Drug General Information (ID: DDIUA8FDP2)
  Drug Name Docetaxel Drug Info Simeprevir Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antineoplastics Antiinfective Agents
  Structure

 Mechanism of Docetaxel-Simeprevir Interaction (Severity Level: Moderate)
     Transporter inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Docetaxel Simeprevir
      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 Docetaxel due to the transporter inhibition by Simeprevir 

Recommended Action
      Management The possibility of prolonged and/or increased pharmacologic effects of paclitaxel or docetaxel therapy should be considered during coadministration with P-gp inhibitors, including adverse effects such as myelosuppression, stomatitis, neurotoxicity (e.g., paraesthesia, dysesthesia, pain), myalgia, asthenia, fluid retention, nausea, vomiting, and diarrhea. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a P-gp inhibitor is added to or withdrawn from therapy.

References
1 Aronson JK, Grahame-Smith DG "Clinical pharmacology: adverse drug interactions." Br Med J 282 (1981): 288-91. [PMID: 6779990]
2 Cerner Multum, Inc. "Australian Product Information.".
3 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
4 Engels FK, Mathot RA, Loos WJ, van Schaik RH, Verweij J "Influence of high-dose ketoconazole on the pharmacokinetics of docetaxel." Cancer Biol Ther 5 (2006): 833-9. [PMID: 16775418]
5 McInnes GT, Brodie MJ "Drug interactions that matter: a critical reappraisal." Drugs 36 (1988): 83-110. [PMID: 3063497]
6 Product Information. Taxotere (docetaxel). Rhone-Poulenc Rorer, Collegeville, PA.
7 Starr SP, Hammann F, Gotta V, et al. "Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity." Br J Clin Pharmacol 450 (2016): 22-27. [PMID: 27868228]
8 Vodovar D, Arnaout M, Mongardon N, et al. "Severe docetaxel overdose induced by pharmacokinetic interaction with dronedarone." J Clin Oncol 29 (2011): e694-5. [PMID: 21730272]
9 Yong WP, Wang LZ, Tham LS, et al. "A phase I study of docetaxel with ketoconazole modulation in patients with advanced cancers." Cancer Chemother Pharmacol 62 (2008): 243-51. [PMID: 17909805]