Details of Drug-Drug Interaction
| Drug General Information (ID: DDIXLJ8P0A) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Drug Name | Estrone | Drug Info | Paritaprevir | Drug Info | |||||
| Drug Type | Small molecule | Small molecule | |||||||
| Therapeutic Class | Antimenopausal Agents | Antiviral Agents | |||||||
| Structure | |||||||||
| Mechanism of Estrone-Paritaprevir Interaction (Severity Level: Major) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| UGT inhibition Click to Show/Hide Mechanism Graph | |||||||||
 |
|||||||||
| Drug Name | Estrone | Paritaprevir | |||||||
| Mechanism | UGT substrate | UGT inhibitor | |||||||
| 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 |
|
||||||||
| Recommended Action | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Management | Caution is recommended if estrogen-containing products are used in patients receiving ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. Liver function tests should be performed on all patients during the first 4 weeks of treatment and as clinically indicated thereafter. If ALT is elevated above baseline at any time during treatment, the test should be repeated and monitored closely. Therapy should be discontinued if ALT levels remain persistently greater than 10 times the ULN, or if ALT elevations are accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. | ||||||||