Details of Drug Interaction | MecDDI

Drug General Information (ID: DDI86U7QG2)
Drug Name			Edoxaban		Drug Info		Brigatinib		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anticoagulants/Factor Xa Inhibitors				Multikinase Inhibitors
Structure

Mechanism of Edoxaban-Brigatinib Interaction (Severity Level: Moderate)
Transporter inhibition Click to Show/Hide Mechanism Graph

Drug Name		Edoxaban				Brigatinib
Mechanism		P-gp substrate				P-gp inhibitor
Key Mechanism Factor 1
		Factor Name		P-glycoprotein 1				× Structure Sequence MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAIIHGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSGIGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVSKINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFTDKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIGAAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARGAAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSGQTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLFATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIAIARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAGFDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRSSLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAIINGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKAGEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNIANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGSGKIATEAIENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFGAYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDSYSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVVQLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVVSQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLDEATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQLLAQKGIYFSMVSVQAGTKRQ
		Gene Name		ABCB1
		Uniprot ID		MDR1_HUMAN
		KEGG Pathway		hsa:5243
		Protein Family		ABC transporter superfamily
		Protein Function		Translocates drugs and phospholipids across the membrane (PubMed:8898203, PubMed:2897240, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:9038218). Click to Show/Hide
Mechanism Description		Decreased clearance of Edoxaban due to the transporter inhibition by Brigatinib

Recommended Action
Management		Caution is advised if brigatinib is used concomitantly with drugs that are substrates of P-gp, BCRP, OCT 1, MATE 1, and/or MATE 2K transport proteins, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever brigatinib 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. Alunbrig (brigatinib). Ariad Pharmaceuticals Inc, Cambridge, MA.
3	Product Information. Lonsurf (tipiracil-trifluridine). Taiho Oncology, Inc., Princeton, NJ.