Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIBE3Z28O)
  Drug Name Dextromethorphan Drug Info Givosiran Drug Info
  Drug Type Small molecule Small interfering RNA
  Therapeutic Class Analgesics Metabolic Agents
  Structure

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

Recommended Action
      Management Caution should be exercised if these drugs must be used together. Patients should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required.

References
1 Cerner Multum, Inc. "Australian Product Information.".
2 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
3 Funck-Brentano C, Jacqz-Aigrain E, Leenhardt A, Roux A, Poirier JM, Jaillon P "Influence of amiodarone on genetically determined drug metabolism in humans." Clin Pharmacol Ther 50 (1991): 259-66. [PMID: 1914360]
4 Product Information. Farydak (panobinostat). Novartis Pharmaceuticals, East Hanover, NJ.
5 Product Information. Qelbree (viloxazine). Supernus Pharmaceuticals Inc, Rockville, MD.
6 Product Information. Zytiga (abiraterone). Centocor Inc, Malvern, PA.