Carbamazepine


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Epilepsy Initial: 100-200 mg once daily or bid, may increase gradually. Maintenance: 0.8-1.2 g/day in divided doses. Max: 2 g/day. Trigeminal neuralgia Initial: 100-200 mg bid, may increase gradually. Maintenance: 400-800 mg/day in divided doses. Max: 1.2 g/day. Prophylaxis of bipolar disorder Initial: 400 mg/day in divided doses, may increase gradually. Maintenance: 400-600 mg/day in divided doses. Max: 1.6 g/day. Rectal Epilepsy Max: 250 mg 6 hrly for not more than 7 days.
Dosage Details
Oral
Epilepsy
Adult: Initially, 100-200 mg once daily or bid, gradually increased by increments of up to 200 mg daily every wk. Maintenance: 0.8-1.2 g daily in divided doses. Max: 2 g daily.
Child: 10-20 mg/kg daily in divided doses. Alternatively, <1 yr 100-200 mg daily. Max: 35 mg/kg daily; 1-5 yr 200-400 mg daily. Max: 35 mg/kg daily; >5-10 yr 400-600 mg daily. Max: 1 g daily; >10-15 yr 0.6-1 g daily. Max: 1 g daily.

Oral
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.

Oral
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.

Rectal
Epilepsy
Adult: Max: 250 mg 6 hrly for not more than 7 days in patients incapable of oral treatment. When changing from oral to rectal route, increase dose by approx 25%.
Child: Same as adult dose.
Special Patient Group
Pharmacogenomics:

Human Leukocyte Antigen (HLA) alleles has a significant role in predisposing patients to immune-mediated adverse reactions. HLA-B*1502 and HLA-A*3101 may be risk factors for the development of serious cutaneous adverse drug reactions.

HLA-B*1502: May increase risk of severe skin reactions, particularly Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Those of Asian descent have a higher likelihood of carrying this variant. It is found almost exclusively in individuals with ancestry across broad area of Asia. Greater than 15 % is reported to be positive in Hong Kong, Thailand, Malaysia, and parts of the Philippines, about 10 % in Taiwan, and 4 % in North China. South Asians, including Indians, averaging 2-4 %. HLA-B*1502 is present in less than 1 % of the population in Japan and Korea. It is largely absent in individuals not of Asian origin (e.g. Caucasians, African-Americans, Hispanics, and Native Americans).

Prior to treatment initiation, screen for presence of HLA-B*1502 in genetically at-risk population. If test is positive (carrier of 1 or 2 allele), carbamazepine should not be used unless the benefits clearly outweigh the risks. Genetic testing is not recommended in patients who have previously taken carbamazepine for less than 3 months without any adverse effects.

HLA-A*3101: May increase risk of skin reactions, particularly mild reactions and multi-organ hypersensitivity syndrome. Those at-risk includes the European (2-5 %) and Japanese (9 %) ancestry. Consider screening for presence of HLA-A*3101. If tested positive, avoid use.
Administration
Should be taken with food. Avoid grapefruit juice.
Contraindications
Patients w/ AV block, history of bone marrow depression or history of hepatic porphyrias. Concurrent use w/ or w/in 14 days of MAOI use. Concurrent use w/ nefazodone.
Special Precautions
Patient w/ history of cardiac disease and haematological reactions to other drugs. HLA-B*1502 or HLA-A*3101 positive patients. Not effective in absence, myoclonic, or akinetic seizures. Avoid abrupt withdrawal. Hepatic and renal impairment. Pregnancy and lactation.
Adverse Reactions
Dizziness, drowsiness, ataxia; nausea, vomiting, dry mouth, abdominal pain, anorexia. Diarrhoea or constipation; mild skin reactions, disturbances of cerebellar and oculo-motor function, transient leucopenia, eosinophilia, leucocytosis, thrombocytopaenia, purpura; lyphadenopathy, splenomegaly, pneumonitis, abonormalities of liver and kidney function, hepatitis, cholestatic jaundice; hyponatraemia, oedema; paraesthesia, headache, arrhythmias and heart block, impotence, male infertility, gynaecomastia, galactorrhoea, dystonias and dykinesias w/ asterixis; local irritation w/ rectal use.
Potentially Fatal: HLA-B*1502 and HLA-A*3101 allele: Serious dermatologic reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis). Apalastic anaemia, agranulocytosis, CV effects (e.g. CHF).
Patient Counseling Information
This drug may cause dizziness, drowsiness, ataxia, diplopia, impaired accommodation and blurred vision, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor CBC w/ platelet count and differential, electrolytes, serum carbamazepine levels, thyroid function, suicidal ideation and behaviours.
Overdosage
Symptoms:  Dizziness, ataxia, drowsiness, stupor, nausea, vomiting, opisthotonos, restlessness, agitation, disorientation, tremor, involuntary movements, adiadochokinesis, abnormal reflexes (hypoactive or hyperactive), mydriasis, nystagmus, flushing, cyanosis, urinary retention. Hypotension or HTN may develop. Coma may follow. Management: Induce emesis or employ gastric lavage. General supportive treatment.
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.
Food Interaction
Additive sedative effect w/ alcohol. Increased plasma concentrations w/ grapefruit juice. Decreased plasma concentrations w/ St John's wort.
Lab Interference
False positive perphenazine concentrations in HPLC analysis. False positive TCA concentration in fluorescence polarised immunoassay method. May interact w/ some pregnancy tests.
Action
Description: Carbamazepine depresses activity in the nucleus ventralis of the thalamus, reduces synaptic propagation of excitatory impulses or decreases summation of temporal stimulation leading to neural discharge by limiting influx of Na ions across cell membrane or other unknown mechanisms. It stimulates the release of antidiuretic hormone (ADH) and potentiates its action in promoting reabsorption of water.
Pharmacokinetics:
Absorption: Slowly and irregularly absorbed from the GI tract. Bioavailability: 85-100%.
Distribution: Widely distributed throughout the body. Detected in CSF (approx 15-22% of serum concentrations), brain, duodenal fluids, bile and saliva. Crosses the placenta and enters breast milk. Plasma protein binding: Approx 70-80%.
Metabolism: Undergoes extensive hepatic metabolism by CYP3A4 and CYP2C8 isoenzymes.
Excretion: Via urine (as metabolites) and faeces (small amounts). Mean plasma half-life: 12-24 hr (repeated dosage).
Chemical Structure

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Storage
Store below 30°C.
MIMS Class
ATC Classification
N03AF01 - carbamazepine ; Belongs to the class of carboxamide derivatives antiepileptic.
Disclaimer: This information is independently developed by MIMS based on Carbamazepine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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