No increase in serum digoxin concentration with high-dose diltiazem

Area of Science:

• Pharmacology
• Clinical Pharmacology

Background:

• Digoxin is a cardiac glycoside used for heart failure and arrhythmias.
• Diltiazem is a calcium channel blocker often prescribed with digoxin.
• Potential drug interactions between diltiazem and digoxin require investigation.

Purpose of the Study:

• To evaluate the effect of incremental diltiazem dosing on digoxin pharmacokinetics.
• To assess the safety of concomitant diltiazem and digoxin administration.
• To monitor electrocardiographic and laboratory parameters during the study.

Main Methods:

• Eight healthy volunteers received digoxin 0.25 mg daily.
• Diltiazem dosage was incrementally increased weekly: 120 mg, 240 mg, and 360 mg daily.
• Electrocardiograms, serum drug concentrations, renal function, and electrolytes were measured weekly.

Main Results:

• Concomitant diltiazem up to 360 mg/day did not significantly change trough serum digoxin concentrations.
• A significant decrease in heart rate was observed at the highest diltiazem dose (p<0.05).
• A marginal, non-significant increase in the P-R interval was noted (p=0.08).

Conclusions:

• Diltiazem, at dosages up to 360 mg/day, can be safely administered with low-dose digoxin (0.25 mg/day) in healthy individuals.
• The combination does not lead to clinically significant accumulation of digoxin.
• Monitoring of heart rate and rhythm is advisable when using this drug combination.