Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIXASZM6G)
  Drug Name Rifabutin Drug Info Digitoxin Drug Info
  Drug Type Small molecule Small molecule
  Therapeutic Class Antibiotics Antiarrhythmic Agents
  Structure

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

Recommended Action
      Management While receiving rifampin, the patient should be monitored for inadequate response to digitoxin. Dosage should be increased as necessary. The clinician should consider monitoring the patient for arrhythmia control, signs and symptoms of heart failure, and serum digitoxin concentrations.

References
1 Boman G, Eliasson K, Odar-Cederlof I "Acute cardiac failure during treatment with digoxin--an interaction with rifampicin." Br J Clin Pharmacol 10 (1980): 89-90. [PMID: 7397060]
2 Borcherding SM, Baciewicz AM, Self TH "Update on rifampin drug interactions." Arch Intern Med 152 (1992): 711-6. [PMID: 1558427]
3 Bussey HI, Merritt GJ, Hill EG "The influence of rifampin on quinidine and digoxin." Arch Intern Med 144 (1984): 1021-3. [PMID: 6712395]
4 Novi C, Bissoli F, Simonati V, Volpini T, Baroli A, Vignati G "Rifampin and digoxin: possible drug interaction in a dialysis patient." JAMA 244 (1980): 2521-2. [PMID: 7431585]
5 Poor DM, Self TH, Davis HL "Interaction of rifampin and digitoxin." Arch Intern Med 143 (1983): 599. [PMID: 6830398]
6 Product Information. Rifadin (rifampin). Hoechst Marion-Roussel Inc, Kansas City, MO.
7 Strayhorn VA, Baciewicz AM, Self TH "Update on rifampin drug interactions, III." Arch Intern Med 157 (1997): 2453-8. [PMID: 9385296]
8 Venkatesan K "Pharmacokinetic drug interactions with rifampicin." Clin Pharmacokinet 22 (1992): 47-65. [PMID: 1559307]