Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI8OJL6UB)
  Drug Name Carbamazepine Drug Info Eslicarbazepine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anticonvulsants/Antimanic Agents Anticonvulsants
  Structure

 Mechanism of Carbamazepine-Eslicarbazepine Interaction (Severity Level: Moderate)
     UGT induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Carbamazepine Eslicarbazepine
      Mechanism UGT inducer UGT substrate
      Key Mechanism Factor 1
Factor Name UDP-glucuronosyltransferase Structure Sequence
Protein Family UDP-glycosyltransferase family
Protein Function
[Isoform 1]: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558).
    Click to Show/Hide
      Mechanism Description
  • Increased metabolism of Eslicarbazepine caused by Carbamazepine mediated induction of UGT

Recommended Action
      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.

References
1 Bialer M, Soares-da-Silva P "Pharmacokinetics and drug interactions of eslicarbazepine acetate." Epilepsia 53 (2012): 935-46. [PMID: 22612290]
2 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3 Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc, Marlborough, MA.