Details of Drug Interaction | MecDDI

Drug General Information (ID: DDIAEC348Y)
Drug Name			Mirabegron		Drug Info		Venetoclax		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Urinary Antispasmodics				Antineoplastics
Structure

Mechanism of Mirabegron-Venetoclax Interaction (Severity Level: Major)
Transporter inhibition Click to Show/Hide Mechanism Graph

Drug Name		Mirabegron				Venetoclax
Mechanism		P-gp inhibitor				P-gp substrate
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 Venetoclax due to the transporter inhibition by Mirabegron

Recommended Action
Management		Concomitant use of venetoclax with P-gp inhibitors should generally be avoided. If coadministration is required, the manufacturer recommends that venetoclax dosage be reduced by at least 50%. The dosage used prior to initiating the P-gp inhibitor may be resumed 2 to 3 days after discontinuation of the inhibitor.

References
1	Cerner Multum, Inc. "Australian Product Information.".
2	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3	Product Information. Venclexta (venetoclax). AbbVie US LLC, North Chicago, IL.