Oxcarbazepine

Actions

• Blocks voltage-dependent Na+ channels at high firing frequencies.
• Exerts effect on K+ channels.

Metabolism

Hepatic

Enzymes involved

• CYP3A4
• CYP2C19

Elimination

Renal >94%

Enzyme induction

• CYP3A4
• CYP3A5

Enzyme inhibition

• CYP2C19

Therapeutic serum concentration range

5-50 μg/ml

Half-life

5-11 hours

Plasma protein binding

40%

Important side-effects

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

Approximately 25-30% of patients who have had hypersensitivity reactions to carbamazepine will experience hypersensitivity reactions with oxcarbazepine.

Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Patients carrying the HLA-B*1502 allele may be at increased risk for SJS/TEN with oxcarbazepine treatment. Testing for the presence of the HLA-B*1502 allele should be considered in patients with Chinese ancestry prior to initiating treatment with oxcarbazepine.

Indications

Focal seizures with or without generalization.

May aggravate myoclonic and absence seizures.

Dosing recommendation

Start with 300 mg/day.

Increase to target dose over 1–3 weeks.

Target dose: 600–2400 mg/day divided in 2-3 doses.

Renal impairment

In patients with creatinine clearance <30 ml/min the initial dose should be reduced by 50%. Serum concentration should be monitored closely.

Hepatic impairment

Dose adjustment is not necessary in patients with mildly to moderately impaired hepatic function. Insufficient data exist about oxcarbazepine in patients with severely impaired hepatic function.

Serum concentration changes during pregnancy

Total level decreases by 30-50%. Free fraction decreases by 30-50%.