OBJECT DRUGS

• Dofetilide (Tikosyn)

PRECIPITANT DRUGS

Inhibitors of Cationic Tubular Secretion:

• Cimetidine (Tagamet, etc.)
• Ketoconazole (Nizoral, etc.)
• Triamterene (Dyrenium)
• Trimethoprim (Bactrim, Septra)

Comment:

Approximately 70% of dofetilide is renally eliminated unchanged via active cationic secretion and glomerular filtration. Dofetilide-induced QTc prolongation increases with increasing plasma concentrations. Any drug known to compete for cationic secretion could result in an increase in dofetilide plasma concentration. Pending more study, other drugs reported to inhibit cationic tubular secretion (e.g., amiodarone, procainamide, diltiazem, metformin, and verapamil) should be used only with careful monitoring in patients taking dofetilide. Verapamil and ketoconazole also may inhibit the CYP3A4 metabolism of dofetilide.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Cimetidine: Other H₂-receptor antagonists such as famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) could be used instead of cimetidine.
• Triamterene: Spironolactone (Aldactone) or amiloride (Midamor) could be used as a potassium-sparing diuretic.
• Monitor: Patients taking dofetilide should be carefully monitored for increased QTc intervals if drugs that reduce its renal clearance are coadministered.