Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIF71UPJL)
  Drug Name Amiodarone Drug Info Emapalumab Drug Info
  Drug Type Small molecule Monoclonal antibody
  Therapeutic Class Antiarrhythmic Agents Selective Immunosuppressants

 Mechanism of Amiodarone-Emapalumab Interaction (Severity Level: Moderate)
     Altered formation of CYP450 enzymes Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Amiodarone Emapalumab
      Mechanism CYP450 substrate Alter the formation of CYP450 enzymes
      Key Mechanism Factor 1
Factor Name Cytochrome P450 Structure Sequence
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:20702771, PubMed:19965576, PubMed:21490593, 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). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:2732228, PubMed:14559847, PubMed:12865317, PubMed:15373842, PubMed:15764715, PubMed:21576599, PubMed:21490593). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:14559847, PubMed:12865317). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:2732228, PubMed:15373842, PubMed:15764715, PubMed:22773874). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:2732228, PubMed:15373842, PubMed:15764715). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981).
    Click to Show/Hide
      Mechanism Description
  • Altered metabolism of Amiodarone due to Emapalumab alters the formation of CYP450 enzymes

Recommended Action
      Management Caution is advised when treatments targeting cytokines such as interleukins, tumor necrosis factors, or interferons are prescribed to patients receiving concomitant drugs that are CYP450 substrates, particularly those with narrow therapeutic ranges (e.g., antiarrhythmics, anticonvulsants, immunosuppressants, theophylline) or sensitive substrates where decreases in plasma levels may be significant or undesirable (e.g., oral contraceptives, statins, benzodiazepines, opioids). Clinical and/or laboratory monitoring should be considered following the initiation or withdrawal of such treatments, and the dosage(s) of the CYP450 substrate(s) adjusted accordingly. The effects of IL inhibitors, TNF blockers, and IFN inhibitors on CYP450 activities may persist for several weeks after stopping therapy.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 Product Information. Actemra (tocilizumab). Genentech, South San Francisco, CA.
3 Product Information. Amevive (alefacept). Biogen, Cambridge, MA.
4 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
5 Product Information. Cosentyx (secukinumab). Novartis Pharmaceuticals, East Hanover, NJ.
6 Product Information. Gamifant (emapalumab). Sobi Inc, Ardmore, PA.
7 Product Information. Ilaris (canakinumab). Novartis Pharmaceuticals, East Hanover, NJ.
8 Product Information. Ilumya (tildrakizumab). Merck & Company Inc, Whitehouse Station, NJ.
9 Product Information. Kevzara (sarilumab). sanofi-aventis, Bridgewater, NJ.
10 Product Information. Remicade (infliximab). Centocor Inc, Malvern, PA.
11 Product Information. Simponi (golimumab). Centocor Inc, Malvern, PA.
12 Product Information. Skyrizi (risankizumab). AbbVie US LLC, North Chicago, IL.
13 Product Information. Stelara (ustekinumab). Centocor Inc, Malvern, PA.
14 Product Information. Sylvant (siltuximab). Janssen Biotech, Inc., Horsham, PA, PA.
15 Product Information. Taltz Autoinjector (ixekizumab). Eli Lilly and Company, Indianapolis, IN.