What are the contraindications for Dofetilide (antiarrhythmic medication) in atrial fibrillation (afib) treatment?

Contraindications for Dofetilide in Atrial Fibrillation Treatment

Dofetilide is absolutely contraindicated in patients with congenital or acquired long QT syndromes, baseline QT interval or QTc >440 msec (500 msec in patients with ventricular conduction abnormalities), and severe renal impairment (creatinine clearance <20 mL/min). 1

Absolute Contraindications

• Prolonged QT interval: Baseline QT interval or QTc >440 msec (500 msec in patients with ventricular conduction abnormalities) 2, 1
• Severe renal disease: Creatinine clearance <20 mL/min 1
• Congenital or acquired long QT syndromes 1
• Hypokalemia or hypomagnesemia: Must be corrected before initiating dofetilide 2, 1
• Concomitant use of specific medications that inhibit renal cation transport system:
  • Verapamil 1
  • Cimetidine 1
  • Trimethoprim (alone or with sulfamethoxazole) 1
  • Ketoconazole 1
  • Prochlorperazine 1
  • Dolutegravir 1
  • Megestrol 1
• Concomitant use of hydrochlorothiazide (alone or in combinations with triamterene) 1
• Known hypersensitivity to dofetilide 1

Medication Interactions Requiring Caution

• Other QT-prolonging drugs: Phenothiazines, cisapride, bepridil, tricyclic antidepressants, certain oral macrolides, and certain fluoroquinolones 1
• Class I or Class III antiarrhythmic agents: Should be withheld for at least three half-lives prior to dosing with dofetilide 1
• Amiodarone: Dofetilide should only be administered if serum amiodarone levels are below 0.3 mg/L or amiodarone has been withdrawn for at least three months 1
• Diuretic therapy: Potassium-depleting diuretics increase the risk of torsades de pointes 2, 1

Clinical Conditions Requiring Careful Consideration

• Heart failure: While dofetilide can be used in heart failure patients, careful monitoring is required due to increased risk of torsades de pointes 2
• Post-myocardial infarction: Benefit must be weighed against risk, though DIAMOND-MI trial showed potential benefit in selected post-MI patients 2
• Renal dysfunction: Dose must be adjusted based on creatinine clearance 1, 3

Risk of Torsades de Pointes

• Incidence: 0.8% overall in patients with supraventricular arrhythmias 1
• Timing: Majority of torsades de pointes episodes occur within the first three days of therapy 1, 3
• Dose-dependent risk: Higher doses associated with increased risk (up to 10.5% at >500 mcg BID) 1, 4

Required Monitoring and Precautions

• Mandatory hospitalization: Patients must be hospitalized for a minimum of 3 days when initiating or reinitiating dofetilide 3
• Continuous ECG monitoring: Required during initial dosing period 3
• Renal function assessment: Must be performed before starting therapy and dose adjusted accordingly 1, 3
• Electrolyte monitoring: Potassium and magnesium levels must be within normal range before and during administration 1
• QT interval monitoring: Regular assessment required with dose adjustments based on QT response 1, 3

Common Pitfalls to Avoid

• Failure to adjust dose based on renal function: This significantly increases the risk of torsades de pointes 1, 3
• Inadequate monitoring: Not providing continuous ECG monitoring during the initial 3-day period 3
• Concomitant medication oversights: Not thoroughly reviewing all medications for potential interactions 1
• Outpatient initiation: Dofetilide should never be initiated outside of a hospital setting 2, 3
• Electrolyte imbalances: Not correcting hypokalemia or hypomagnesemia before starting therapy 1

Dofetilide remains an effective option for conversion and maintenance of sinus rhythm in atrial fibrillation when used with strict adherence to dosing criteria and contraindications 4, 5. The risk-benefit profile is favorable when appropriate patient selection and monitoring protocols are followed 6.