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Drug Interactions between digoxin and dofetilide

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

digoxin dofetilide

Applies to: digoxin and dofetilide

MONITOR: Concomitant administration of digoxin and dofetilide has been associated with a higher occurrence of torsade de pointes arrhythmia than dofetilide alone. It is not clear whether this finding represents an interaction between the drugs or the presence of more severe structural heart disease, a known risk factor for arrhythmia, in patients on digoxin. However, no increase in mortality has been observed in patients taking this combination. In a pharmacokinetic study, dofetilide (250 mcg twice daily for 5 days) had no significant effect on the steady-state pharmacokinetics of digoxin (250 mcg once daily) in healthy volunteers compared to placebo.

MANAGEMENT: Clinicians should be aware of the potential for increased risk of torsade de pointes when dofetilide is administered in patients treated with digoxin.

References (2)
  1. (2001) "Product Information. Tikosyn (dofetilide)." Pfizer U.S. Pharmaceuticals
  2. Kleinermans D, Nichols DJ, Dalrymple I (2001) "Effect of Dofetilide on the pharmacokinetics of digoxin." Am J Cardiol, 87, 248+

Drug and food interactions

Minor

digoxin food

Applies to: digoxin

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.

References (2)
  1. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  2. Becquemont L, Verstuyft C, Kerb R, et al. (2001) "Effect of grapefruit juice on digoxin pharmacokinetics in humans." Clin Pharmacol Ther, 70, p. 311-6
Minor

dofetilide food

Applies to: dofetilide

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.

References (1)
  1. (2001) "Product Information. Tikosyn (dofetilide)." Pfizer U.S. Pharmaceuticals

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antiarrhythmics' category:

  • digoxin
  • dofetilide

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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