Dofetilide

 Action Blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium currents.

 Indications Maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter [AF/AFl]) in patients with AF/AFl of > 1 wk duration who have been converted to normal sinus rhythm; conversion of AF/AFl to normal sinus rhythm. unlabeled use(s): Ventricular arrhythmias.

 Contraindications Hypersensitivity to drug; congenital or acquired long QT syndromes; baseline QT interval of QTc > 440 msec (500 msec in patients with ventricular conduction abnormalities); severe renal impairment (creatinine clearance < 20 ml/min); concurrent use of cimetidine, ketoconazole, trimethoprim (alone or in combination with sulfamethoxazole), or verapamil; concomitant use of known inhibitors of renal cation transport (eg, megestrol, prochlorperazine).

 Route/Dosage

ADULTS: PO The dose must be individualized according to calculated Ccr and QTc. Use the QT interval if the heart rate is < 60 bpm. There are no data on use if the heart rate is < 50 bpm. The usual recommended dose is 500 mcg twice daily, as modified by the dosing algorithm described in the manufacturer's prescribing information.

 Interactions

Cimetidine, inhibitors of renal cationic exchange (eg, megestrol, phenothiazines), ketoconazole, trimethoprim (alone or in combination with sulfamethoxazole), verapamil: Are contraindicated. Drugs actively secreted by renal cationic secretion (eg, amiloride, metformin, triamterene), inhibitors of CYP3A4 isozymes (eg, amiodarone, azole antifungal agents, cannabinoids, diltiazem, grapefruit juice, macrolide antibiotics, nefazodone, norfloxacin, protease inhibitors, quinine, serotonin reuptake inhibitors, zafirlukast): May increase dofetilide levels; use with caution. Class I (eg, quinidine) or Class III (eg, sotalol) antiarrhythmics: Withhold for ³ 3 half-lives prior to dosing with dofetilide. Drugs that prolong the QT interval (eg, bepridil, cisapride, phenothiazines, tricyclic antidepressants, erythromycin): Concurrent use not recommended.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Ventricular tachyarrhythmia; chest pain; torsades de pointes; AV block; bundle branch block; heart block; angioedema; bradycardia; cerebral ischemia; cerebrovascular accident; cardiac arrest; MI; syncope. CNS: Headache; dizziness; insomnia; migraine. DERM: Rash. EENT: Increased cough. GI: Diarrhea; abdominal pain. HEPA: Liver damage. RESP: Respiratory tract infection; dyspnea. OTHER: Flu syndrome; back pain; edema; facial paralysis; paralysis; paresthesia; sudden death.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children: Safety and efficacy not established. Elderly: Select dose with caution, reflecting the greater frequency of decreased renal function. Potassium levels: Should be within normal range prior to and during administration of drug. Renal impairment: Plasma concentrations of dofetilide may be increased; dosage must be adjusted based on creatinine clearance. Severe hepatic impairment: Use with caution. Torsades de pointes: Risk may be reduced by controlling plasma concentrations of dofetilide by dosing according to creatinine clearance and monitoring ECG.