Interactions between diaqua(hydrochlorothiazide) and Tikosyn (dofetilide)
hydrochlorothiazide and dofetilide (Major Drug-Drug)
CONTRAINDICATED: Coadministration with hydrochlorothiazide (HCTZ) may increase the plasma concentrations and pharmacodynamic effects of dofetilide. The mechanism of interaction has not been described. Concurrent administration of HCTZ (50 mg once a day) and dofetilide (500 mcg twice a day) for 5 days (following 2 days of diuretic use at half dose) has been shown to increase dofetilide peak plasma concentration (Cmax) by 21% and systemic exposure (AUC) by 27%. However, the QTc increase over time and the maximum QTc increase values went up by 197% and 95%, respectively. In patients who received HCTZ-triamterene (50 mg-100 mg once a day) with dofetilide for 5 days, dofetilide Cmax was increased by 16% and AUC by 30%, while the QTc increase over time and maximum QTc increase values went up by 190% and 84%, respectively. The increased QT prolongation effects can be explained by a combination of the increase in dofetilide exposure and the HCTZ-induced reductions in serum potassium.
MANAGEMENT: Because QT interval prolongation may be associated with serious ventricular arrhythmias such as torsade de pointes tachycardia, use of dofetilide in combination with hydrochlorothiazide is considered contraindicated.
