Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIOCBGTAD)
Drug Name			Eltrombopag		Drug Info		Tafamidis		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Platelet-Stimulating Agents				Transthyretin Stabilizers
Structure

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

Drug Name		Eltrombopag				Tafamidis
Mechanism		UGT1A1 substrate				UGT1A1 inhibitor
Key Mechanism Factor 1
		Factor Name		UDP-glucuronosyltransferase 1A1				× Structure Sequence MAVESQGGRPLVLGLLLCVLGPVVSHAGKILLIPVDGSHWLSMLGAIQQLQQRGHEIVVLAPDASLYIRDGAFYTLKTYPVPFQREDVKESFVSLGHNVFENDSFLQRVIKTYKKIKKDSAMLLSGCSHLLHNKELMASLAESSFDVMLTDPFLPCSPIVAQYLSLPTVFFLHALPCSLEFEATQCPNPFSYVPRPLSSHSDHMTFLQRVKNMLIAFSQNFLCDVVYSPYATLASEFLQREVTVQDLLSSASVWLFRSDFVKDYPRPIMPNMVFVGGINCLHQNPLSQEFEAYINASGEHGIVVFSLGSMVSEIPEKKAMAIADALGKIPQTVLWRYTGTRPSNLANNTILVKWLPQNDLLGHPMTRAFITHAGSHGVYESICNGVPMVMMPLFGDQMDNAKRMETKGAGVTLNVLEMTSEDLENALKAVINDKSYKENIMRLSSLHKDRPVEPLDLAVFWVEFVMRHKGAPHLRPAAHDLTWYQYHSLDVIGFLLAVVLTVAFITFKCCAYGYRKCLGKKGRVKKAHKSKTH
		Gene Name		UGT1A1
		Uniprot ID		UD11_HUMAN
		KEGG Pathway		hsa:54658
		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		Decreased metabolism of Eltrombopag caused by Tafamidis mediated inhibition of UGT

Recommended Action
Management		Caution is advised if tafamidis is used concomitantly with drugs that are substrates of these transport proteins, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever tafamidis is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

References
1	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2	Product Information. Vyndaqel (tafamidis). Pfizer U.S. Pharmaceuticals Group, New York, NY.
3	Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA."