This panel provides information on interacting drugs and their ADRs along with references
| Interacting drug |
Toxicity |
Interaction Type |
Mechanism |
Reference |
|---|
| Cimetidine (51481-61-9) | Torsade De Pointes | Antagonistic | At least 50% of a dofetilide dose is eliminated unchanged in the urine by
an active renal tubular secretion mechanism.3,4 Drugs that inhibit this
mechanism, such as cimetidine, increase dofetilide plasma levels | Effect of cimetidine and ranitidine on pharmacokinetics and pharmacodynamics of a single dose of dofetilide
|
| Hydrochlorothiazide (58-93-5) | Increase In The Qt Interval | Additive | Hydrochlorothiazide should increase dofetilide levels is unclear. An increase in dofetilide levels would be expected to increase the QT interval, but the increase seen here was much greater than expected by the change in plasma levels | Differentiating Drug-Induced Multichannel Block on the Electrocardiogram: Randomized Study of Dofetilide, Quinidine, Ranolazine, and Verapamil
|
| Ketoconazole (65277-42-1) | Torsade De Pointes | Antagonistic | Ketoconazole may inhibit the active renal tubular secretion mechanism by which dofetilide is eliminated, so reducing its loss from the body. Ketoconazole also inhibits the metabolism of dofetilide by the cytochrome P450 isoenzyme CYP3A4. Both of these mechanisms contribute to the increase in dofetilide
plasma levels. There is a linear relationship between plasma dofetilide concentrations and prolongation of the QT interval, which increases the
risk for torsade de pointes | Dofetilide (Tikosyn): a new drug to control atrial fibrillation
|
| Trimethoprim (738-70-5) | Torsade De Pointes | Antagonistic | Trimethoprim inhibits the active renal tubular
secretion mechanism by which dofetilide is eliminated, so reducing its
loss from the body | Dofetilide (Tikosyn): a new drug to control atrial fibrillation
|
| verapamil (52-53-9) | Torsade De Pointes | Synergistic | Verapamil is postulated to interact with dofetilide by increasing its rate of
absorption by increasing hepatic blood flow. There is a linear relationship
between plasma dofetilide concentrations and prolongation of the QT interval,
which is a risk factor for torsade de pointes | Transient kinetic and dynamic interactions between verapamil and dofetilide, a class III antiarrhythmic
|