Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIANLJ92F)
  Drug Name Diethylstilbestrol Drug Info Valproic acid Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antineoplastics Anticonvulsants
  Structure

 Mechanism of Diethylstilbestrol-Valproic acid Interaction (Severity Level: Moderate)
     UGT induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Diethylstilbestrol Valproic acid
      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 Valproic acid caused by Diethylstilbestrol mediated induction of UGT

Recommended Action
      Management Pharmacologic response and serum valproic levels should be monitored more closely whenever estrogen- and/or progestin-containing drugs are added to or withdrawn from therapy, and the valproic acid dosage adjusted as necessary. Patients should be advised to contact their physician if they experience loss of seizure control or symptoms of valproic acid toxicity such as tremors, ataxia, nystagmus, increased seizures, and changes in mental status. In patients receiving oral contraceptives, gradual transient increases in valproic acid levels will likely occur during the pill-free week for women not also taking an enzyme-inducing drug (e.g., carbamazepine, phenytoin, phenobarbital, primidone, rifampin). The increase in valproic acid levels will be greater if the dose of valproic acid is increased in the few days before or during the pill-free week.

References
1 Product Information. Depakote (divalproex sodium). Abbott Pharmaceutical, Abbott Park, IL.
2 Product Information. Depacon (valproic acid). Abbott Pharmaceutical, Abbott Park, IL.
3 Herzog AG, Farina EL, Blum AS "Serum valproate levels with oral contraceptive use." Epilepsia 46 (2005): 970-1.
4 Reimers A, Brodtkorb E, Sabers A. "Interactions between hormonal contraception and antiepileptic drugs: Clinical and mechanistic considerations." Seizure. 2015;28:66-70.