Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI960VAYK)
  Drug Name Norethisterone Drug Info Mifepristone Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Contraceptive Agents Uterotonic Agents
  Structure

 Mechanism of Norethisterone-Mifepristone Interaction (Severity Level: Moderate)
     Attenuated pharmacological effects (Unspecific) Click to Show/Hide Mechanism Graph
      Drug Name Norethisterone Mifepristone
      Mechanism Progesterone receptor agonist Progesterone receptor antagonist
      Key Mechanism Factor 1
Factor Name Progesterone receptor
×
Structure Sequence
MTELKAKGPRAPHVAGGPPSPEVGSPLLCRPAAGPFPGSQTSDTLPEVSAIPISLDGLLFPRPCQGQDPSDEKTQDQQSLSDVEGAYSRAEATRGAGGSSSSPPEKDSGLLDSVLDTLLAPSGPGQSQPSPPACEVTSSWCLFGPELPEDPPAAPATQRVLSPLMSRSGCKVGDSSGTAAAHKVLPRGLSPARQLLLPASESPHWSGAPVKPSPQAAAVEVEEEDGSESEESAGPLLKGKPRALGGAAAGGGAAAVPPGAAAGGVALVPKEDSRFSAPRVALVEQDAPMAPGRSPLATTVMDFIHVPILPLNHALLAARTRQLLEDESYDGGAGAASAFAPPRSSPCASSTPVAVGDFPDCAYPPDAEPKDDAYPLYSDFQPPALKIKEEEEGAEASARSPRSYLVAGANPAAFPDFPLGPPPPLPPRATPSRPGEAAVTAAPASASVSSASSSGSTLECILYKAEGAPPQQGPFAPPPCKAPGASGCLLPRDGLPSTSASAAAAGAAPALYPALGLNGLPQLGYQAAVLKEGLPQVYPPYLNYLRPDSEASQSPQYSFESLPQKICLICGDEASGCHYGVLTCGSCKVFFKRAMEGQHNYLCAGRNDCIVDKIRRKNCPACRLRKCCQAGMVLGGRKFKKFNKVRVVRALDAVALPQPVGVPNESQALSQRFTFSPGQDIQLIPPLINLLMSIEPDVIYAGHDNTKPDTSSSLLTSLNQLGERQLLSVVKWSKSLPGFRNLHIDDQITLIQYSWMSLMVFGLGWRSYKHVSGQMLYFAPDLILNEQRMKESSFYSLCLTMWQIPQEFVKLQVSQEEFLCMKVLLLLNTIPLEGLRSQTQFEEMRSSYIRELIKAIGLRQKGVVSSSQRFYQLTKLLDNLHDLVKQLHLYCLNTFIQSRALSVEFPEMMSEVIAAQLPKILAGMVKPLLFHKK
Gene Name PGR NR3C3
Uniprot ID PRGR_HUMAN
KEGG Pathway hsa:5241
Protein Family Nuclear hormone receptor family, NR3 subfamily
Protein Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor.; FUNCTION: [Isoform A]: Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of corepressor NCOR2. ; FUNCTION: [Isoform B]: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation. ; FUNCTION: [Isoform 4]: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
    Click to Show/Hide
      Mechanism Description
  • Attenuated pharmacological effects of  Norethisterone when combined with Mifepristone 

Recommended Action
      Management When mifepristone is prescribed daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, only nonhormonal contraceptive methods should be used. Because mifepristone is eliminated slowly from the body, drug interactions may be observed for a prolonged period following discontinuation (approximately 2 to 3 weeks if mifepristone had been administered chronically to steady state).

References
1 Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8. [PMID: 8162660]
2 Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
3 Product Information. Korlym (mifepristone). Corcept Therapeutics Incorporated, Menlo Park, CA.