Propafenone

Uses

Propafenone is used for the treatment of paroxysmal atrial fibrillation/flutter (PAF), paroxysmal supraventricular tachycardia (PSVT). Propafenone is also used for the treatment of documented ventricular arrhythmias.

Propafenone is also used to associated treatment for these conditions: Atrial Fibrillation, Paroxysmal Atrial Fibrillation (PAF), Paroxysmal Supraventricular Tachycardia, Arrhythmia of ventricular origin

How Propafenone works

The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.

Dosage

Propafenone dosage

The dose of Propafenone must be individually titrated on the basis of response and tolerance. It is recommended that therapy be initiated with Propafenone 150 mg given every eight hours (450 mg/day). Dosage may be increased at a minimum of 3 to 4 day intervals to 225 mg every 8 hours (675 mg/day) and if necessary, to 300 mg every 8 hours (900 mg/day). The usefulness and safety of dosages exceeding 900 mg per day have not been established.

Side Effects

Adverse reactions associated with propafenone occur most frequently in the gastrointestinal, cardiovascular and central nervous systems. Change in taste, constipation, diarrhea, dizziness, drowsiness, dry mouth, gas, headache, light-headedness, nausea, tiredness etc. may happen. Severe allergic reactions also reported with propafenone.

Toxicity

Symptoms of propafenone overdose (usually most severe within the first 3 hours) may include convulsions (rarely), heartbeat irregularities, low blood pressure, and sleepiness.

Precaution

Hepatic Dysfunction: Propafenone is highly metabolized by the liver and should therefore, be administered cautiously to patients with impaired hepatic function. As a result, the dose of propafenone given to patients with impaired hepatic function should be approximately 20 to 30% of the dose given to patients with normal hepatic function.

Renal Dysfunction: A considerable percentage of propafenone metabolites (18.5% to 38% of the dose/48 hours) are excreted in the urine. Until further data are available, propafenone should be administered cautiously to patients with impaired renal function.

Neuromuscular Dysfunction: Exacerbation of myasthenia gravis has been reported during propafenone therapy.

Interaction

Propafenone is metabolized by CYP2D6 (major pathway) and CYP1A2 and CYP3A4. Drugs that inhibit CYP2D6 (such as desipramine, paroxetine, ritonavir, sertraline), CYP1A2 (such as amiodarone) and CYP3A4 (such as ketoconazole, ritonavir, saquinavir, erythromycin and grapefruit juice) can be expected to cause increased plasma levels of propafenone. In addition, propafenone is an inhibitor of CYP2D6. Coadministration of propafenone with drugs metabolized by CYP2D6 (such as desipramine, imipramine, haloperidol, venlafaxine) might lead to increase plasma concentrations of these drugs.

Food Interaction

• Avoid grapefruit products.
• Take with or without food. Take consistently at the same time in regard to meals.

Propafenone Drug Interaction

Moderate: apixaban, metoprolol, metoprololUnknown: aspirin, ubiquinone, rosuvastatin, omega-3 polyunsaturated fatty acids, furosemide, atorvastatin, pregabalin, esomeprazole, dabigatran, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, alprazolam, rivaroxaban, cetirizine

Propafenone Disease Interaction

Major: proarrhythmic effects, bronchospastic disorder, cardiac dysfunction, AV node dysfunctionModerate: electrolyte imbalance, (+) ANA titer, liver disease, renal dysfunction

Volume of Distribution

• 252 L

Elimination Route

Nearly completely absorbed following oral administration (90%). Systemic bioavailability ranges from 5 to 50%, due to significant first-pass metabolism. This wide range in systemic bioavailability is related to two factors: presence of food (food increases bioavailability) and dosage (bioavailability is 3.4% for a 150-mg tablet compared to 10.6% for a 300-mg tablet).

Half Life

2-10 hours

Elimination Route

Approximately 50% of propafenone metabolites are excreted in the urine following administration of immediate release tablets.

Pregnancy & Breastfeeding use

Pregnancy: Propafenone has been assigned to pregnancy category C by the FDA. There are no controlled data in human pregnancy. Limited data indicate that propafenone has been administered during the third trimester of pregnancy without adverse maternal or fetal effects. Propafenone should be given during pregnancy only when benefit outweighs risk.

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from propafenone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

Propafenone is contraindicated in the presence of uncontrolled congestive heart failure, cardiogenic shock, sinoatrial, atrioventricular and intraventricular disorders of impulse generation and/or conduction (e.g. sick sinus node syndrome, atrioventricular block) in the absence of an artificial pacemaker, bradycardia, marked hypotension, bronchospastic disorders, manifest electrolyte imbalance and known hypersensitivity to the drug.

Special Warning

Pediatric Use: The safety and effectiveness of propafenone in pediatric patients have not been established.

Geriatric Use: Clinical studies of propafenone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious.

Storage Condition

Store at 25° C. Store in a cool and dry place, protected from light. Keep out of children’s reach.

Innovators Monograph

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