Drug Interaction Report

GENERALLY AVOID: Coadministration with carbamazepine may significantly decrease the plasma concentrations and pharmacologic effects of calcium channel blockers (CCBs), especially the dihydropyridines (e.g., amlodipine, felodipine, nicardipine, nifedipine, nimodipine, nisoldipine). The proposed mechanism is carbamazepine induction of CYP450-mediated metabolism. In one study, the relative bioavailability of felodipine in 10 subjects receiving enzyme-inducing anticonvulsants (including four on carbamazepine alone and three on carbamazepine with phenytoin) was found to be just 6.6% that of control subjects, which represented less than 1% systemic availability of the oral dose. Likewise, in eight patients with epilepsy receiving long-term enzyme-inducing anticonvulsant therapy (including four on carbamazepine with either phenytoin, phenobarbital, or clobazam), systemic exposure (AUC) to a single 60 mg dose of nimodipine was reported to be approximately 7-fold lower than in control subjects. A case report describes loss of blood pressure control in association with undetectable nilvadipine plasma concentrations 3 days after increasing carbamazepine dosage to 600 mg/day. Nilvadipine levels increased after carbamazepine was discontinued and the patient's blood pressure returned to normal after about 2 weeks.

MANAGEMENT: Concomitant use of calcium channel blockers with potent CYP450 3A4 inducers such as carbamazepine should generally be avoided. If coadministration is necessary, pharmacologic response should be monitored more closely following the initiation, discontinuation or change of dosage of carbamazepine, and the CCB dosage adjusted accordingly.

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.