Drug interactions between Lamictal and Tegretol

ADJUST DOSE: Coadministration with carbamazepine may decrease the serum concentrations of lamotrigine. The mechanism is carbamazepine induction of the hepatic glucuronidation of lamotrigine. Studies have found that carbamazepine can reduce lamotrigine serum concentrations by approximately 40%, and there have been case reports of patients who developed significantly increased lamotrigine levels and/or lamotrigine toxicity following withdrawal of carbamazepine.

MONITOR: Lamotrigine has been reported to enhance the toxicity of carbamazepine by increasing the plasma concentrations of the pharmacologically active epoxide metabolite of carbamazepine, although data are conflicting. In one report, mean serum carbamazepine-10,11-epoxide concentration increased by 45% and the carbamazepine-10,11-epoxide to carbamazepine ratio increased by 19% in nine patients following the introduction of lamotrigine. Four of the patients also experienced symptoms of clinical toxicity during the combination. Other investigators have failed to find evidence of a pharmacokinetic interaction in either children or adults. However, toxicity has occurred in the absence of significant alterations in carbamazepine or carbamazepine-10,11-epoxide pharmacokinetics, suggesting the possibility of a pharmacodynamic interaction. One study found that toxicity is more likely to occur if the initial carbamazepine level is high (above 8 mg/L in study patients) upon lamotrigine introduction.

MANAGEMENT: When lamotrigine is added to existing therapy containing carbamazepine without valproate, the initial dosage of lamotrigine should be 0.6 mg/kg/day in two divided doses (2 to 12 years of age) or 50 mg/day (older than 12 years of age) for the first 2 weeks. The initial dosage should be doubled for the next 2 weeks, then increased by 1.2 mg/kg/day or 100 mg/day every 1 to 2 weeks as needed and as tolerated. The usual maintenance dosage is 5 to 15 mg/kg/day (up to 400 mg/day) in children up to 12 years of age and 300 to 500 mg/day (400 mg/day for the treatment of bipolar disorder) in older patients. Patients should be advised to promptly notify their physician if they experience worsening of seizure control, increased adverse effects, or signs of carbamazepine toxicity such as dizziness, drowsiness, vertigo, diplopia, nystagmus, ataxia, and nausea. A reduction in carbamazepine dosage generally will resolve the toxicity without the need to discontinue either drug. However, a reevaluation of all antiepileptic agents in the regimen should be considered prior to making any changes. If carbamazepine is discontinued, lamotrigine half-life will be prolonged and a dosage adjustment may be necessary. Prescribers should refer to the lamotrigine product labeling for complete dosing information.