Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIOWHBDNP)
  Drug Name Phenobarbital Drug Info Eslicarbazepine Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Anticonvulsants Anticonvulsants
  Structure

 Mechanism of Phenobarbital-Eslicarbazepine Interaction (Severity Level: Moderate)
     UGT induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Phenobarbital 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 Phenobarbital mediated induction of UGT

Recommended Action
      Management The potential for diminished therapeutic effects of eslicarbazepine should be considered when prescribed in combination with phenobarbital or primidone, a drug that is partially metabolized to phenobarbital. A dosage increase for eslicarbazepine acetate may be required based on efficacy and tolerability.

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