Anticonvulsant (Carbamazepine) dose and use in pregnancy

Usual Adult Dose for Epilepsy

Initial dose: 200 mg orally twice a day (immediate and extended release) or 100 mg orally 4 times a day (suspension).
Increase dose at weekly intervals in 200 mg/day increments using a twice daily regimen of extended release or a three times a day or four times a day regimen of the other formulations.
Maintenance dose: 800 to 1200 mg/day.
Dosage generally should not exceed 1200 mg/day.
However, doses up to 1600 mg/day have been used in rare instances.

Usual Adult Dose for Trigeminal Neuralgia

Initial dose: 100 mg orally twice a day (immediate or extended release) or 50 mg orally 4 times a day (suspension).
May increase by up to 200 mg/day using increments of 100 mg every 12 hours (immediate or extended release), or 50 mg four times a day. (suspension), only as needed to achieve freedom from pain. Do not exceed 1200 mg/ day.
Maintenance dose: 400 to 800 mg/day.
Some patients may be maintained on as little as 200 mg/day while others may require as much as 1200 mg/day. At least once every 3 months throughout the treatment period, attempts should be made to reduce the dose to the minimum effective level or to discontinue the drug.

Usual Adult Dose for Bipolar Disorder

Initial dose: 200 mg orally in tablet or capsule form every 12 hours or 100 mg of oral solution 4 times a day.

Tablets and solution:
Following autoinduction, higher doses will be necessary to maintain drug levels within the therapeutic range of 6 to 12 mcg/mL. The daily dose should be increased in 100 to 200 mg increments at 1 to 2 week intervals.

Maintenance dose: up to 1200 mg daily in 3 or 4 divided doses may be necessary to maintain plasma levels in the therapeutic range.

Extended release capsules:
The dose should be adjusted in 200 mg daily increments (increase by 100 mg twice daily) to achieve optimal clinical response. Doses higher than 1600 mg per day have not been studied.

Usual Adult Dose for Diabetic Neuropathy

Initial dose: 100 mg orally in tablet form every 12 hours or 50 mg of oral solution 4 times a day.

The daily dose should be increased in 100 mg increments at 1 to 2 week intervals.

Maintenance dose: 600 to 1200 mg daily in 3 or 4 divided doses may be necessary to maintain plasma levels in the therapeutic range.

Usual Pediatric Dose for Epilepsy

<6 years:
Initial dose: 10 to 20 mg/kg/day orally in 2 to 3 divided doses (tablets) or 4 divided doses (suspension) .
Increase dose at weekly intervals to achieve optimal clinical response.
Maximum dose: 35 mg/kg/day.
If satisfactory response not achieved, measure levels to determine if in therapeutic range.

6 to 12 years:
Initial dose: 100 mg orally twice a day (immediate or extended release tablets) or 50 mg orally 4 times a day (suspension).
Increase dose at weekly intervals in 100 mg/day increments using a twice daily regimen of extended release or a three times a day or four times a day regimen of the other formulations.
Maintenance dose: 400 to 800 mg/day.
Maximum dose: 1000 mg/day.

>12 years:
Initial dose: 200 mg orally twice a day (immediate and extended release) or 100 mg orally 4 times a day (suspension).
Increase dose at weekly intervals in 200 mg/day increments using a twice a day regimen of extended release or a three times daily to four times daily regimen of the other formulations.
Maintenance dose: 800 to 1200 mg/day.
Dosage generally should not exceed 1000 mg in children 12 to 15 years and 1200 mg/day in patients >15 years.
Doses up to 1600 mg/day have been used in rare instances.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Dosage should be adjusted to the needs of the individual patient. A low initial daily dosage with a gradual increase is advised. As soon as adequate control is achieved, the dosage may be reduced very gradually to the minimum effective level.

Precautions

When added to existing anticonvulsant therapy, carbamazepine should be added gradually while the other anticonvulsants are maintained or gradually decreased, except phenytoin, which may have to be increased.

Dialysis

Carbamazepine is slightly dialyzed by hemodialysis. The dialysis clearance averages 54 mL/min. Using a Cobe Century II hollow tube dialyzer with a cuprophane membrane, 10% of a dose is removed during 4 hour of hemodialysis.

Hemoperfusion has been reported to be useful in the removal of carbamazepine during acute overdose.

Other Comments

Damaged tablets or extended-release tablets without a release portal should not be consumed.

Tablets (including the chewable and extended release forms) and the suspension should be taken with meals. The extended release capsules can be taken with or without food.

If necessary, carbamazepine capsules can be opened and the contents sprinkled over food, such as a teaspoonful of applesauce or other similar food products. Carbamazepine capsules or their contents should not be crushed or chewed.

Carbamazepine Pregnancy Warnings

A prospective controlled study of 210 women treated with carbamazepine at least during the first trimester has suggested a twofold increase in the rate of major congenital anomalies. The results were 12/160 in the carbamazepine group versus 18/560 in the general control. There was also a birth weight reduction of approximately 250 g after in utero exposure to carbamazepine. A prospective case control cohort study of pregnant women with epilepsy has reported an association between carbamazepine therapy and fetal death and anomalies. In that study, carbamazepine was associated with the lowest risk of three major antiepileptic drugs (phenytoin, phenobarbital, and carbamazepine). The relative risk of abnormal outcome was 0.019 in carbamazepine-treated women. In one study of 100 pregnancies in which the mothers were taking carbamazepine, 7 malformed offspring were reported. No significant differences in carbamazepine and metabolite levels were observed between those pregnancies which ended in malformation and those pregnancies which ended in normal offspring. Many of the epileptic women in this study were taking other antiseizure medications. Another study has suggested that carbamazepine exerts no negative effects on neurodevelopment in children exposed to carbamazepine in utero. In one case of massive overdose of carbamazepine during the third or fourth week post-conception, the fetus developed a large neural tube defect. A case of transient cholestatic hepatitis has been reported in an infant between the third and seventh weeks of life. The author of the report stated that it was "most likely due to carbamazepine exposure during pregnancy and breast feeding." To provide information regarding the effects of in utero exposure to carbamazepine, physicians are advised to recommend that pregnant patients taking carbamazepine enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.
Carbamazepine has been assigned to pregnancy category D by the FDA. Carbamazepine can cause fetal harm when administered to a pregnant woman. Epidemiological data suggest that there may be an association between the use of carbamazepine during pregnancy and congenital malformations, including spina bifida. The prescribing physician should weigh the benefits of therapy against the risks in treating or counseling women of childbearing potential. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Tests to detect defects using current accepted procedures should be considered a part of routine prenatal care in childbearing women receiving carbamazepine. Patients should be encouraged to enroll in the NAAED Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888233-2334.

Carbamazepine Breastfeeding Warnings

Carbamazepine and its epoxide metabolite are transferred to breast milk during lactation. Because of the potential for serious adverse reactions in nursing infants from carbamazepine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
A case of transient cholestatic hepatitis has been reported in an infant between the third and seventh weeks of life. The author of the report stated that it was "most likely due to carbamazepine exposure during pregnancy and breast feeding."