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Itraconazole increases serum digoxin concentration

J Partanen1, K M Jalava, P J Neuvonen

  • 1Department of Medicine, University of Helsinki, Finland.

Pharmacology & Toxicology
|November 1, 1996
PubMed
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Itraconazole significantly increases serum digoxin concentrations, potentially leading to toxicity. This drug interaction necessitates caution when prescribing itraconazole to patients already taking digoxin.

Area of Science:

  • Pharmacology
  • Drug Interactions
  • Clinical Pharmacy

Background:

  • Itraconazole is known to inhibit drug metabolism via cytochrome P450 (CYP) enzymes.
  • Several drugs that increase serum digoxin levels are CYP inhibitors.
  • Case reports suggest itraconazole may induce digoxin toxicity when co-administered.

Purpose of the Study:

  • To investigate the potential pharmacokinetic interaction between itraconazole and digoxin.
  • To quantify the effect of itraconazole on serum digoxin concentrations in healthy volunteers.

Main Methods:

  • A double-blind, randomized, cross-over study involving ten healthy volunteers.
  • Participants received 0.25 mg digoxin daily for 20 days, with either 200 mg itraconazole or placebo daily for 10 days.

Related Experiment Videos

  • Serum concentrations of digoxin and itraconazole were measured at multiple time points.

    • Main Results:

    • Itraconazole significantly increased mean serum digoxin concentration from 1.0 +/- 0.1 nmol/l to 1.8 +/- 0.1 nmol/l (P < 0.001) on day 10.
    • This increase was observed in all study participants.
    • The mechanism may involve CYP3A4-mediated pharmacokinetic changes.

    Conclusions:

    • Itraconazole administration leads to a significant elevation in serum digoxin levels.
    • Healthcare providers should exercise caution when prescribing itraconazole to patients on digoxin therapy.
    • Monitoring digoxin levels is advisable in patients co-treated with itraconazole.