Details of Drug Interaction | MecDDI

Drug General Information (ID: DDINHUXI0P)
Drug Name			Aliskiren		Drug Info		Daclatasvir		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Ns5A Inhibitors
Structure

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

Drug Name		Aliskiren				Daclatasvir
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 Aliskiren due to the transporter inhibition by Daclatasvir

Recommended Action
Management		Pharmacologic response to aliskiren should be monitored more closely whenever a CYP450 3A4 and/or P-gp inhibitor is added to or withdrawn from therapy, and the aliskiren dosage adjusted if necessary. Patients should be advised to notify their physician if they experience excessive adverse effects of aliskiren such as dizziness, lightheadedness, diarrhea, abdominal pain, and gastroesophageal reflux.

References
1	Canadian Pharmacists Association.
2	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3	Product Information. Tekturna (aliskiren). Novartis Pharmaceuticals, East Hanover, NJ.
4	Tapaninen T, Backman JT, Kurkinen K, Neuvonen P, Niemi M "Itraconazole, a P-glycoprotein and CYP3A4 inhibitor, markedly raises the plasma concentrations and enhances the renin-inhibiting effect of aliskiren." J Clin Pharmacol 51 (2011): 359-67. [PMID: 20400651]