Class III antiarrhythmic, selective IKr blocker
Brand names: Tikosyn
Updated · Methodology
Second line
Dofetilide is a second-line antiarrhythmic for sinus rhythm maintenance in atrial fibrillation when amiodarone failed or is contraindicated. 2024 supports use in patients without heart failure. REMS requires inpatient initiation with continuous ECG monitoring for the first 3 days.
Sources
ICD-10: I48 · ICD-11: BC81.3
Selectively blocks IKr potassium channels, prolonging repolarisation and effective refractory period in atria and ventricles. Renally excreted with minimal metabolism. REMS – inpatient initiation only with QTc and creatinine titration.
Limited data. Use only if benefit outweighs risk.
Milk excretion data lacking. Breastfeeding not recommended.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
4 pairs found. Sorted from critical to minor.
Mechanism
Hydrochlorothiazide causes hypokalaemia and hypomagnesaemia; combined with dofetilide leads to torsades de pointes. Tikosyn Section 4.3 strict contraindication.
Symptoms
Torsades de pointes, syncope, cardiac arrest.
Management
Combination contraindicated. Use loop diuretic with potassium monitoring.
Sources
Mechanism
Ketoconazole inhibits CYP3A4 (dofetilide metabolism) and OCT2. Dofetilide rises 4-fold. Tikosyn Section 4.3.
Symptoms
Torsades de pointes.
Management
Combination contraindicated.
Mechanism
Trimethoprim inhibits renal OCT2 transporter clearing dofetilide. Levels double. Tikosyn Section 4.3 strict contraindication.
Symptoms
Torsades de pointes.
Management
Combination contraindicated.
Mechanism
Verapamil inhibits renal OCT2 transporter that clears dofetilide. Dofetilide doubles, QT prolongs. Tikosyn Section 4.3 strict contraindication.
Symptoms
Torsades de pointes within hours.
Management
Combination contraindicated.
Sources
Verbatim lines from the interaction sections, in the language of the label
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug-Drug Interactions: Cimetidine: (see WARNINGS, CONTRAINDICATIONS ) Concomitant use of cimetidine is contraindicated. Cimetidine at 400 mg BID (the usual prescription dose) co-administered with…»FDA, section 7 · Open on DailyMed
«Drug Interactions: Coadministration of a number of CYP3A4 substrates such as dofetilide, quinidine cisapride and pimozide is contraindicated with ketoconazole tablets. Coadministration with…»FDA, section 4 · Open on DailyMed
«Fármacos que prolongan el intérvalo QT, p.ej., mizolastina, pimozida, quinidina, sertindol, terfenadina, astemizol, cisaprida, bepridil, dofetilida, halofantrina, ya que el incremento de las…»AEMPS, section 4.3 · Open on CIMA
«DRUG INTERACTIONS: Because pimozide prolongs the QT interval of the electrocardiogram, an additive effect on QT interval would be anticipated if administered with other drugs, such as phenothiazines…»FDA, section 7 · Open on DailyMed
«Administración concomitante de antiarrítmicos de clase Ia (p.ej. quinidina) o clase III (p.ej. dofetilida, sotalol) distintos de la amiodarona.»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: dofetilide, sotalol, quinidine, other Class Ia and III anti-arrhythmics, mesoridazine, thioridazine, chlorpromazine, droperidol, pimozide, sparfloxacin, gatifloxacin, moxifloxacin…»FDA, section 4 · Open on DailyMed
«DRUG INTERACTIONS: Disopyramide Quinidine Dofetilide Amiodarone Sotalol Procainamide Not Recommended Disopyramide, Quinidine: There have been postmarketing reports of torsades de pointes occurring…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Lamotrigine is an inhibitor of renal tubular secretion via organic cationic transporter 2 (OCT2) proteins [see Clinical Pharmacology (12.3) ] . This may result in increased plasma…»FDA, section 7 · Open on DailyMed
«Uso con medicamentos que prolongan el intervalo QT: Debido a que el tratamiento de deprivación de andrógenos puede prolongar el intervalo QT, se recomienda precaución cuando se administre abiraterona…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos asociados con prolongación del intervalo QT: Azitromicina se debe usar con precaución en pacientes que reciben medicamentos que se sabe que prolongan el intervalo QT (ver sección 4.4)…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos afectados por alteraciones de los niveles de potasio: Antiarrítmicos clase III (p.ej., amiodarona, sotalol, dofetilida, ibutilida)»AEMPS, section 4.5 · Open on CIMA
«Medicamentos que ocasionan “torsades de pointes”, pero sin limitarse a: - antiarrítmicos del grupo III (ej. amiodarona, sotalol, dofetilida, ibutilida, bretilio),»AEMPS, section 4.5 · Open on CIMA
«Se debe valorar cuidadosamente el uso concomitante de Eftoran con medicamentos que prolongan el intervalo QT o medicamentos capaces de inducir Torsade des Pointes, tales como antiarrítmicos de clase…»AEMPS, section 4.5 · Open on CIMA
«Potentially Significant Pharmacodynamic Drug Interactions: Antiarrhythmics Dofetilide Concomitant administration with digoxin was associated with a higher rate of torsades de pointes.»FDA, section 7 · Open on DailyMed
«Está contraindicado el uso concomitante de las siguientes sustancias: antiarrítmicos de clase III (p. ej., amiodarona, dofetilida, dronedarona, ibutilida, sotalol)»AEMPS, section 4.5 · Open on CIMA
«Efectos cardiovasculares: Antiarrítmicos de clase III (p. ej., amiodarona, dofetilida, dronedarona, ibutilida, sotalol).»AEMPS, section 4.5 · Open on CIMA
«Antivirales para uso sistémico: Dofetilida»AEMPS, section 4.3 · Open on CIMA
«Interacciones con otros medicamentos: antiarrítmicos de la clase clase III (p. ej., amiodarona, sotalol, dofetilida, ibutilida),»AEMPS, section 4.5 · Open on CIMA
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Dofetilide is evaluated for the following indications with varying evidence strength: Atrial fibrillation (evidence tier B). See the full indication matrix with dosing and citations above on this page.
Common side effects of Dofetilide (≥ 1 in 100): Headache, Chest pain, Dizziness, Insomnia. See the Safety section for uncommon and serious reactions.
Limited data. Use only if benefit outweighs risk.
Milk excretion data lacking. Breastfeeding not recommended.
Dofetilide is contraindicated in: Baseline QTc above 440 ms; Creatinine clearance below 20 mL/min; Combination with verapamil, ketoconazole, cimetidine, trimethoprim, prochlorperazine, megestrol, hydrochlorothiazide (FDA REMS); Congenital long QT syndrome. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Dronedarone, Flecainide, Hawthorn (Crataegus monogyna / laevigata), Isosorbide dinitrate, Ivabradine, Propafenone, Amiodarone, Isosorbide mononitrate