Dofetilide

Dofetilide Uses, Dosage, Side Effects, Food Interaction and all others data.

Dofetilide shows Vaughan Williams Class III antiarrhythmic activity. The mechanism of action is blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current, IKr. At concentrations covering several orders of magnitude, dofetilide blocks only IKr with no relevant block of the other repolarizing potassium currents (e.g., IKs, IK1). At clinically relevant concentrations, dofetilide has no effect on sodium channels (associated with Class I effect), adrenergic alpha-receptors, or adrenergic beta-receptors.

Dofetilide is an antiarrhythmic drug with Class III (cardiac action potential duration prolonging) properties and is indicated for the maintenance of normal sinus rhythm. Dofetilide increases the monophasic action potential duration in a predictable, concentration-dependent manner, primarily due to delayed repolarization. At concentrations covering several orders of magnitude, Dofetilide blocks only IKr with no relevant block of the other repolarizing potassium currents (e.g., IKs, IK1). At clinically relevant concentrations, Dofetilide has no effect on sodium channels (associated with Class I effect), adrenergic alpha-receptors, or adrenergic beta-receptors.

Dofetilide
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Dofetilide
Availability	Prescription only
Generic	Dofetilide
Dofetilide Other Names	Dofetilida, Dofetilide, Dofetilidum
Related Drugs	propranolol, amiodarone, lidocaine, verapamil, Inderal, mexiletine
Weight	125mcg, 250mcg, 500mcg
Type	Oral capsule
Formula	C₁₉H₂₇N₃O₅S₂
Weight	Average: 441.565 Monoisotopic: 441.139212369
Protein binding	60% -70%
Groups	Approved, Investigational
Therapeutic Class	Antiarrhythmic Therapy
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Maintenance of Normal Sinus Rhythm (Delay in AF/AFL Recurrence): Dofetilide is used for the maintenance of normal sinus rhythm (delay in time to recurrence of atrial fibrillation/atrial flutter [AF/AFl]) in patients with atrial fibrillation/atrial flutter of greater than one week duration who have been converted to normal sinus rhythm. Because Dofetilide can cause life-threatening ventricular arrhythmias, it should be reserved for patients in whom atrial fibrillation/atrial flutter is highly symptomatic. In general, antiarrhythmic therapy for atrial fibrillation/atrial flutter aims to prolong the time in normal sinus rhythm. Recurrence is expected in some patients.

Conversion of Atrial Fibrillation/Flutter: Dofetilide is used for the conversion of atrial fibrillation and atrial flutter to normal sinus rhythm. Dofetilide has not been shown to be effective in patients with paroxysmal atrial fibrillation.

Dofetilide is also used to associated treatment for these conditions: Symptomatic Atrial flutter, Symptomatic, recurrent Atrial Fibrillation

How Dofetilide works

The mechanism of action of Dofetilide is a blockade of the cardiac ion channel carrying the rapid component of the delayed rectifier potassium current, IKr. This inhibition of potassium channels results in a prolongation of action potential duration and the effective refractory period of accessory pathways (both anterograde and retrograde conduction in the accessory pathway).

Dosage

Dofetilide dosage

Atrial fibrillation and atrial flutter:Initially, 500 mcg bid. Reduce maintenance dose if QT interval is prolonged after the 1st dose, discontinue if QT interval is >500 milliseconds.

Side Effects

Headache, chest pain, dizziness, resp tract infection, dyspnoea, nausea, flu syndrome, insomnia, accidental injury, diarrhoea, rash, back/abdominal pain.

Interaction

Increased plasma concentration when used with drugs secreted by renal tubular cationic transport (e.g. amiloride, metformin, triamterene). Increased risk of toxicity when used with QT prolonging agents (e.g. class I/III antiarrhythmics, bepridil, cisapride, phenothiazines, TCAs, certain fluoroquinolones and oral macrolides).

Food Interaction

Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of dofetilide.
Exercise caution with St. John's Wort. Dofetilide is partially metabolized by CYP3A4, and St. John's Wort is a CYP3A4 inducer, coadministration may reduce dofetilide serum levels.
Take with or without food.

[Minor] In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide.

Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias.

The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4.

The manufacturer recommends caution.

Dofetilide Drug Interaction

Unknown: aspirin, aspirin, aspirin, aspirin, ubiquinone, ubiquinone, apixaban, apixaban, metoprolol, metoprolol, metoprolol, metoprolol, dabigatran, dabigatran, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, rivaroxaban, rivaroxaban

Dofetilide Disease Interaction

Major: long QT interval, renal impairmentModerate: electrolyte imbalance, hepatic impairment, hypokalemia

Volume of Distribution

3 L/kg

Elimination Route

>90%

Half Life

10 hours

Pregnancy & Breastfeeding use

Category catagory C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Congenital or acquired long QT syndromes, baseline QT or QTc interval >440 millisecond (>500 millisecond in patients w/ ventricular conduction abnormalities). Severe renal impairment (CrCl <20 mL/min). Concurrent use of verapamil, cation transport system inhibitors and hydrochlorothiazide.

Acute Overdose

Symptoms: Torsade de pointes.

Management: Supportive and symptomatic treatment. Administer charcoal slurry w/in 15 min of dofetilide admin. Admin of isoproterenol infusion and IV Mg sulfate may be useful in managing torsade de pointes.