doe-FET-il-ide

Therapeutic Classification: antiarrhythmics (class III)

• Maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter [AF/AFL]) in patients with AF/AFL lasting more than 1 wk and who have been converted to normal sinus rhythm.
• Conversion of AF and AFL to normal sinus rhythm.

• Blocks cardiac ion channels responsible for transport of potassium.
• Increases monophasic action potential duration.
• Increases effective refractory period.

• Prevention of recurrent AF/AFL.
• Conversion of AF/AFL to normal sinus rhythm.

Absorption: Well absorbed (>90%) following oral administration.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme; 80% excreted by kidneys via cationic renal secretion, mostly as unchanged drug; 20% excreted as inactive metabolites.

Half-life: 10 hr.

(plasma concentrations)

†Steady state levels are achieved after 2–3 days.

Contraindicated in:

• Hypersensitivity
• Congenital or acquired prolonged QT syndromes
• Baseline QTc interval >440 msec (500 msec in patients with ventricular conduction abnormalities)
• CCr <20 mL/min
• Concurrent use of verapamil, cimetidine, dolutegravir, ketoconazole, itraconazole, trimethoprim, megestrol, prochlorperazine, hydrochlorothiazide, or other QT-interval prolonging drugs
• Lactation: Lactation.

Use Cautiously in:

• Underlying electrolyte abnormalities (↑ risk of serious arrhythmias; correct prior to administration)
• CCr 20–60 mL/min (dose ↓ recommended)
• Severe hepatic impairment
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Safety and effectiveness not established in children.

CV: chest pain, QT interval prolongation, TORSADES DE POINTES.

Neuro: dizziness, headache.

Drug-Drug:

• Hydrochlorothiazide, verapamil, cimetidine, ketoconazole, itraconazole, trimethoprim, megestrol, dolutegravir, and prochlorperazine↑ levels and the risk of QT interval prolongation with arrhythmias; concurrent use contraindicated.
• QT interval prolonging drugs may ↑ the risk of QT interval prolongation with arrhythmias; concurrent use contraindicated.
• Amiloride, metformin, and triamterene may ↑ levels; use with caution.
• CYP3A4 inhibitors, including macrolides, azole antifungals, protease inhibitors, amiodarone, diltiazem, and nefazodone, may ↑ levels and the risk of arrhythmias; concurrent use should be undertaken with caution.
• Should not be used concurrently with other class I or III antiarrhythmics due to ↑ risk of arrhythmias.
• Hypokalemia or hypomagnesemia from potassium-depleting diuretics↑ the risk of arrhythmias; correct abnormalities prior to administration.
• Concurrent use of digoxin may ↑ the risk of arrhythmias.

Drug-Food:

• Grapefruit juice may ↑ levels; avoid concurrent use.

• PO (Adults): Starting dose: 500 mcg twice daily; maintenance dose: 250 mcg twice daily (not to exceed 500 mcg twice daily).

(Generic available)

• Capsules: 125 mcg; 250 mcg; 500 mcg;

• Monitor ECG, pulse, and BP continuously during initiation of therapy and for at least 3 days or a minimum of 12 hr after electrical or pharmacological conversion to normal sinus rhythm, whichever is greater, and then periodically during therapy. Evaluate QTc interval (or QT interval if heart rate <60 bpm) before starting therapy and every 3 mo during therapy. If QTc interval exceeds 440 msec (500 msec in patients with ventricular conduction abnormalities), discontinue dofetilide and monitor patient until QTc interval returns to baseline.
• Within 2–3 hr after first dose, evaluate QTc interval (or QT interval if heart rate <60 bpm). If QTc or QT interval ↑ by >15% compared to baseline or if QTc or QT interval >500 msec (550 msec in patients with ventricular conduction abnormalities), adjust doses as follows: if initial dose was 500 mcg twice daily, change to 250 mcg twice daily; if initial dose was 250 mcg twice daily, change to 125 mcg twice daily; if initial dose was 125 mcg twice daily, change to 125 mcg once a day. Determine QTc or QT interval within 2–3 hr after each subsequent dose for hospital doses 2–5. No further down titration of dose is recommended. Discontinue dofetilide if at any time after second dose is given QTc or QT interval >500 msec (550 msec in patients with ventricular conduction abnormalities).
• Assess the patient’s medication history including OTC, Rx, and natural/herbal products, with emphasis on those that interact with dofetilide (see Interactions).

• Calculate CCr prior to administration to determine dose and every 3 mo during therapy.
  • Correct hypokalemia before starting therapy. Maintain serum potassium in normal range during dofetilide therapy.

• Dofetilide must be initiated or reinitiated and monitored for at least 3 days in a setting that provides continuous ECG monitoring and has personnel trained in the management of serious ventricular arrhythmias. Due to the potential for life-threatening ventricular arrhythmias, dofetilide is usually used for patients with highly symptomatic AF/AFL.
  • Patients with AF should be anticoagulated according to usual protocol prior to electrical or pharmacological cardioversion.
  • Make sure patient has an adequate supply of dofetilide prior to discharge to prevent interruption of therapy.
  • Patients should not be discharged from the hospital within 12 hr of electrical or pharmacological conversion to normal sinus rhythm.
• PO: Administer at the same time each day without regard to food.

• Instruct patient to take medication as directed, even if feeling well. If a dose is missed, skip dose; do not double next dose. Take next dose at usual time.
• Advise patient to avoid grapefruit juice during therapy; may increase drug levels.
• Advise patient to read Medication Guide prior to starting therapy and each Rx refill in case of changes. Emphasize need for adherence with therapy, potential for drug interactions, and need for periodic monitoring to minimize the risk of serious arrhythmias.
• Instruct patient or family member on how to take pulse. Advise patient to report changes in pulse rate or rhythm to health care professional.
• May cause dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
• Advise patient to consult health care professional immediately if they faint, become dizzy, or have fast heartbeat. If health care professional is unavailable, instruct patient to go to nearest hospital emergency department, take remaining dofetilide capsules to hospital, and show them to health care professional. If symptoms associated with altered electrolyte balance such as excessive or prolonged diarrhea, sweating, or vomiting or loss of appetite or thirst occur, notify health care professional immediately.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Emphasize the importance of routine follow-up exams to monitor progress.

• Prevention of recurrent AF/AFL.
• Conversion of AF/AFL to normal sinus rhythm.
  • If patients do not convert to normal sinus rhythm within 24 hr of initiation of therapy, electrical conversion should be considered.

Tikosyn