Usage
Propafenone is prescribed for the treatment of life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia, and symptomatic atrial fibrillation/flutter in patients without structural heart disease. Its pharmacological classification is antiarrhythmic, specifically Class IC. Propafenone works primarily by blocking sodium channels in the heart, slowing the conduction of electrical impulses, and stabilizing the heart rhythm. It also exhibits some beta-blocker and potassium channel blocking activity.
Alternate Names
The generic name is propafenone hydrochloride. A common brand name is Rythmol (including Rythmol SR for the extended-release formulation).
How It Works
Pharmacodynamics: Propafenone reduces the upstroke velocity of the cardiac action potential (Phase 0), prolongs myocardial refractoriness, and slows conduction velocity, particularly in the atria, ventricles, and His-Purkinje system. It also has weak beta-blocking effects, reducing heart rate and contractility, and mild potassium channel blocking activity, further prolonging repolarization.
Pharmacokinetics:
- Absorption: Propafenone is well-absorbed orally. The extended-release formulation (Rythmol SR) provides slower and more sustained absorption. Food may enhance bioavailability.
- Metabolism: Propafenone is extensively metabolized in the liver, primarily by CYP2D6, CYP3A4, and CYP1A2 enzymes, to active and inactive metabolites. Genetic polymorphisms in CYP2D6 influence individual responses and may lead to significant variability in plasma concentrations.
- Elimination: Propafenone and its metabolites are excreted mainly in urine and to some extent in feces. The elimination half-life varies, with longer half-lives observed in patients with hepatic impairment and in slow CYP2D6 metabolizers.
Dosage
Standard Dosage
Adults:
- Immediate-Release (IR) Tablets: Initial dose: 150 mg every 8 hours. The dose may be increased at 3-4 day intervals to 225 mg every 8 hours, and if necessary, up to a maximum of 300 mg every 8 hours.
- Extended-Release (ER) Capsules: Initial dose: 225 mg every 12 hours. The dose may be increased at 5-day intervals to 325 mg every 12 hours and, if necessary, up to 425 mg every 12 hours.
Children:
Safety and efficacy not established in children younger than 18 years.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate cautiously due to potential age-related decrease in hepatic and renal function.
- Patients with Renal Impairment: Use with caution; dose adjustment may be needed.
- Patients with Hepatic Dysfunction: Significant dose reductions are necessary. Start with a very low dose (e.g., 150 mg once daily for mild to moderate impairment) and titrate cautiously.
- Patients with Comorbid Conditions: Careful consideration and dose adjustment may be required for patients with conditions such as congestive heart failure, bradycardia, hypotension, or bronchospastic disorders.
Clinical Use Cases
Propafenone’s use in settings such as intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations should be guided by specialist consultation and ECG monitoring. Dosage adjustments in these contexts must consider hemodynamic stability, concomitant medications, and the patient’s specific clinical condition. There are no specific dosage recommendations for these scenarios that can be provided in this general guide.
Dosage Adjustments
Dosage modifications should be made based on patient response, tolerance, ECG findings (QRS widening, PR prolongation), and the presence of renal or hepatic dysfunction. Genotyping for CYP2D6 polymorphisms can be helpful for personalized dosing.
Side Effects
Common Side Effects:
Dizziness, nausea, vomiting, unusual taste, constipation, headache, fatigue.
Rare but Serious Side Effects:
New or worsened arrhythmias (proarrhythmia), heart failure exacerbation, bronchospasm, agranulocytosis (low white blood cell count), liver dysfunction.
Long-Term Effects:
Chronic effects from prolonged propafenone use are not well-characterized but may include continued risk of proarrhythmia and potential hepatic or hematological effects.
Adverse Drug Reactions (ADR):
Significant ADRs include torsades de pointes, bradycardia, heart block, and severe hypotension, which require immediate intervention.
Contraindications
- Bradycardia, severe hypotension, sick sinus syndrome (without a pacemaker), second-degree or higher AV block (without a pacemaker), cardiogenic shock, uncontrolled heart failure, Brugada syndrome.
- Bronchospastic disorders, severe obstructive pulmonary disease.
- Hypersensitivity to propafenone.
- Concomitant use with dofetilide or other drugs that significantly prolong the QT interval.
Drug Interactions
Propafenone interacts with numerous medications, including:
- CYP2D6 and CYP3A4 inhibitors: These can increase propafenone levels, leading to toxicity. Examples include ketoconazole, ritonavir, fluoxetine, paroxetine.
- Digoxin: Propafenone increases digoxin levels.
- Warfarin: Propafenone may enhance the anticoagulant effect of warfarin.
- Beta-blockers: Additive bradycardia and hypotension may occur.
- Local anesthetics (e.g., lidocaine): Increased risk of lidocaine toxicity.
- Other antiarrhythmics (e.g., amiodarone, dofetilide): Increased risk of proarrhythmia.
Pregnancy and Breastfeeding
- Pregnancy: Propafenone crosses the placenta. Use only if the potential benefit outweighs the potential risk to the fetus. Considered relatively safe during pregnancy, but there are limited data.
- Breastfeeding: Propafenone is present in breast milk. Use with caution while breastfeeding, particularly in newborns and premature infants.
Drug Profile Summary
- Mechanism of Action: Sodium channel blocker (Class IC), weak beta-blocker, mild potassium channel blocker.
- Side Effects: Dizziness, nausea, unusual taste, proarrhythmia, heart failure exacerbation.
- Contraindications: Bradycardia, heart block, heart failure, bronchospastic disorders.
- Drug Interactions: CYP2D6 inhibitors, digoxin, warfarin, beta-blockers.
- Pregnancy & Breastfeeding: Use with caution; weigh benefits against risks.
- Dosage: IR: 150-300 mg every 8 hrs; ER: 225-425 mg every 12 hrs.
- Monitoring Parameters: ECG (QRS, PR, QT intervals), heart rate, blood pressure, liver function tests, complete blood count.
Popular Combinations
Propafenone may be combined with beta-blockers (with caution) or non-dihydropyridine calcium channel blockers for certain arrhythmias like atrial fibrillation. However, the combination should be initiated and monitored carefully due to the potential for additive bradycardia and hypotension.
Precautions
- General Precautions: Monitor ECG, heart rate, and blood pressure. Baseline and periodic liver function tests and complete blood counts are recommended. Assess for history of hypersensitivity, liver disease, or renal impairment.
- Specific Populations: As outlined above.
- Lifestyle Considerations: Alcohol may potentiate the hypotensive effects. Advise patients about potential driving impairment due to dizziness or blurred vision.
FAQs
Q1: What is the recommended dosage for Propafenone?
A: See the detailed dosage section above for specifics, including IR vs. ER formulations, adjustments for various conditions, etc.
Q2: What is the primary mechanism of action of Propafenone?
A: Propafenone primarily blocks sodium channels in the heart, slowing conduction and stabilizing rhythm.
Q3: What are the most serious side effects of Propafenone?
A: Proarrhythmia (new or worsened arrhythmias), including torsades de pointes, heart failure exacerbation, bradycardia, and heart block.
Q4: When is Propafenone contraindicated?
A: In patients with bradycardia, heart block, heart failure, bronchospastic disorders, Brugada syndrome, and hypersensitivity to propafenone.
Q5: What are important drug interactions with Propafenone?
A: Drugs metabolized by CYP2D6 and CYP3A4, digoxin, warfarin, beta-blockers, and other antiarrhythmics.
Q6: Can Propafenone be used during pregnancy and breastfeeding?
A: Use with caution in both situations. It can cross the placenta and is excreted in breast milk. Weigh benefits against risks.
Q7: How should Propafenone dosage be adjusted for patients with liver disease?
A: Significantly reduce the dose and titrate cautiously. Close monitoring is essential.
Q8: What are the monitoring parameters for patients taking Propafenone?
A: ECG, heart rate, blood pressure, liver function tests, and complete blood count.
Q9: What patient education should be provided regarding Propafenone?
A: Explain potential side effects, including dizziness and the need to avoid driving if impaired. Emphasize adherence to the prescribed dosage and regular follow-up appointments for monitoring. Advise against concomitant use of non-prescription drugs without consulting their physician.
Q10: What is the difference between Rythmol and Rythmol SR?
A: Rythmol is the immediate-release formulation of propafenone, while Rythmol SR is the extended-release version, providing more sustained drug levels.
