Drug Interaction Report

ADJUST DOSE: Coadministration with carbamazepine may increase the risk of some adverse effects associated with eslicarbazepine such as dizziness, diplopia, and abnormal coordination. In controlled trials, dizziness was reported in 30% versus 11.5%, diplopia in 11.4% versus 2.4%, and abnormal coordination in 6.7% versus 2.7% of subjects receiving eslicarbazepine acetate with carbamazepine and without carbamazepine, respectively. The potential for increased risk of other specific adverse reactions should be considered. Pharmacokinetically, carbamazepine may reduce the plasma concentrations of eslicarbazepine. In healthy study subjects, eslicarbazepine systemic exposure (AUC) decreased by an average of 32% when eslicarbazepine acetate 800 mg once daily was coadministered with carbamazepine 400 mg twice daily. The proposed mechanism is carbamazepine induction of the glucuronidation of eslicarbazepine. No changes were observed in the AUC of carbamazepine or its metabolite, carbamazepine-epoxide.

MANAGEMENT: When eslicarbazepine acetate is coadministered with carbamazepine, dosage modifications for one or both drugs may be required based on efficacy and tolerability. Patients should be closely monitored for dose-related adverse reactions such as dizziness, ataxia, vertigo, gait disturbance, nystagmus, and abnormal coordination, particularly during the titration period and in patients 60 years of age and older.

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.

The recommended maximum number of medicines in the 'dibenzazepine anticonvulsant agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'dibenzazepine anticonvulsant agents' category:

• eslicarbazepine
• Tegretol (carbamazepine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.