Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIYOVKFM1)
  Drug Name Tamsulosin Drug Info Lorcaserin Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antineoplastics Anorexiants
  Structure

 Mechanism of Tamsulosin-Lorcaserin Interaction (Severity Level: Moderate)
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Tamsulosin Lorcaserin
      Mechanism CYP450 2D6 substrate CYP450 2D6 inhibitor
      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 Tamsulosin caused by Lorcaserin mediated inhibition of CYP450 enzyme

Recommended Action
      Management Caution is advised if tamsulosin is used concomitantly with moderate CYP450 3A4 inhibitors (e.g., amiodarone, aprepitant, diltiazem, dronedarone, erythromycin, fluconazole, fluvoxamine, fusidic acid, imatinib, isavuconazonium, verapamil) and/or moderate to potent CYP450 2D6 inhibitors (e.g., abiraterone, bupropion, celecoxib, cinacalcet, darifenacin, dronedarone, duloxetine, fluoxetine, lorcaserin, paroxetine, propafenone, quinidine, ranolazine, rolapitant, terbinafine), particularly at a dosage higher than 0.4 mg/day. The potential for increased risk of adverse effects such as postural hypotension, syncope, and priapism should be considered.

References
1 Franco-Salinas G, de la Rosette JJ, Michel MC "Pharmacokinetics and pharmacodynamics of tamsulosin in its modified-release and oral controlled absorption system formulations." Clin Pharmacokinet 49 (2010): 177-88. [PMID: 20170206]
2 Kamimura H, Oishi S, Matsushima H, et al. "Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes." Xenobiotica 28 (1998): 909-22. [PMID: 9849639]
3 Product Information. Flomax (tamsulosin). Boehringer-Ingelheim, Ridgefield, CT.
4 Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.