Carbamazepine Dosing Schedule and Half-Life
Half-Life
Carbamazepine has a variable half-life that decreases significantly with chronic use due to autoinduction: initially 25-65 hours after first dose, decreasing to 12-17 hours after 3-5 weeks of continuous therapy. 1
- In children on long-term therapy, the half-life ranges from 6-12 hours, which is shorter than the 15-hour half-life seen in adults 2
- After single oral doses, the elimination half-life is approximately 35 hours (range 18-65 hours), but this decreases to 10-20 hours during multiple dosing due to autoinduction of oxidative metabolism 3
- Autoinduction is completed after 3-5 weeks of fixed dosing 1
Dosing Schedule
Adults and Children Over 12 Years
For epilepsy, start with 200 mg twice daily (400 mg/day total), increasing by up to 200 mg/day at weekly intervals using a 3-4 times daily regimen until optimal response is achieved. 1
- Maximum dose should not exceed 1,000 mg daily in children 12-15 years of age, and 1,200 mg daily in patients above 15 years 1
- Doses up to 1,600 mg daily have been used in adults in rare instances 1
- Maintenance dosage is typically 800-1,200 mg daily 1
- Because of carbamazepine's relatively short half-life (12-17 hours with chronic use), the total dosage should be administered in at least two divided doses to avoid excessively high peak blood levels 4
Children 6-12 Years
Start with 100 mg twice daily (200 mg/day total), increasing by up to 100 mg/day at weekly intervals using a 3-4 times daily regimen. 1
- Maximum dose generally should not exceed 1,000 mg daily 1
- Maintenance dosage is typically 400-800 mg daily 1
Children Under 6 Years
Start with 10-20 mg/kg/day divided into 2-3 doses, increasing weekly to achieve optimal clinical response administered 3-4 times daily. 1
- Maintenance dosage should ordinarily not exceed 35 mg/kg/day 1
- No recommendation regarding safety at doses above 35 mg/kg/24 hours can be made 1
Trigeminal Neuralgia
Start with 100 mg twice daily (200 mg/day total), increasing by up to 200 mg/day using increments of 100 mg every 12 hours as needed to achieve freedom from pain. 1
- Do not exceed 1,200 mg daily 1
- Maintenance dose is typically 400-800 mg daily, though some patients may be maintained on as little as 200 mg daily 1
- The American Academy of Neurology recommends starting at 200 mg at night with gradual increase of 200 mg every 7 days to a final dose of 400-1,200 mg/day divided into 2-3 doses 5
Therapeutic Monitoring
Therapeutic blood levels should be maintained between 4-8 mcg/mL, with usual adult therapeutic levels between 4-12 mcg/mL. 6, 1
- The best anticonvulsant effect appears to be obtained at plasma levels of approximately 5-10 mcg/mL (20-40 micromol/L) 3
- Plasma levels of carbamazepine are variable and may range from 0.5 to 25 mcg/mL, with no apparent relationship to daily intake 1
- Once seizures are controlled, plasma levels should be measured to establish optimum levels for individual patients 4
Important Administration Details
Medication should be taken with meals. 1
- A low initial daily dosage with gradual increase is advised 1
- As soon as adequate control is achieved, dosage may be reduced very gradually to the minimum effective level 1
- Therapy should begin gradually, with initial doses increased slowly over 1-2 weeks as tolerated to minimize side effects 4
Common Pitfalls
A single daily dose is insufficient; at minimum 2 doses per day are appropriate in most cases, but some patients may benefit from more frequent dosing (3-4 times daily) to avoid side effects related to peak levels. 3