Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDI41LPRG3)
  Drug Name Rifabutin Drug Info Warfarin Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antibiotics Anticoagulants
  Structure

 Mechanism of Rifabutin-Warfarin Interaction (Severity Level: Major)
     CYP450 enzyme induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name Rifabutin Warfarin
      Mechanism CYP450 inducer CYP450 substrate
      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
  • Increased metabolism of Warfarin caused by Rifabutin mediated induction of CYP450 enzyme

Recommended Action
      Management Concurrent use should be avoided unless no alternatives are available. The INR or prothrombin time should be monitored closely during concomitant therapy and after rifampin is discontinued. Adjustments in warfarin dosage may be needed when rifampin dosage is added, discontinued, or changed. This interaction may occur with other oral anticoagulants and with rifabutin.

References
1 Rifampin.?Tuberculosis (Edinb). 2008;88(2):151-154. doi:10.1016/S1472-9792(08)70024-6. [PMID: 18486058]
2 Borcherding SM, Baciewicz AM, Self TH "Update on rifampin drug interactions." Arch Intern Med 152 (1992): 711-6. [PMID: 1558427]
3 Casner PR "Inability to attain oral anticoagulation: warfarin-rifampin interaction revisited." South Med J 89 (1996): 1200-3. [PMID: 8969357]
4 Heimark LD, Gibaldi M, Trager WF, et al "The mechanism of the warfarin-rifampin drug interaction in humans." Clin Pharmacol Ther 42 (1987): 388-94. [PMID: 3665337]
5 Heimark LD, Gilbaldi M, Trager WF, et al "The mechanism of the warfarin-rifampin drug interaction in humans." Clin Pharmacol Ther 42 (1987): 388-94. [PMID: 3665337]
6 O'Reilly RA "Interaction of chronic daily warfarin therapy and rifampin." Ann Intern Med 83 (1975): 506-8. [PMID: 1166982]
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8 Self TH, Mann RB "Interaction of rifampin and warfarin." Chest 4 (1975): 490-1. [PMID: 1122784]
9 Strayhorn VA, Baciewicz AM, Self TH "Update on rifampin drug interactions, III." Arch Intern Med 157 (1997): 2453-8. [PMID: 9385296]
10 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]
11 Venkatesan K "Pharmacokinetic drug interactions with rifampicin." Clin Pharmacokinet 22 (1992): 47-65. [PMID: 1559307]
12 Wells PS, Holbrook AM, Crowther NR, Hirsh J "Interactions of warfarin with drugs and food." Ann Intern Med 121 (1994): 676-83. [PMID: 7944078]