Carbamazepine
Indications
Carbamazepine is used for:
Epilepsy, Schizophrenia, Bipolar disorder, Trigeminal neuralgia
Adult Dose
Oral
Epilepsy
Adults - Initial: Either 200 mg b.i.d. for tablets and XR tablets, or 1 teaspoon q.i.d. for suspension (400 mg/day).
Increase at weekly intervals by adding up to 200 mg/day using a b.i.d or a t.i.d. or q.i.d. regimen of the either formulations until the optimal response is obtained.
Doses up to 1600 mg daily have been used in adults in rare instances.
Maintenance: usually 800-1200 mg daily.
Trigeminal neuralgia
Adult: Initially, 100-200 mg bid, increased gradually as needed. Maintenance: 400-800 mg daily in divided doses. Max: 1.2 g daily.
Prophylaxis of bipolar disorder
Adult: Initially, 400 mg daily in divided doses, increased gradually as necessary. Maintenance: 400-600 mg daily in divided doses. Max: 1.6 g daily.
Child Dose
Epilepsy
<6 Years
Initial (oral suspension): 10-20 mg/kg/day PO q6hr
Initial (tablet): 10-20 mg/kg/day PO q8-12hr
Maintenance: For tablets or suspension may divide frequency into 3-4 times daily not to exceed 35 mg/kg/day
6-12 Years
Initial (oral suspension): 50 mg PO q6hr
Initial (tablet, immediate- or extended-release): 100 mg PO q12hr; may increase qWeek by 100 mg/day
Maintenance: 400-800 mg/day PO q6-8hr (immediate-release); q12hr (extended-release)
Not to exceed 1000 mg/day
>12 Years
Initial (oral suspension): 10 mL (200 mg) PO q6hr
Initial (tablet, immediate- or extended-release): 200 mg PO q12hr
May increase by up to 200 mg/day qWeek; q12hr (extended-release tablet); q6-8hr (other formulations)
12-15 years: Dose not to exceed 1000 mg/day
>15 years: Dose not to exceed 1200 mg/day
Renal Dose
Administration
Should be taken with food. Avoid grapefruit juice.
Contra Indications
Hypersensitivity; bone marrow depression; porphyria, pregnancy.
Precautions
Lactation; CV disease, hepatic or renal disorders, history of blood disorders or haematological reactions to other drugs; glaucoma; skin disorders; elderly, patients on MAO inhibitors; abrupt withdrawal of treatment.
Lactation: Enters breast milk; not recommended (AAP states compatible with nursing; however, adverse reactions in breastfeeding infant are possible; take into account the importance of the drug to the mother before deciding to discontinue breastfeeding or the drug)
Pregnancy-Lactation
Pregnancy category: D
Lactation: Enters breast milk; not recommended (AAP states compatible with nursing; however, adverse reactions in breastfeeding infant are possible; take into account the importance of the drug to the mother before deciding to discontinue breastfeeding or the drug)
Interactions
Increased plasma levels w/ CYP3A4 inhibitors (e.g. cimetidine). Decreased plasma levels w/ CYP3A4 inducers (e.g. cisplatin). Increased risk of neurotoxic side effects w/ lithium. May decrease the effect of hormonal contraceptives. Increased plasma levels of active metabolite carbamazepine-10, 11-epoxide w/ loxapine, quetiapine, primidone, progabide, valproic acid and valpromide. May increase cyclophosphamide levels. May reduce exposure of aripiprazole. May reduce plasma levels of tacrolimus, temsirolimus and lapatinib. May increase risk of isoniazid-induced hepatotoxicity. Risk of symptomatic hyponatraemia w/ diuretics (e.g. hydrochlorothiazide, furosemide).
Potentially Fatal: May decrease serum concentrations of nefazodone and its active metabolites. Toxic reactions may develop when taken concurrently w/ MAOIs.
Adverse Effects
Side effects of Carbamazepine :
>10%
Ataxia (15%), Dizziness (44%), Drowsiness (32%), Nausea (29%), Vomiting (18%)
1-10%
Dry mouth (8%)
Rare
MI, Stevens-Johnson syndrome
Hepatic failure, Punctate cortical lens opacities, Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Frequency Not Defined
Hemopoietic system: Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, leukopenia, leukocytosis, eosinophilia, anemia, acute intermittent porphyria, variegate porphyria, porphyria cutanea tarda
Skin: Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) (see Black Box Warnings), pruritic and erythematous rashes, urticaria, photosensitivity reactions, alterations in skin pigmentation, exfoliative dermatitis, erythema multiforme and nodosum, purpura, aggravation of disseminated lupus erythematosus, alopecia, diaphoresis, and onychomadesis
Cardiovascular system: Congestive heart failure, edema, aggravation of hypertension, hypotension, syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block, thrombophlebitis, thromboembolism, and adenopathy or lymphadenopathy
Liver: Abnormalities in liver function tests, cholestatic and hepatocellular jaundice, hepatitis; very rare cases of hepatic failure
Pancreatic: Pancreatitis
Respiratory System: Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis, or pneumonia
Genitourinary System: Urinary frequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, renal failure, and impotence (rare reports of impaired male fertility and/or abnormal spermatogenesis)
Laboratory: Albuminuria, glycosuria, elevated BUN, decreased plasma calcium, and microscopic deposits in the urine
Nervous system: Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances, nystagmus, speech disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with agitation, talkativeness, tinnitus, hyperacusis, neuroleptic malignant syndrome; isolated cases of neuroleptic malignant syndrome
Digestive system: Nausea, vomiting, gastric distress and abdominal pain, diarrhea, constipation, anorexia, and dryness of the mouth and pharynx, including glossitis, and stomatitis
Eyes: Scattered punctate cortical lens opacities, increased intraocular pressure as well as conjunctivitis
Musculoskeletal system: Aching joints and muscles, and leg cramps
Metabolism: Fever and chills; SIADH; cases of frank water intoxication, with decreased serum sodium (hyponatremia) and confusion; decreased levels of plasma calcium leading to osteoporosis
Potentially Fatal: Agranulocytosis, aplastic anaemia, hepatic failure, severe exfoliative dermatitis and Stevens-Johnson syndrome.
Mechanism of Action
Carbamazepine reduces polysynaptic responses and blocks post-tetanic potentiation. It is effective in partial and generalised convulsions as well as in mixed types but not in petit mal seizures. It reduces or abolishes pain in trigeminal and glossopharyngeal neuralgia.