OBJECT DRUGS

• Dofetilide (Tikosyn)

PRECIPITANT DRUGS

Inhibitors of Cationic Tubular Secretion:

• Cimetidine (Tagamet, etc.)
• Dolutegravir (Tivicay)
• Ketoconazole (Nizoral, etc.)
• Megestrol (Megace)
• Triamterene (Dyrenium)
• Trimethoprim (Bactrim, Septra)
• Verapamil (Isoptin, etc.)

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, diltiazem, disopyramide, metformin, procainamide and quinidine) should be used only with careful monitoring in patients taking dofetilide. Ketoconazole substantially increases dofetilide concentrations (especially in females), ketoconazole is listed as contraindicated in the dofetilide label. The mechanism of the ketoconazole interaction is not clear, but inhibition of the CYP3A4 metabolism of dofetilide may be one factor. Verapamil increased peak dofetilide concentrations, and the combination was associated with a higher risk of Torsade de Pointes in one study. Verapamil is also contraindicated in the dofetilide label, although the evidence of increased risk is not firmly established.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• Cimetidine: Other H₂-receptor antagonists such as famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) could be used instead of cimetidine. The dofetilide label states that neither ranitidine nor omeprazole affects dofetilide pharmacokinetics.
• 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.