propafenone

BEERS REMS

Life-threatening ventricular arrhythmias, including ventricular tachycardia (immediate-release only).
Prolongs the time to recurrence of symptomatic paroxysmal atrial arrhythmias, including paroxysmal atrial fibrillation/flutter and paroxysmal supraventricular tachycardia.

Unlabeled Use:

Single-dose treatment for atrial fibrillation.

Action ⬆ ⬇

Slows conduction in cardiac tissue by altering transport of ions across cell membranes.

Therapeutic effects:

Suppression of ventricular arrhythmias.
Prolonged time to recurrence of symptomatic paroxysmal atrial arrhythmias, including paroxysmal atrial fibrillation/flutter and paroxysmal supraventricular tachycardia.

Pharmacokinetics ⬆ ⬇

Absorption: 3–11% absorbed following oral administration.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Extensively metabolized by the liver by the CYP1A2, CYP2D6, and CYP3A4 isoenzymes (some metabolites have antiarrhythmic activity); the CYP2D6 isoenzyme exhibits genetic polymorphism (∼7% of population may be poor metabolizers and may have significantly ↑ propafenone concentrations and an ↑ risk of adverse effects). .

Half-Life: Extensive metabolizers: 2–10 hr; Slow metabolizers: 10–32 hr.

Time/Action Profile ⬆ ⬇

(antiarrhythmic effects)

ROUTE	ONSET	PEAK	DURATION
PO	hr–days	4–5 days‡	hr

‡Chronic dosing.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Cardiogenic shock;
Conduction disorders including sick sinus syndrome and heart block (without a pacemaker);
Bradycardia;
Severe hypotension;
Bronchospastic disorders or severe COPD;
Electrolyte disturbances;
Uncontrolled HF;
Brugada syndrome.

Use Cautiously in:

Severe renal impairment (dose ↓ may be necessary);
Severe hepatic impairment (dose ↓ may be necessary);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children;
Geri: Lower doses may be necessary in older adults due to age-related in renal/hepatic/cardiovascular function, concurrent chronic illnesses and medications.

Adv. Reactions/Side Effects ⬆ ⬇

CV: conduction disturbances, angina, bradycardia, hypotension, SUPRAVENTRICULAR ARRHYTHMIAS, VENTRICULAR ARRHYTHMIAS

Derm: rash

EENT: blurred vision

GI: altered taste, constipation, nausea, vomiting, diarrhea, dry mouth

Hemat: AGRANULOCYTOSIS

MS: joint pain

Neuro: dizziness, shaking, weakness

Interactions ⬆ ⬇

Drug-drug:

Any inhibitors of the CYP1A2, CYP2D6, or CYP3A4 enzyme systems may ↑ levels, including desipramine, paroxetine, ritonavir, sertraline, ketoconazole, and erythromycin (blood level monitoring recommended); concurrent use with CYP2D6 inhibitor and CYP3A4 inhibitor should be avoided.
Quinidine is a strong inhibitor of CYP2D6 and significantly ↑ levels of propafenone; concurrent use not recommended.
Propafenone is also an inhibitor of CYP2D6 and may ↑ levels of desipramine, imipramine, haloperidol, and venlafaxine.
Significantly ↑ serum digoxin levels; blood level monitoring recommended; ↓ digoxin dose may be required.
↑levels of metoprolol and propranolol; ↓ dose may be required.
Concurrent use of local anesthetics may ↑ risk of CNS adverse reactions.
↑effects of warfarin; ↓ warfarin dose if necessary; monitor INR.
Concurrent use with amiodarone can adversely effect conduction/repolarization and should be avoided.
May ↑ risk of CNS adverse reactions with lidocaine.
May ↑ cyclosporine trough levels and risk of nephrotoxicity.
Rifampin may ↓ levels and effectiveness.
Cimetidine may ↑ levels.
Orlistat may ↓ absorption.

Grapefruit juice may ↑ levels.

Route/Dosage ⬆ ⬇

PO (Adults ): 150 mg every 8 hr; may be gradually ↑ at 3–4-day intervals as required up to 300 mg every 8–12 hr. Single dose treatment of atrial fibrillation (unlabeled use): 450 or 600 mg; Sustained release: 225 mg every 12 hr; may be gradually ↑ at a minimum of 5-day intervals as required to 325 mg every 12 hr; if further ↑ is needed, may ↑ to 425 mg every 12 hr.

Availability ⬆ ⬇

(Generic available)

Sustained-release capsules: 225 mg; 325 mg; 425 mg
Tablets: 150 mg; 225 mg; 300 mg

Assessment ⬆ ⬇

Monitor ECG or use Holter monitor prior to and periodically during therapy. May cause PR and QT prolongation.
Monitor BP and pulse periodically during therapy.
Monitor intake and output ratios and daily weight. Assess patients for signs of HF (peripheral edema, rales/crackles, dyspnea, weight gain, jugular venous distention). May require reduction or discontinuation of therapy.

Lab Test Considerations:

May cause ↑ ANA titer, which is usually asymptomatic and reversible.
- Monitor prothrombin level in patients taking warfarin; may ↑ effects of warfarin.

Toxicity and Overdose:

Signs of toxicity include hypotension, excessive drowsiness, and decreased or abnormal heart rate. Notify health care professional if these signs occur.

Implementation ⬆ ⬇

PO: Propafenone therapy should be initiated in a hospital with facilities for cardiac rhythm monitoring. Most serious proarrhythmic effects are seen in the first 2 wk of therapy.
- DNC: Swallow sustained-release capsules whole; do not open, crush, or chew.
- Previous antiarrhythmic therapy should be withdrawn 2–5 half-lives before starting propafenone.
- Dose adjustments should be at least 3–4 days apart because of the long half-life of propafenone.
- Correct pre-existing hypokalemia or hyperkalemia prior to instituting therapy.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication around the clock as directed, even if feeling better. Take missed doses as soon as remembered if within 4 hr; omit if remembered later. Gradual dosage reduction may be necessary.
May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Instruct patient to notify health care professional if fever, sore throat, chills, or unusual bleeding or bruising occurs or if chest pain, shortness of breath, diaphoresis, palpitations, or visual changes become bothersome.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Advise patient to carry identification describing disease process and medication regimen at all times.
Emphasize the importance of follow-up exams to monitor progress.

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Pronunciation ⬇

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