Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI3JFSMYB)
Drug Name			Ospemifene		Drug Info		Eltrombopag		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Selective Estrogen Receptor Modulators				Platelet-Stimulating Agents
Structure

Mechanism of Ospemifene-Eltrombopag Interaction (Severity Level: Moderate)
UGT inhibition Click to Show/Hide Mechanism Graph

Drug Name		Ospemifene				Eltrombopag
Mechanism		UGT1A3 inhibitor				UGT1A3 substrate
Key Mechanism Factor 1
		Factor Name		UDP-glucuronosyltransferase 1A3				× Structure Sequence MATGLQVPLPWLATGLLLLLSVQPWAESGKVLVVPIDGSHWLSMREVLRELHARGHQAVVLTPEVNMHIKEENFFTLTTYAISWTQDEFDRHVLGHTQLYFETEHFLKKFFRSMAMLNNMSLVYHRSCVELLHNEALIRHLNATSFDVVLTDPVNLCAAVLAKYLSIPTVFFLRNIPCDLDFKGTQCPNPSSYIPRLLTTNSDHMTFMQRVKNMLYPLALSYICHAFSAPYASLASELFQREVSVVDILSHASVWLFRGDFVMDYPRPIMPNMVFIGGINCANRKPLSQEFEAYINASGEHGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
		Gene Name		UGT1A3
		Uniprot ID		UD13_HUMAN
		KEGG Pathway		hsa:54659
		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:15472229, PubMed:18674515, PubMed:18719240, PubMed:23756265, PubMed:23288867, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:23756265). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229, PubMed:18719240, PubMed:23288867). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3, essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonists losartan, candesartan and zolarsartan, which can inhibit the effect of angiotensin II (PubMed:18674515). Click to Show/Hide
Mechanism Description		Decreased metabolism of Eltrombopag caused by Ospemifene mediated inhibition of UGT

Recommended Action
Management		Until more information is available, caution is advised when ospemifene is used concomitantly with drugs that are substrates of OCT1, UGT1A3, and/or UGT1A9, particularly those with a narrow therapeutic range. Patients should be monitored for the development of adverse effects.

References
1	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2	Product Information. Nexavar (sorafenib). Bayer Pharmaceutical Inc, West Haven, CT.
3	Product Information. Osphena (ospemifene). Shionogi USA Inc, Florham Park, NJ.