Carbamazepine

Actions

• Blocks voltage-dependent Na+ channels at high firing frequencies.
• Acts as GABA receptor agonist.
• Potentiates GABA receptors.

Metabolism

Hepatic

Enzymes involved

• CYP3A4
• CYP2C19

Elimination

Renal 72%

Enzyme induction

• CYP1A2
• CYP2B6
• CYP2C8
• CYP2C9
• CYP2C19
• CYP3A4

Therapeutic serum concentration range

4-12 μg/ml

Half-life

16-24 hours

Plasma protein binding

75-85%

Important side-effects

Serious dermatologic reactions including Stevens-Johnson syndrome and TEN. The risk is particularly high (10-70 times higher) in patients of Chinese ancestry that are carriers of the HLA-B*1502 allele. Screening patients of Chinese ancestry for HLA-B*1502 carrier status is advised before treatment with Carbamazepine is initiated. Moderate risk of dermatologic reactions exists in patients of European, Japanese or Korean ancestry that are carriers of the HLA-A*3101 allele.

Aplastic Anemia and Agranulocytosis.

Suicidal behavior and ideation.

SIADH resulting in hyponatremia. Risk is higher in patients treated with diuretics or other drugs associated with inappropriate ADH secretion, elderly and patients with renal disease associated with low sodium levels.

Hepatitis.

Indications

Primarily effective against focal seizures, with or without secondary generalisation.

Can also be effective against primarily generalized tonic-clonic seizures.

May aggravate myoclonic and absence seizures.

Dosing recommendation

Start with 100 or 200 mg/day.

Increase to target dose over 1–4 weeks.

Target dose: 400–1600 mg/day divided in 2-3 doses (2 doses with sustained release formulations).

Renal impairment

Monitor serum concentration in patients with impaired renal function. A dose reduction to 75% might be necessary in severe renal failure and dialysis patients.

Hepatic impairment

Monitor serum concentration in patients with impaired hepatic function.

Serum concentration changes during pregnancy

Total level decreases by 0-12%.