Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIBZRQWX8)
Drug Name			Bosutinib		Drug Info		Voxilaprevir		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antineoplastics				Antiviral Agents
Structure

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

Drug Name		Bosutinib				Voxilaprevir
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 Bosutinib due to the transporter inhibition by Voxilaprevir

Recommended Action
Management		Caution is advised when bosutinib is used with CYP450 3A4 or P-gp inhibitors. Patients should be monitored more closely for development of adverse effects such as diarrhea, nausea, vomiting, abdominal pain, myelosuppression, hepatotoxicity, and fluid retention (e.g., pericardial effusion, pleural effusion, pulmonary edema, peripheral edema).

References
1	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2	Product Information. Bosulif (bosutinib). Pfizer U.S. Pharmaceuticals Group, New York, NY.