DOFETILIDE

DOFETILIDE
(do-fe-ti'lyde)
Tikosyn
Classifications: antiarrhythmic, class iii; potassium channel blocker;
Therapeutic: antiarrhythmic, class iii

Prototype: Amiodarone HCl
Pregnancy Category: C

Availability

125 mcg, 250 mcg, 500 mcg capsules

Action

Class III antiarrhythmic agent that prolongs the cardiac action potential by blocking the potassium channels and thus one or more of the potassium currents. Action results in suppression of arrhythmias dependent upon reentry of potassium ions. It also prolongs the atrial and ventricular refractory period.

Therapeutic Effect

Effectiveness indicated by correction of cardiac arrhythmias.

Uses

Symptomatic atrial fibrillation and flutter.

Contraindications

QT prolongation; ventricular arrhythmias; history of torsades de points; hypersensitivity to dofetilide; electrolyte imbalances (e.g., hypokalemia, hypomagnesemia, etc.); renal failure; pregnancy (category C); lactation.

Cautious Use

Atrioventricular block, bradycardia, CHF, concurrent administration of potassium depleting diuretics, hepatic or renal impairment; history of moderate QTc interval prolongation; moderate to severe hypertension; recent MI or unstable angina; vascular heart disease; older adults. Safety and efficacy in children <18 y are unknown.

Route & Dosage

Atrial Fibrillation/Flutter
Adult: PO Based on creatinine clearance (Clcr) and QTc interval, if QTc increases by >15% from baseline or is >500 milliseconds 2–3 h after initial dose. Decrease subsequent doses by 50%.

Renal Impairment
Clcr >60 mL/min: 500 mcg b.i.d.; 40–60 mL/min: 250 mcg b.i.d.; 20–39 mL/min: 125 mcg b.i.d.

Administration

Oral
  • Do not give dofetilide if QT/QTc interval >420 milliseconds (or >500 milliseconds with ventricular conduction abnormalities).
  • Individualize doses on creatinine clearance; QTc interval is used if HR <60 bpm.
  • Administer only with continuous ECG monitoring.
  • Do not initiate therapy until 3 mo after withdrawal of previous antiarrhythmic therapy.
  • Do not initiate therapy until 3 mo after amiodarone has been withdrawn or plasma level is <0.3 mcg/mL.
  • Store at 15°–30° C (59°–86° F); protect from moisture and humidity.

Adverse Effects (≥1%)

Body as a Whole: Flu-like syndrome, back pain. CNS: Headache, dizziness, insomnia. CV: Torsades de pointes arrhythmia, ventricular arrhythmias, AV block, chest pain. GI: Nausea, diarrhea, abdominal pain. Respiratory: Respiratory infection, dyspnea. Skin: Rash.

Interactions

Drug: Dofetilide levels increased by verapamil, cimetidine, trimethoprim, ketoconazole, prochlorperazine, megestrol; do not give with drugs known to increase the QTc interval such as bepridil, phenothiazine, tricyclic antidepressants, oral macrolides, other antiarrhythmics.

Pharmacokinetics

Absorption: >90% bioavailable. Peak: 2–3 h. Distribution: 60–70% protein bound. Metabolism: In liver. Elimination: Primarily excreted unchanged in urine. Half-Life: 10 h.

Nursing Implications

Assessment & Drug Effects

  • Monitor ECG continuously during first 3 mo of therapy; then periodically.
  • Do not discharge patient until 12 h after conversion to normal sinus rhythm.
  • Lab tests: Baseline and periodic serum electrolytes (including magnesium), periodic CBC, and routine blood chemistry. Serum potassium must be within normal limits prior to and throughout therapy with dofetilide.
  • Notify physician immediately of electrolyte imbalances, especially hypokalemia and hypomagnesemia.

Patient & Family Education


Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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