Dofetilide
- Atc Codes:C01BD04
- CAS Codes:115256-11-6
- PHARMGKB ID:115256-11-6
Table of contents
- Brand Names
- Chemistry
- Pharmacologic Category
- Mechanism of Action
- Therapeutic Use
- Pregnancy and Lactation Implications
- Contraindications
- Warnings and Precautions
- Adverse Reactions
- Caution and personalized dose adjustment in patients with the following genotypes
- Other genes that may be involved
- Substrate of
- Drug Interactions
- Nutrition/Nutraceutical Interactions
- Dosage
- Pharmacokinetics and Pharmacodynamics
- Special Considerations
Brand Names
North America
USA: Tikosyn.
Drug combinations
Chemistry
Dofetilide: C~19~H~27~N~3~O~5~S~2~. Mw: 441.56. (1) Methanesulfonamide, N-[4-[2-[methyl[2-[4-[(methylsulfonyl)amino]phenoxy]ethyl]amino]ethyl]phenyl]-; (2) β-[(p-Methanesulfonamidophenethyl)methylamino]methanesulfono-p-phenetidide. CAS-115256-11-6 (1993).
Pharmacologic Category
Antiarrhythmic Agents; Class III Antiarrhythmics. (ATC-Code: C01BD04).
Mechanism of action
Class III antiarrhythmic agent. Blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current. It increases the monophasic action potential duration due to delayed repolarization. The increase in the QT interval is a function of prolongation of both effective and functional refractory periods in the His-Purkinje system and the ventricles.
Therapeutic use
Used for the maintenance of normal sinus rhythm in patients with atrial fibrillation/flutter of more than 1 week duration who have been converted to normal sinus rhythm. Also used for the conversion of atrial fibrillation and atrial flutter to normal sinus rhythm.
Pregnancy and lactiation implications
There are no adequate, well-controlled studies in pregnant women. Dofetilide should be used with extreme caution in pregnant women only when the benefit to the patient unequivocally justifies the potential risk to the fetus.
Unlabeled use
Contraindications
Hypersensitivity to dofetilide or any component of the formulation. Patients with congenital or acquired long QT syndromes (avoid use if a baseline QT interval or QTc is >440 ms). Severe renal impairment (CrCl<20 mL/minute). Concomitant use with verapamil, cimetidine, hydrochlorothiazide, trimethoprim, itraconazole, ketoconazole, prochlorperazine, or megestrol. Baseline heart rate <50 beats/minute. Other drugs which prolong QT intervals (phenothiazines, cisapride, bepridil, tricyclic antidepressants, moxifloxacin; hypokalemia or hypomagnesemia; concurrent amiodarone, clarithromycin, or erythromycin).
Warnings and precautions
Proarrythmic effects may occur (torsade de pointes significantly increases with doses >500 μg twice daily). Reserve for patients who are highly symptomatic with atrial fibrillation/atrial flutter. Patients with second or third-degree heart block and/or sick sinus syndrome should not receive treatment unless a functional pacemaker is in place. Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Use with caution in severe hepatic or renal impairment. Concurrent use with other drugs known to prolong QTc interval is not recommended. Risk of hypokalemia and/or hypomagnesemia may be increased by potassium-depleting diuretics (increased risk of malignant arrhythmias).