Dofetilide

Indications

Dofetilide is used for: Conversion of Atrial Fibrillation/Flutter to Normal Sinus Rhythm

Adult Dose

Conversion of Atrial Fibrillation/Flutter to Normal Sinus Rhythm QTc must be <440 msec (or <500 msec with ventricular conduction abnormalities) before initiating first dose; contraindicated if >440 msec (or >500 msec with ventricular conduction abnormalities) Initial dose CrCl >60 mL/min: 500 mcg PO q12hr CrCl 40-60 mL/min: 250 mcg PO q12hr CrCl 20-40 mL/min: 125 mcg PO q12hr CrCl <20 mL/min: Contraindicated Sinus Rhythm Maintenance After Conversion Post initial dose adjustment based on QTc (2-3 hours after initial dose) If QTc increases <15% of baseline, continue current dose If QTc increases >15% or >500 msec (550 msec with ventricular conduction abnormalities) decrease dose as follows: If initial dose 500 mcg q12hr, decrease to 250 mcg q12hr If initial dose 250 mcg q12hr, decrease to 125 mcg q12hr If initial dose 125 mcg q12hr, decrease to 125 mcg qDay

Child Dose

Renal Dose

Administration

Contra Indications

Hypersensitivity Congenital or acquired long QT syndromes; do not use with baseline QTc >440 msec (500 msec with ventricular conduction abnormalities) Concomitant use of cation transport system inhibitors (eg, verapamil, cimetidine, trimethoprim, ketoconazole, prochlorperazine, dolutegravir and megestrol); each of these drugs cause a substantial increase in dofetilide plasma concentrations Severe renal impairment: CrCl <20 mL/min

Precautions

Atrioventricular block, bradycardia, electrolyte imbalance, patients taking potassium-depleting diuretics, moderate QT interval prolongation prior to treatment, proarrhythmic events, liver disease, renal impairment Coadministration of drugs that prolong QT interval and other antiarrhythmic agents: phenothiazines, cisapride, bepridil, TCAs, oral macrolides, class I or class III antiarrhythmics & amiodarone Grapefruit juice may increase levels; avoid concurrent use Magnesium and potassium serum levels should be maintained within normal range to avoid QTc prolongation Monitoring Baseline & continuous ECG during therapy Do not initiate if baseline QTc >440 msec (500 msec in patients w/ ventricular conduction problems) Do not initiate if heart rate <60 bpm Baseline CrCl determines initial dosage; dosage adjustments determined by QTc changes Reevaluate renal function and QTc q3mth or more often if medically required

Pregnancy-Lactation

Pregnancy Category: C Lactation: excretion in milk unknown/not recommended

Interactions

Adverse Effects

Side effects of Dofetilide : >10% Headache (11%) 1-10% Chest pain (10%) Dizziness (8%) Insomnia (4%) Respiratory tract infection (7%) Dyspnea (6%) Rash (3%) Flu-like syndrome (4%) Back pain (3%) Ventricular tachycardia (3-4%) Torsade de pointes (3% in HF patients and 0.9% in patients with recent MI) Nausea (5%) Diarrhea (3%) Frequency Not Defined AV block, QTc interval prolongation, torsades de pointes, ventricular arrhythmias Difficulty sleeping Liver damage Cough Paresthesia Angioedema

Mechanism of Action

Blocks channels carrying delayed rectifier potassium currents, IKr Markedly prolongs action potential as a result of delayed repolarization