Drug information of Propafenone


Propafenone

Drug group:

Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes.

Mechanism of effect

Propafenone can inhibit the slow inward current carried by calcium, but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy. Moreover, Propafenone inhibits a variety of cardiac potassium currents.

Pharmacodynamic

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.
Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity.

Pharmacokinetics

Propafenone HCl is nearly completely absorbed after oral administration with peak plasma levels occurring approximately 3.5 hours after administration in most individuals. Propafenone exhibits extensive saturable presystemic biotransformation (first pass effect).
the drug is rapidly and extensively metabolized with an elimination half-life from 2 to 10 hours. Eliminated principally in feces via biliary excretion as metabolites and in urine or feces as unchanged drug (<1%).

Drug indications

Ventricular Arrhythmia

Dosage

Usual Adult Dose for Atrial Fibrillation
Initial dose :
Immediate release : 150 mg orally every 8 hours.
Extended release: 225 mg every 12 hours.
Maintenance dose :
Immediate release : May be increased at a minimum of 3 to 4 day intervals to 225 mg every 8 hours and, if necessary, to 300 mg every 8 hours.
Extended release: May be increased after 5 days of therapy to 325 mg every 12 hours. Doses up to 425 mg every 12 hours are necessary for some patients.
Usual Adult Dose for Atrial Flutter
Initial dose :
Immediate release: 150 mg orally every 8 hours.
Extended release: 225 mg every 12 hours.
Maintenance dose :
Immediate release: May be increased at a minimum of 3 to 4 day intervals to 225 mg every 8 hours and, if necessary, to 300 mg every 8 hours.
Extended release: May be increased after 5 days of therapy to 325 mg every 12 hours. Doses up to 425 mg every 12 hours are necessary for some patients.
Usual Adult Dose for Ventricular Tachycardia
Initial dose :
Immediate release: 150 mg orally every 8 hours.
Extended release: 225 mg every 12 hours.
Maintenance dose :
Immediate release: May be increased at a minimum of 3 to 4 day intervals to 225 mg every 8 hours and, if necessary, to 300 mg every 8 hours.
Extended release: May be increased after 5 days of therapy to 325 mg every 12 hours. Doses up to 425 mg every 12 hours are necessary for some patients.
Usual Adult Dose for Wolff-Parkinson-White Syndrome
Initial dose :
Immediate release: 150 mg orally every 8 hours.
Extended release: 225 mg every 12 hours.
Maintenance dose :
Immediate release: May be increased at a minimum of 3 to 4 day intervals to 225 mg every 8 hours and, if necessary, to 300 mg every 8 hours.
Extended release: May be increased after 5 days of therapy to 325 mg every 12 hours. Doses up to 425 mg every 12 hours are necessary for some patients.

Alerts

Propafenone has caused new or worsened arrhythmias. Such proarrhythmic effects include sudden death and life-threatening ventricular arrhythmias such as ventricular fibrillation, ventricular tachycardia, asystole and torsade de pointes.
• It may also worsen premature ventricular contractions or supraventricular arrhythmias, and it may prolong the QT interval. It is therefore essential that each patient given Propafenone hydrochloride tablets be evaluated electrocardiographically prior to and during therapy to determine whether the response to Propafenone hydrochloride tablets supports continued treatment.
• Because Propafenone prolongs the QRS interval in the electrocardiogram, changes in the QT interval are difficult to interpret.
• Brugada Syndrome may be unmasked after exposure to Propafenone hydrochloride . Perform an ECG after initiation of Propafenone hydrochloride, and discontinue the drug if changes are suggestive of Brugada Syndrome.
• The use of Propafenone hydrochloride tablets in conjunction with other drugs that prolong the QT interval has not been extensively studied. Such drugs may include many antiarrhythmics, some phenothiazines, tricyclic antidepressants, and oral macrolides. Withhold Class IA and III antiarrhythmic agents for at least 5 half-lives prior to dosing with Propafenone hydrochloride tablets. Avoid the use of Propafenone with Class IA and III antiarrhythmic agents (including quinidine and amiodarone).
Propafenone is metabolized by CYP2D6, CYP3A4, and CYP1A2 isoenzymes. Approximately 6% of Caucasians in the U.S. population are naturally deficient in CYP2D6 activity and to a somewhat lesser extent in other demographic groups. Drugs that inhibit these CYP pathways (such as desipramine, paroxetine, ritonavir, sertraline for CYP2D6; ketoconazole, erythromycin, saquinavir, and grapefruit juice for CYP3A4; and amiodarone and tobacco smoke for CYP1A2) can be expected to cause increased plasma levels of Propafenone.
• Propafenone exerts a negative inotropic activity on the myocardium as well as beta blockade effects and may provoke overt heart failure.
Propafenone slows atrioventricular conduction and may also cause dose-related first degree AV block. Average PR interval prolongation and increases in QRS duration are also dose-related. Do not give Propafenone to patients with atrioventricular and intraventricular conduction defects in the absence of a pacemaker .
• Propafenone may alter both pacing and sensing thresholds of implanted pacemakers and defibrillators. During and after therapy, monitor and re-program these devices accordingly.
• Agranulocytosis has been reported in patients receiving Propafenone. Generally, the agranulocytosis occurred within the first 2 months of Propafenone therapy and upon discontinuation of therapy, the white count usually normalized by 14 days.
Propafenone is highly metabolized by the liver. Severe liver dysfunction increases the bioavailability of Propafenone to approximately 70% compared to 3 to 40% in patients with normal liver function.
• Approximately 50% of Propafenone metabolites are excreted in the urine following administration of Propafenone hydrochloride.
• In patients with impaired renal function, monitor for signs of overdosage.
• Exacerbation of myasthenia gravis has been reported during Propafenone therapy.

Points of recommendation

To make sure this medicine is safe for you, tell your doctor if you have :
• If you have an allergy to propafenone or any other part of this medicine (propafenone tablets).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Breathing or lung problems, Brugada syndrome, electrolyte problems in your blood, low blood pressure, recent heart attack, sick sinus syndrome or heart block without a working pacemaker, slow heartbeat, or heart failure.
• If you have been taking any drugs to treat a heartbeat that is not normal.
• If you are breast-feeding or plan to breast-feed.
Myasthenia gravis that has gotten worse has happened during care with this medicine. Talk with the doctor.
If you have a pacemaker, talk with your doctor.
This medicine has caused new or worsened abnormal heartbeats. These can be life-threatening or can cause sudden death. Talk with the doctor.
You will need an ECG before starting this medicine ( propafenone tablets ) and during treatment. Talk with your doctor.
Avoid grapefruit and grapefruit juice.
Take with or without food.To gain the most benefit, do not miss doses.
Skip the missed dose and go back to your normal time. Do not take 2 doses at the same time or extra doses.

Pregnancy level

C

Related drugs

Flecainide , Quinidine


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