Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI6GFOSVH)
  Drug Name Mirtazapine Drug Info Mirabegron Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Urinary Antispasmodics
  Structure

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

Recommended Action
      Management The possibility of prolonged and/or increased pharmacologic effects of mirtazapine should be considered during coadministration of drugs that inhibit CYP450 1A2, 2D6 and/or 3A4. Therapeutic response to mirtazapine should be monitored more closely following initiation, discontinuation, or dosing change of CYP450 inhibitors, and the mirtazapine dosage adjusted as necessary.

References
1 Okubo M, Murayama N, Miura J, Chiba Y, Yamazaki H "Effects of cytochrome P450 2D6 and 3A5 genotypes and possible coadministered medicines on the metabolic clearance of antidepressant mirtazapine in Japanese patients." Biochem Pharmacol 93 (2015): 104-9. [PMID: 25475885]
2 Product Information. Remeron (mirtazapine). Organon, West Orange, NJ.
3 Product Information. Varubi (rolapitant). Tesaro Inc., Waltham, MA.
4 Sitsen JM, Maris FA, Timmer CJ "Concomitant use of mirtazapine and cimetidine: a drug-drug interaction study in healthy male subjects." Eur J Clin Pharmacol 56 (2000): 389-94. [PMID: 11009047]
5 Stormer E, von Moltke LL, Shader RI, Greenblatt DJ "Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4" Drug Metab Dispos 28 (2000): 1168-75. [PMID: 10997935]