretol, Tegretol-XR

Pregnancy Category D

Drug class

Antiepileptic

Therapeutic actions

Mechanism of action not understood; antiepileptic activity may be related to its ability to inhibit polysynaptic responses and block post-tetanic potentiation. Drug is chemically related to the TCAs.

Indications

·        Refractory seizure disorders: Partial seizures with complex symptoms (psychomotor, temporal lobe epilepsy), generalized tonic-clonic (grand mal) seizures, mixed seizure patterns or other partial or generalized seizures. Reserve for patients unresponsive to other agents with seizures difficult to control or who are experiencing marked side effects, such as excessive sedation

·        Trigeminal neuralgia (tic douloureux): Treatment of pain associated with true trigeminal neuralgia; also beneficial in glossopharyngeal neuralgia

·        Treatment of acute manic and mixed episodes associated with bipolar 1 disorder (Equetro)

·        Unlabeled uses: Neurogenic diabetes insipidus (200 mg bid–tid); certain psychiatric disorders, including schizoaffective illness, resistant schizophrenia, and dyscontrol syndrome associated with limbic system dysfunction; alcohol withdrawal (800–1,000 mg/day); restless leg syndrome (100–300 mg/day hs); non-neuritic pain syndrome (600–1,400 mg/day); hereditary or nonheriditary chorea in children (15–25 mg/kg/day).

Contraindications and cautions

·        Contraindicated with hypersensitivity to carbamazepine or TCAs, history of bone marrow depression, concomitant use of MAOIs, lactation, pregnancy.

·        Use cautiously with history of adverse hematologic reaction to any drug (increased risk of severe hematologic toxicity); glaucoma or increased IOP; history of cardiac, hepatic, or renal damage; psychiatric patients (may activate latent psychosis).

Available forms

Tablets—200 mg; chewable tablets—100 mg; ER tablets—100, 200, 400 mg; ER capsules—100, 200, 300 mg; suspension—100 mg/5 mL, 200 mg/10 mL

Dosages

Individualize dosage; a low initial dosage with gradual increase is advised.

ADULTS

·        Epilepsy: Initial dose, 200 mg PO bid on the first day; increase gradually by up to 200 mg/day in divided doses q 6–8 hr, until best response is achieved. Suspension:100 mg PO qid. Do not exceed 1,200 mg/day in patients > 15 yr; doses up to 1,600 mg/day have been used in adults (rare). For maintenance, adjust to minimum effective level, usually 800–1,200 mg/day.

·        Combination therapy: When added to existing antiepileptic therapy, do so gradually while other antiepileptics are maintained or discontinued.

·        Trigeminal neuralgia: Initial dose, 100 mg PO bid on the first day; may increase by up to 200 mg/day, using 100-mg increments q 12 hr as needed. Do not exceed 1,200 mg/day. For maintenance, control of pain can usually be maintained with 400–800 mg/day (range 200–1,200 mg/day). Attempt to reduce the dose to the minimum effective level or to discontinue the drug at least once every 3 mo.

·        Suspension: Start at 50 mg PO qid, increase by 50 mg PO qid as needed to maximum dose (Equetro).

·        Bipolar 1 disorder: 200–600 mg/day PO in divided doses; may be increased in 200-mg/day increments. Do not exceed 1,600 mg/day.

PEDIATRIC PATIENTS > 12 YR

Use adult dosage. Do not exceed 1,000 mg/day in patients 12–15 yr; 1,200 mg/day in patients > 15 yr.

PEDIATRIC PATIENTS 6–12 YR

Initial dose, 100 mg PO bid on the first day. Increase gradually by adding 100 mg/day at 6- to 8-hr intervals until best response is achieved. Do not exceed 1,000 mg/day. Dosage also may be calculated on the basis of 20–30 mg/kg/day in divided doses tid–qid.

PEDIATRIC PATIENTS < 6 YR

Optimal daily dose, < 35 mg/kg/day.

GERIATRIC PATIENTS

Use caution; drug may cause confusion, agitation.

Pharmacokinetics

Route	Onset	Peak
Oral	Slow	4–5 hr
ER oral	Slow	3–12 hr

Metabolism: Hepatic; T_1/2: 25–65 hr, then 12–17 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Feces, urine

Adverse effects

·        CNS: Dizziness, drowsiness, unsteadiness, disturbance of coordination, confusion, headache, fatigue, visual hallucinations, depression with agitation, behavioral changes in children, talkativeness, speech disturbances, abnormal involuntary movements, paralysis and other symptoms of cerebral arterial insufficiency, peripheral neuritis and paresthesias, tinnitus, hyperacusis, blurred vision, transient diplopia and oculomotor disturbances, nystagmus, scattered punctate cortical lens opacities, conjunctivitis, ophthalmoplegia, fever, chills; SIADH

·        CV: CHF, aggravation of hypertension, hypotension, syncope and collapse, edema, primary thrombophlebitis, recurrence of thrombophlebitis, aggravation of CAD, arrhythmias and AV block; CV complications

·        Dermatologic: Pruritic and erythematous rashes, urticaria, Stevens-Johnson syndrome, photosensitivity reactions, alterations in pigmentation, exfoliative dermatitis, alopecia, diaphoresis, erythema multiforme and nodosum, purpura, aggravation of lupus erythematosus

·        GI: Nausea, vomiting, gastric distress, abdominal pain, diarrhea, constipation, anorexia, dryness of mouth or pharynx, glossitis, stomatitis; abnormal LFTs, cholestatic and hepatocellular jaundice, hepatitis, massive hepatic cellular necrosis with total loss of intact liver tissue

·        GU: Urinary frequency, acute urinary retention, oliguria with hypertension, renal failure, azotemia, impotence, proteinuria, glycosuria, elevated BUN, microscopic deposits in urine

·        Hematologic: Hematologic disorders (severe bone marrow depression)

·        Respiratory: Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis or pneumonia

Interactions

Drug-drug

·        Increased serum levels and manifestations of toxicity with erythromycin, troleandomycin, cimetidine, danazol, isoniazid, propoxyphene, verapamil; dosage of carbamazepine may need to be reduced (reductions of about 50% recommended with erythromycin)

·        Increased CNS toxicity with lithium

·        Increased risk of hepatotoxicity with isoniazid (MAOI qualities); because of the chemical similarity of carbamazepine to the TCAs and because of the serious adverse interaction of TCAs and MAOIs, discontinue MAOIs for minimum of 14 days before carbamazepine administration

·        Decreased absorption with charcoal

·        Decreased serum levels and decreased effects of carbamazepine with barbiturates

·        Increased metabolism but no loss of seizure control with phenytoin, primidone

·        Increased metabolism of phenytoin, valproic acid

·        Decreased anticoagulant effect of warfarin, oral anticoagulants; dosage of warfarin may need to be increased during concomitant therapy but decreased if carbamazepine is withdrawn

·        Decreased effects of nondepolarizing muscle relaxants, haloperidol

·        Decreased antimicrobial effects of doxycycline

Nursing considerations

Assessment

·        History: Hypersensitivity to carbamazepine or TCAs; history of bone marrow depression; concomitant use of MAOIs; history of adverse hematologic reaction to any drug; glaucoma or increased IOP; history of cardiac, hepatic, or renal damage; psychiatric history; lactation; pregnancy

·        Physical: Weight; T; skin color, lesions; palpation of lymph glands; orientation, affect, reflexes; ophthalmologic examination (including tonometry, funduscopy, slit lamp examination); P, BP, perfusion; auscultation; peripheral vascular examination; R, adventitious sounds; bowel sounds, normal output; oral mucous membranes; normal urinary output, voiding pattern; CBC including platelet, reticulocyte counts and serum iron; LFTs, urinalysis, BUN, thyroid function tests, EEG

Interventions

·        Use only for classifications listed. Do not use as a general analgesic. Use only for epileptic seizures that are refractory to other safer agents.

·        Give drug with food to prevent GI upset.

·        Do not mix suspension with other medications or elements—precipitation may occur.

·        WARNING: Reduce dosage, discontinue, or substitute other antiepileptic medication gradually. Abrupt discontinuation of all antiepileptic medication may precipitate status epilepticus.

·        Suspension will produce higher peak levels than tablets—start with a lower dose given more frequently.

·        Ensure that patient swallows ER tablets whole—do not cut, crush, or chew.

·        Arrange for frequent LFTs; discontinue drug immediately if hepatic dysfunction occurs.

·        WARNING: Arrange for patient to have CBC, including platelet, reticulocyte counts, and serum iron determination, before initiating therapy; repeat weekly for the first 3 mo of therapy and monthly thereafter for at least 2–3 yr. Discontinue drug if there is evidence of marrow suppression, as follows:

Erythrocytes	< 4 million/mm3
Hct	< 32%
Hgb	< 11 gm/dL
Leukocytes	< 4,000/mm3
Platelets	< 100,000/mm3
Reticulocytes	< 0.3% (20,000/mm2)
Serum iron	150 g/100 mL

·        Arrange for frequent eye examinations, urinalysis, and BUN determinations.

·        Arrange for frequent monitoring of serum levels of carbamazepine and other antiepileptics given concomitantly, especially during the first few weeks of therapy. Adjust dosage on basis of data and clinical response.

·        Counsel women who wish to become pregnant; advise the use of barrier contraceptives.

·        Evaluate for therapeutic serum levels (usually 4–12 mcg/mL).

Teaching points

·        Take drug with food as prescribed. Swallow extended-release tablets whole, do not cut, crush, or chew them. If using Equetro capsules, they may be opened and contents sprinkled over soft food, such as 1 teaspoon of applesauce.

·        Do not discontinue this drug abruptly or change dosage, except on the advice of your physician.

·        Avoid alcohol, sleep-inducing, or over-the-counter drugs; these could cause dangerous effects.

·        Arrange for frequent checkups, including blood tests, to monitor your response to this drug. Keep all appointments for checkups.

·        Use contraceptives at all times; if you wish to become pregnant, you should consult your physician.

·        Wear a medical alert tag at all times so that any emergency medical personnel will know that you have epilepsy and are taking antiepileptic medication.

·        You may experience these side effects: Drowsiness, dizziness, blurred vision (avoid driving or performing other tasks requiring alertness or visual acuity); GI upset (take the drug with food or milk; eat frequent small meals).

·        Report bruising, unusual bleeding, abdominal pain, yellowing of the skin or eyes, pale feces, darkened urine, impotence, central nervous system disturbances, edema, fever, chills, sore throat, mouth ulcers, rash, pregnancy.

Adverse effects in Italic are most common; those in Bold are life-threatening.