BLACK BOX WARNING
- serious ventricular arrhythmias (TdP); initiation requires hospitalization with continuous ECG monitoring for at least 3 days (REMS program)
dofetilide
Brand: Tikosyn
⚠ BBW ISMP High Alert Prototype: amiodarone
Drug Class: antiarrhythmic (Class III)
Drug Family: antiarrhythmic
Subclass: selective IKr potassium channel blocker
Organ Systems: cardiovascular
Mechanism of Action
Selectively blocks the IKr potassium channel, prolonging the cardiac action potential and effective refractory period uniformly across the myocardium. Has no effect on sodium or calcium channels or adrenergic receptors.
IKr (rapid delayed rectifier potassium channel)
Indications
- atrial fibrillation/flutter (conversion to and maintenance of sinus rhythm)
Contraindications
- QTc >440ms (or >500ms in ventricular conduction abnormalities)
- CrCl <20 mL/min
- congenital or acquired long QT syndrome
- concurrent use of verapamil, cimetidine, trimethoprim, ketoconazole, or megestrol
Adverse Effects
Common
- QT prolongation
- headache
- chest pain
- dizziness
Serious
- torsades de pointes (dose-dependent, up to 3%)
- ventricular fibrillation
- proarrhythmia
Pharmacokinetics (ADME)
| Absorption | >90% oral bioavailability |
| Distribution | moderate (Vd ~3 L/kg) |
| Metabolism | minimal hepatic metabolism (CYP3A4 minor); primarily excreted unchanged |
| Excretion | renal (80% unchanged) |
| Half-life | 10 hours |
| Onset | 2-3 hours |
| Peak | 2-3 hours |
| Duration | ~12 hours |
| Protein Binding | 60-70% |
| Vd | 3 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| verapamil | inhibits renal tubular secretion of dofetilide — increases dofetilide levels; contraindicated | contraindicated |
| cimetidine | inhibits renal tubular secretion — significantly increases dofetilide exposure; contraindicated | contraindicated |
| trimethoprim | inhibits renal tubular secretion (cation transport) — increases dofetilide levels; contraindicated | contraindicated |
| QT-prolonging drugs | additive QT prolongation and TdP risk | major |
| thiazide diuretics | hypokalemia amplifies QT prolongation | major |
Nursing Considerations
- REMS program: initiation requires minimum 3-day in-hospital stay with continuous cardiac monitoring and QTc assessment before each dose
- QTc monitoring: measure 2–3 hours after each dose during initiation — if QTc increases >15% or exceeds 500ms, dose must be reduced or discontinued
- Renal dosing is mandatory: dose is based on CrCl; do not use if CrCl <20 mL/min
- Correct hypokalemia and hypomagnesemia before and during therapy
- Educate patient about all interacting drugs — including OTC (cimetidine) and antibiotics (trimethoprim)
Clinical Pearls
- Only antiarrhythmic approved specifically for AF/flutter with a structured REMS safety program requiring in-hospital initiation
- Unlike amiodarone, dofetilide has no extra-cardiac toxicity — all risk is proarrhythmia (TdP)
- Purely renally cleared — dose adjustments are mandatory and based on CrCl tiers (500mcg, 250mcg, or 125mcg BID)
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.