Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIYKJU207)
  Drug Name Fluoxetine Drug Info Anisindione Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antidepressants Anticoagulants
  Structure

 Mechanism of Fluoxetine-Anisindione Interaction (Severity Level: Moderate)
     Competitive binding of plasma proteins Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Fluoxetine Anisindione
      Mechanism 1 Competition for plasma protein binding sites Competition for plasma protein binding sites
      Key Mechanism Factor 1
Factor Name Plasma protein binding
Factor Description Plasma protein binding refers to the degree of binding of a drug to proteins in the blood, and the lower the degree of binding, the more efficiently the drug can cross cell membranes or diffuse. Plasma protein binding alters the distribution and therapeutic characteristics of the drugs.
      Mechanism Description
  • Increased plasma concentration of Anisindione and Fluoxetine due to competitive binding of plasma proteins
     CYP450 enzyme inhibition Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Fluoxetine Anisindione
      Mechanism 2 CYP450 2C9 inhibitor CYP450 2C9 substrate
      Key Mechanism Factor 2
Factor Name Cytochrome P450 2C9
×
Structure Sequence
MDSLVVLVLCLSCLLLLSLWRQSSGRGKLPPGPTPLPVIGNILQIGIKDISKSLTNLSKVYGPVFTLYFGLKPIVVLHGYEAVKEALIDLGEEFSGRGIFPLAERANRGFGIVFSNGKKWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFHKRFDYKDQQFLNLMEKLNENIKILSSPWIQICNNFSPIIDYFPGTHNKLLKNVAFMKSYILEKVKEHQESMDMNNPQDFIDCFLMKMEKEKHNQPSEFTIESLENTAVDLFGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRSHMPYTDAVVHEVQRYIDLLPTSLPHAVTCDIKFRNYLIPKGTTILISLTSVLHDNKEFPNPEMFDPHHFLDEGGNFKKSKYFMPFSAGKRICVGEALAGMELFLFLTSILQNFNLKSLVDPKNLDTTPVVNGFASVPPFYQLCFIPV
Gene Name CYP2C9
Uniprot ID CP2C9_HUMAN
KEGG Pathway hsa:1559
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, 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:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:7574697, PubMed:15766564, PubMed:19965576, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9866708, PubMed:9435160). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031).
    Click to Show/Hide
      Mechanism Description
  • Decreased metabolism of Anisindione caused by Fluoxetine mediated inhibition of CYP450 enzyme
     Increased risk of bleeding Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Fluoxetine Anisindione
      Mechanism 3 Risk of bleeding
Antiplatelet effects  		Risk of bleeding
Anticoagulant 
      Key Mechanism Factor 3
Factor Name Bleeding
Factor Description Patients may be at risk for bleeding when the outcome of a disease or disease treatment confounds the standard mechanisms for maintaining hemostasis. Signs or symptoms of abnormal bleeding include: bleeding that takes a long time to stop (including nosebleeds, bleeding gums, bleeding from cuts and abrasions, and menstrual bleeding); severe unexplained bruising, or bruising that becomes larger; blood in the urine or stool, etc.
      Mechanism Description
  • Increased risk of bleeding by the combination of Fluoxetine and Anisindione 

Recommended Action
      Management Close clinical and laboratory monitoring for altered anticoagulant effect is recommended if oral anticoagulants and fluoxetine must be used together. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

References
1 Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7. [PMID: 2198298]
2 Claire RJ, Servis ME, Cram DL Jr "Potential interaction between warfarin sodium and fluoxetine." Am J Psychiatry 148 (1991): 1604. [PMID: 1928485]
3 Dent LA, Orrock MW "Warfarin-fluoxetine and diazepam-fluoxetine interaction." Pharmacotherapy 17 (1997): 170-2. [PMID: 9017779]
4 Ford MA, Anderson ML, Rindone JP, Jaskar DW "Lack of effect of fluoxetine on the hypoprothrombinemic response of warfarin." J Clin Psychopharmacol 17 (1997): 110-2. [PMID: 10950474]
5 Product Information. Prozac (fluoxetine). Dista Products Company, Indianapolis, IN.
6 Thijssen HH, Flin ois JP, Beaune PH "Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions in human liver microsomes." Drug Metab Dispos 28 (2000): 1284-90. [PMID: 11038154]
7 Woolfrey S, Gammack NS, Dewar MS, Brown PJ "Fluoxetine-warfarin interaction." BMJ 307 (1993): 241. [PMID: 8369688]