Propafenone Hydrochloride - Restoring the Heart Beat

Overview

Propafenone hydrochloride is used for treating certain types of serious and possibly fatal irregular or abnormal heartbeat, including paroxysmal supraventricular tachycardia and atrial fibrillation. It is used to restore a normal heart rhythm and maintain a steady and regular heartbeat. Propafenone hydrochloride is known as an antiarrhythmic drug that works by blocking the activity of certain electrical signals in the heart, which can cause an irregular heartbeat. Propafenone hydrochloride was approved in March 2003 by the Food and Drug Administration (FDA).

Dosage

Propafenone hydrochloride comes in tablet form with 150, 225, and 300 milligrams strengths.

What Is the Clinical Use of Propafenone Hydrochloride?

Propafenone hydrochloride is used for the following reasons-

• It is used to prolong the time for recurrence of paroxysmal atrial fibrillation or flutter (PAF) associated with any disabling symptoms in patients without structural heart disease.

• It is used to prolong the time for recurrence of paroxysmal supraventricular tachycardia (PSVT) associated with any disabling symptoms in patients without structural heart disease.

• It is used to treat ventricular arrhythmias, such as sustained ventricular tachycardia.

Warnings and Precautions-

• Proarrhythmic Effects- Propafenone has proarrhythmic effects such as sudden death or life-threatening ventricular arrhythmias like ventricular tachycardia, ventricular fibrillation, asystole, and torsade de pointes. It can also worsen premature ventricular contractions or supraventricular arrhythmias and can prolong the QT interval. It is, therefore, important that each patient prescribed Propafenone hydrochloride must be evaluated electrocardiographically before and during the therapy to determine whether the response to the drug supports continued treatment. Because Propafenone can prolong the QRS interval in the electrocardiogram, and changes in the QT interval are difficult to interpret.

• Brugada Syndrome- Brugada Syndrome can be unmasked after exposure to Propafenone hydrochloride. Perform an ECG (electrocardiogram) after the initiation of Propafenone hydrochloride; ECG must be performed, and if any changes appear that are suggestive of Brugada syndrome, then the drug should be discontinued.

• Drugs That Prolong the QT Interval and Antiarrhythmic Agents- The use of Propafenone hydrochloride combined with other drugs that can prolong the QT interval has not been studied extensively. Such drugs may include many antiarrhythmics, like phenothiazines, oral macrolides, and tricyclic antidepressants. Withhold class 1A and 3 antiarrhythmic agents for at least five half-lives before initiating Propafenone hydrochloride. Avoid using Propafenone with class 1A and 3 antiarrhythmic agents. There is limited experience with the concomitant use of class 1B and 1C antiarrhythmics.

• Heart Failure- Propafenone can provoke heart failure in patients who have a history of heart failure.

• Conduction Disturbances- Propafenone hydrochloride slows atrioventricular conduction and can also cause dose-related first-degree AV block. The average PR interval prolongation and increase in QRS duration are also dose-related. Propafenone should not be given to patients with intraventricular and atrioventricular conduction defects in the absence of a pacemaker.

• Effects of Pacemaker- Propafenone hydrochloride can alter both the pacing and sensing thresholds of implanted pacemakers as well as defibrillators. During and after the therapy, the devices should be monitored and re-programmed accordingly.

• Agranulocytosis- Agranulocytosis was reported in some patients receiving Propafenone. Generally, agranulocytosis occurred within the first two months of Propafenone therapy, and after discontinuing the therapy, the white count normalized by fourteen days. Unexplained fever or decrease in the white cell count, especially in the first three months of therapy, needs consideration of possible agranulocytosis or granulocytopenia. Patients are instructed to report immediately for any signs of infection like fever, chills, or sore throat.

• Hepatic Dysfunction- Propafenone hydrochloride is highly metabolized by the liver. Hence it should be closely monitored in patients who have moderate to severe liver disease.

• Renal Dysfunction- Propafenone hydrochloride should be closely monitored in patients with impaired renal function, as 50 % of the drug is excreted through urine.

• Myasthenia Gravis- Exacerbation of myasthenia gravis has been reported while treated with Propafenone hydrochloride.

• Elevated ANA Titers- Positive ANA titers were reported in some patients receiving Propafenone. They have been reversible after the cessation of the treatment and may also disappear in some cases even after continued Propafenone therapy. Patients should be carefully evaluated who develop an abnormal ANA test, and the therapy should be discontinued if the persistent or worsening elevation of ANA titers is detected.

Drug Interactions

Drugs that inhibit CYP2D6, such as Paroxetine, Desipramine, Sertraline, or Ritonavir, and CYP3A4, such as Ketoconazole, Saquinavir, Ritonavir, or Erythromycin, are expected to cause increased plasma levels of Propafenone hydrochloride. The combination of CYP3A4 inhibition and CYP2D6 deficiency or CYP2D6 inhibition with the administration of Propafenone can increase the risk of adverse reactions, including pro-arrhythmia. Hence, the continuous use of Propafenone hydrochloride with both a CYP2D6 and a CYP3A4 inhibitor must be avoided.

Use in Specific Populations

• Pregnancy- There are no studies of Propafenone hydrochloride available in pregnant women. Any drug-associated risks of birth defects, miscarriage, or adverse maternal or fetal outcomes have not been reported yet. Untreated arrhythmias during pregnancy can pose a risk to the pregnant woman and fetus. Propafenone hydrochloride and its metabolite, 5-OH-propafenone, can cross the placenta in humans. In animal studies, Propafenone hydrochloride was not teratogenic. At maternally toxic doses ranging from two to six times the maximum recommended human dose, adverse developmental outcomes were reported while administering to pregnant rats and rabbits during organogenesis or while administering to pregnant rats in the mid-gestation period through weaning of their offspring.

• Lactation- Propafenone hydrochloride and its active metabolite, 5-OH-propafenone, are found in human milk, but the levels are likely to be low. No data is available on the effects of Propafenone hydrochloride on the breastfed infant or the effects on milk production. The developmental and health benefits of the infant must be considered, along with the mother’s clinical need for Propafenone.

• Pediatric Use- The safety and effectiveness of Propafenone hydrochloride in children have not been established yet.

• Geriatric Use- The dosage selection for an older patient should be cautious. It should be started at the low end of the dose range after considering the frequency of renal, hepatic, and cardiac function, other associated diseases, or any other drug therapy.

For Patients

What Is Arrhythmia?

Arrhythmia is the term used for an irregular or abnormal heartbeat. A person with arrhythmia may experience symptoms like a feeling of skipped heartbeat, pounding in the chest, dizziness, shortness of breath, weakness, chest discomfort, etc. There are many causes of arrhythmia, such as coronary artery disease, irritable tissue in the heart due to acquired or genetic causes, high blood pressure, cardiomyopathy (changes in the heart muscle), valve disorders, any electrolyte imbalance in the blood, including sodium or potassium imbalances, injury from a heart attack, healing process after heart surgery or any other medical conditions. Arrhythmias can be treated with medications and devices like pacemakers or defibrillators.

Why Is Propafenone Hydrochloride Prescribed?

Propafenone hydrochloride is used to treat arrhythmia (irregular heartbeat) and maintain a normal heart rate. Propafenone comes under a class of medications known as antiarrhythmics, and they work by acting on the heart muscle in order to improve the heart's rhythm.

How Propafenone Hydrochloride Should Be Used?

• Propafenone hydrochloride comes in a tablet form and an extended-release capsule which is taken by mouth.

• The tablet is usually prescribed to be taken thrice a day, once every eight hours, and the extended-release capsule is taken twice a day, once every twelve hours, with or without food.

• Patients are advised to follow the directions on the prescription label carefully and ask their doctor or pharmacist to explain any part they do not understand.

• Propafenone should be taken exactly as directed. It should not be taken more or less or more often than prescribed by the doctor. The whole capsule should be swallowed, and it should not be crushed or divided into small contents.

• The patients are advised to take Propafenone in a hospital so that the doctor can monitor them carefully as their body gets used to the medication. The doctor may start on a low dose of Propafenone and gradually increase it, not more often than once every five days.

• Propafenone may control irregular heartbeat, but it will not cure it.

• The patients are advised to continue Propafenone even if they feel well. It should not be stopped without consulting the doctor; otherwise, the heartbeat may become irregular if Propafenone is stopped suddenly.

What Special Precautions Should Be Followed?

• The doctor should be informed if the patient is allergic to Propafenone or any ingredients present in Propafenone or any other medications.

• The doctor should be informed about any prescription or nonprescription drugs that the patient is taking.

• Any herbal, dietary, or vitamin supplements taken by the patient should be informed to the doctor.

• Medications like anticoagulants, antibiotics, antihistamines, beta-blockers, antidepressants, medications for irregular heartbeat, medications for mental illness and nausea, and selective serotonin reuptake inhibitors (SSRIs) should be mentioned to the doctor.

• Inform the doctor if the patient experiences sweating, excessive diarrhea, loss of appetite, vomiting, or decreased thirst or has ever had a slow heartbeat, low blood pressure, high or low levels of sodium, potassium, chloride, or bicarbonate in the blood, asthma, heart failure, or any other condition that causes the patient’s airways to become narrow after taking Propafenone.

• If a patient has or has ever had a pacemaker, myasthenia gravis, or liver or kidney disease, then they should be informed to the doctor.

• If a patient is pregnant or breastfeeding or is planning to get pregnant, then they should inform the doctor.

• If a patient is about to undergo any surgery, including dental surgery, then the doctor should be informed about Propafenone.

• This medication can make a person feel dizzy or drowsy, so it is advisable not do any activity that requires attention, like driving a vehicle.

• The use of tobacco can decrease the effectiveness of this medication.

What to Do if a Dose Is Missed?

The missed dose must be taken as soon as the patient remembers it. However, the missed dose can be skipped if it is almost time for the next dose. The patient should never take an extra dose to compensate for the missed dose.

What Are the Side Effects of Propafenone?

• Diarrhea.

• Headache.

• Nausea.

• Vomiting.

• Dry mouth.

• Constipation.

• Loss of appetite.

• Acidity.

• Unusual taste in the mouth.

• Anxiety.

• Tiredness.

• Blurred vision.

• Uncontrollable shaking of a part of the body.

• Difficulty with coordination.

• Difficulty falling asleep or staying asleep.

• Wheezing.

• Difficulty breathing.

• Chest pain.

• Slow, fast, or pounding heartbeat.

• New or worsening irregular heartbeat.

• Sudden, unexplained weight gain.

• Swelling of the hands, feet, ankles, or lower legs.

• Skin rash.

• Fainting.

• Unexplained fever, chills, weakness, or sore throat.

Storage and Disposal-

• The medication should be kept in a tightly sealed container and stored at room temperature, away from direct sunlight.

• Unneeded medication should be disposed of in such a way that children or pets cannot consume them.

• It is advisable to contact the local garbage collecting/recycling department to dispose of the medication.

What Should Be Done in Case of an Overdose?

In case of an overdose, immediately contact the poison control helpline number. If the patient has collapsed or cannot be awakened or experiences seizures, then they should be rushed to the hospital.

Other Information

• Any other person apart from the patient for whom the medication is not prescribed should not take it.

• It is important to keep a written list of the prescription and nonprescription drugs that the patient is taking.

• The written list should be carried out while visiting a doctor or in case of emergencies.

For Doctors

Indications-

Propafenone is used to prolong the time for the recurrence of paroxysmal atrial fibrillation or flutter (PAF) associated with any disabling symptoms in patients without structural heart disease. It is also used for treating life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia.

Mechanism of Action-

The electrophysiological effect of Propafenone hydrochloride manifests itself in a reduction of the upstroke velocity of the monophasic action potential. In the Purkinje fibers, and to some lesser extent, myocardial fibers, Propafenone hydrochloride can reduce the fast inward current carried by the sodium ions, which is responsible for the antiarrhythmic action of the drug. The diastolic excitability threshold is increased, and the effective refractory period is prolonged. Propafenone hydrochloride can reduce spontaneous automaticity and depresses the triggered activity. In vitro, under very high concentrations, Propafenone hydrochloride inhibits a slow inward current carried by the calcium, although this calcium antagonist effect does not contribute to the antiarrhythmic efficacy.

Pharmacodynamics-

Propafenone hydrochloride comes under class 1C antiarrhythmic drug with local anesthetic effects, and it has a direct stabilizing action on the myocardial membranes. It is used for treating atrial and ventricular arrhythmias. Propafenone acts by inhibiting the sodium channels and restricts the sodium from entering cardiac cells, which results in reduced excitation. The drug has local anesthetic activity approximately equal to procaine.

Pharmacokinetics-

• Absorption- Propafenone is nearly completely absorbed through oral administration (90 %). The systemic bioavailability ranges from five to fifty percent.

• Volume of Distribution- 252 liters.

• Protein Binding- 97 %.

• Metabolism- Propafenone is metabolized primarily in the liver, where it is rapidly and extensively metabolized to two active metabolites, 5-hydroxy propafenone and N-dipropyl propafenone. These metabolites have antiarrhythmic activity comparable to Propafenone but are present in less than twenty-five percent concentrations than Propafenone concentrations.

• Route of Elimination- Approximately fifty percent of Propafenone metabolites are excreted in the urine after administration of immediate-release tablets.

• Half-Life- Two to ten years.

Usage Considerations-

• The use of Propafenone hydrochloride in patients with permanent atrial fibrillation or in patients with atrial flutter or PSVT has not been evaluated. Propafenone hydrochloride tablets should not be used to control ventricular rate during atrial fibrillation.

• Some patients with atrial flutter who underwent treatment with Propafenone hydrochloride have developed 1:1 conduction, producing an increased ventricular rate. Concomitant treatment with drugs that increase the functional atrioventricular nodal refractory period is recommended.

• The use of Propafenone hydrochloride in patients with chronic atrial fibrillation has not yet been evaluated.

• Due to the proarrhythmic effects of Propafenone hydrochloride, it is not recommended to be used with lesser ventricular arrhythmias, even if the patients are symptomatic. Any drug use should be reserved for patients for whom the physician feels the potential benefits can outweigh the risks.

Dosage Administration-

• The dosage of Propafenone hydrochloride tablets should be individually titrated based on the response and tolerance of the patient.

• Initiate the therapy with Propafenone hydrochloride tablets 150 milligrams, given every 8 hours (450 milligrams per day). Dosage can be increased at a minimum of three to four-day intervals to 225 milligrams every 8 hours (675 milligrams per day). If an additional therapeutic effect is needed, the dosage of Propafenone hydrochloride tablets can be increased to 300 milligrams every 8 hours (900 milligrams per day). The usefulness and safety of doses exceeding 900 milligrams per day have not yet been established.

• In hepatic impairment patients or those with a significant widening of the QRS complex or second- or third-degree AV block, a reduction in the dosage should be considered.

• With other antiarrhythmic agents, in elderly patients or in ventricular arrhythmia patients with previously marked myocardial damage, the dose of Propafenone hydrochloride should be increased gradually during the initial phase of treatment.

• The combination of cytochrome P450 3A4 inhibition and either cytochrome P450 2D6 deficiency or CYP2D6 inhibition with the simultaneous administration of Propafenone can increase the concentration of Propafenone hydrochloride and hence increase the risk of pro-arrhythmia and other adverse events. Therefore, the continuous use of Propafenone hydrochloride with both a CYP2D6 and a CYP3A4 inhibitor must be avoided.

Adverse Reactions-

• Unusual taste.

• Nausea and vomiting.

• Headache.

• Dizziness.

• Diarrhea.

• Constipation.

• Weakness.

• Fatigue.

• Blurred vision.

• Dyspnoea.

• CHF.

• Wide complex tachycardia.

• Palpitations.

• Bradycardia.

• Tremor.

• Anorexia.

• Ataxia.

Contraindications

Propafenone hydrochloride is contraindicated under the following conditions-

• Heart failure.

• Cardiogenic shock.

• Sinoatrial, intraventricular, and atrioventricular disorders of impulse generation or conduction.

• Brugada Syndrome.

• Marked hypotension.

• Bradycardia.

• Bronchospastic disorders or severe obstructive pulmonary disease.

• Marked electrolyte imbalance.