Drug Interaction Report

MONITOR: Coadministration with a carbonic anhydrase inhibitor may increase the serum concentration and the risk of toxicity of carbamazepine. The mechanism of this interaction has not been delineated. In one report, three pediatric patients receiving the highest tolerable dose of carbamazepine without adverse effects experienced a 25% to 50% increase in their serum carbamazepine levels following the addition of acetazolamide 250 mg to 750 mg daily. In another report involving 54 pediatric patients with epilepsy, seizure control improved following the addition of acetazolamide 10 mg/kg daily and serum carbamazepine levels increased by 1 to 6 mg/L in 60% of 33 patients sampled. In those patients who developed carbamazepine toxicity, symptoms developed within 1 to 10 days of starting acetazolamide.

MANAGEMENT: Clinical monitoring of carbamazepine serum concentrations is recommended and the dosage should be adjusted accordingly. Patients should be advised to report possible signs of carbamazepine toxicity, such as headache, nausea, dizziness, slurred speech, nystagmus, visual disturbances, tremors, and ataxia, to their caregiver.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.