Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIBARZ6ON)
  Drug Name Dextropropoxyphene Drug Info Tamoxifen Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Analgesics Antineoplastics
  Structure

 Mechanism of Dextropropoxyphene-Tamoxifen Interaction (Severity Level: Major)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Dextropropoxyphene Tamoxifen
      Mechanism CYP450 2D6 inhibitor CYP450 2D6 substrate
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2D6
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Structure Sequence
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQLRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVFLARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDKAVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKVLRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVADLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVIHEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHFLDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGVFAFLVSPSPYELCAVPR
Gene Name CYP2D6
Uniprot ID CP2D6_HUMAN
KEGG Pathway hsa:1565
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Tamoxifen caused by Dextropropoxyphene mediated inhibition of CYP450 enzyme

Recommended Action
      Management Based on available data, patients treated with tamoxifen should avoid the chronic use of potent CYP450 2D6 inhibitors such as fluoxetine, paroxetine, and quinidine whenever possible, and preferably also moderate inhibitors such as bupropion, duloxetine, and sertraline. If an antidepressant is required during treatment with tamoxifen, agents such as desvenlafaxine, fluvoxamine, milnacipran, levomilnacipran, mirtazapine, and venlafaxine may be considered, since they have mild to no effects on CYP450 2D6. alternatively, aromatase inhibitors such as anastrozole, exemestane, and letrozole may be appropriate substitutes for tamoxifen in certain patients. alternatively, aromatase inhibitors such as anastrozole, exemestane, and letrozole may be appropriate substitutes for tamoxifen in certain patients.

References
1 Goetz MP, Rae JM, Suman VJ, et al. "Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes." J Clin Oncol 23 (2005): 9312-8. [PMID: 16361630]
2 Schroth W, Antoniadou L, Fritz P, et al. "Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes." J Clin Oncol 25 (2007): 5187-93. [PMID: 18024866]
3 Stearns V, Johnson MD, Rae JM, et al. "Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine." J Natl Cancer Inst 95 (2003): 1758-64. [PMID: 14652237]