CARBAMAZEPINE = CBZ oral

Therapeutic action

• Antiseizure (antiepileptic), mood stabilizer

Indications

• Epilepsy generalised tonic-clonic seizures and focal (partial) seizures
• Neuropathic pain (alone or combined with amitriptyline)
• Prevention of recurrence of bipolar disorder 

Forms and strengths

• 200 mg tablet
• 100 mg/5 ml oral solution, to be administered using a measuring device (oral syringe, measuring spoon, or cup with graduations).

Dosage

Start with a low dose then increase gradually based on patient's response and tolerance.

Epilepsy

• Child 1 month to 11 years: start with 5 mg/kg once daily or 2.5 mg/kg 2 times daily; increase the daily dose by increments of 2.5 to 5 mg/kg every 3 to 7 days, up to 5 mg/kg 2 or 3 times daily if necessary (max. 20 mg/kg daily).

• Child 12 years and over: start with 100 to 200 mg once daily or 50 to 100 mg 2 times daily; increase the daily dose by increments of 100 to 200 mg every week, up to 200 to 400 mg 2 or 3 times daily if necessary (max. 1800 mg daily).
• Adult: start with 100 to 200 mg once daily or 50 to 100 mg 2 times daily; increase the daily dose by increments of 100 to 200 mg every week, up to 400 mg 2 or 3 times daily if necessary (max. 2 g daily). 

Neuropathic pain

• Adult: start with 200 mg once daily at bedtime for one week, then 200 mg 2 times daily for one week, then 200 mg 3 times daily

Prevention of recurrence of bipolar disorder 

• Adult: start with 100 mg 2 times daily; increase the daily dose  by increments of 200 mg every week, up to 200 mg 2 or 3 times daily if necessary (max. 1200 mg daily)

Duration

• Epilepsy, prevention of recurrence of bipolar disorder: as long as required. Do not stop treatment abruptly, even if changing to another medication.
• Neuropathic pain: continue several months after pain relief is obtained, then attempt to stop treatment.

Contra-indications, adverse effects, precautions

• Do not administer to patients with atrioventricular block, history of bone marrow depression.
• Administer with caution to patients with glaucoma, urinary retention, hepatic or renal impairment, heart failure or blood disorders and to older patients.
• May cause: 
  • headache, dizziness, confusional state and agitation in older patients; drowsiness (caution when driving or operating machinery);
  • gastrointestinal and visual disturbances, vitamin D deficiency (consider supplementation), osteoporosis, leucopenia (often transitory), rash;
  • rarely: haematologic disorders (agranulocytosis, anaemia, bone marrow depression), hypersensitivity reactions (including severe cutaneous reactions such as Stevens-Johnson, Lyell and DRESS syndromes), pancreatitis, hepatitis, cardiac conduction defect. In these cases, stop treatment. Early symptoms such as fever, rash, mouth ulcers and bleeding require immediate medical attention. 
    Hypersensitivity reactions to CBZ are more common in individuals from China and Southeast Asia.
• If possible, perform at least FBC, liver enzymes and serum sodium levels, at baseline then regularly during treatment.
• Avoid or monitor the combination with:
  • rifampicin, mefloquine (reduced effect of CBZ); 
  • erythromycin, isoniazid, fluoxetine, omeprazole, protease inhibitors, fluconazole, valproic acid, etc. (increased CBZ toxicity);
  • drugs containing alcohol, benzodiazepines, opioid analgesics, antipsychotics, first-generation antihistamines (hydroxyzine, promethazine), antidepressants, other antiseizure medications, etc. (increased sedation).
• CBZ may reduce the effect of many drugs:
  • diazepam, midazolam, oral anticoagulants, corticosteroids, tricyclic antidepressants, antipsychotics, protease inhibitors, rifampicin, itraconazole, doxycycline, tramadol, etc. Adjust dosage if necessary.
  • implants and oral contraceptives: use injectable medroxyprogesterone or an intrauterine device.
• Avoid alcohol during treatment (increased risk of adverse effects).
• Pregnancy: 
  • Epilepsy and bipolar disorder: avoid (risk of neural tube defects, cardiac and facial malformations, hypospadias).
    • In case of pregnancy during treatment of epilepsy, prefer a safer drug (levetiracetam). If CBZ is the only option, provide counselling about the risks to the child; use the lowest effective dose.
    • Administer folic acid high dose (5 mg daily) during the first trimester. Start as soon as possible, including during the preconception period in case of planned pregnancy. 
    • CBZ plasma concentrations may decrease during pregnancy. Monitor clinical response; increase dose if needed then resume the usual dose after delivery. Monitor the child for a few days (risk of withdrawal symptoms). 
  • Neuropathic pain: not recommended
• Breast-feeding: administer with caution (excreted in milk); reduce the dose if increased during pregnancy and monitor the child (risk of drowsiness, poor feeding and transient hepatic impairment). 

Remarks

• CBZ is not recommended for myoclonic, atonic and absence seizures (risk of worsening symptoms).

Storage