Propafenone

Propafenone hydrochloride extended-release capsules is indicated to prolong the time to recurrence of symptomatic atrial fibrillation (AF) in patients with episodic (most likely paroxysmal or persistent) AF who do not have structural heart disease. Usage Considerations: The use of propafenone hydrochloride extended-release capsules in patients with permanent AF or in patients exclusively with atrial flutter or paroxysmal supraventricular tachycardia (PSVT) has not been evaluated. Do not use propafenone hydrochloride extended-release capsules to control ventricular rate during AF. …

• Propafenone hydrochloride extended-release capsules can be taken with or without food
• Do not crush or further divide the contents of the capsule
• The dose of propafenone hydrochloride extended-release capsules must be individually titrated on the basis of response and tolerance
• Initiate therapy with propafenone hydrochloride extended-release capsules 225 mg given every 12 hours
• Dosage may be increased at a minimum of 5-day intervals to 325 mg given every 12 hours
• If additional therapeutic effect is needed, the dose of propafenone hydrochloride extended-release capsules may be increased to 425 mg given every 12 hours
• In patients with hepatic impairment or those with significant widening of the QRS complex or second- or third-degree AV block, consider reducing the dose
• The combination of cytochrome P450 3A4 (CYP3A4) inhibition and either cytochrome P450 2D6 (CYP2D6) deficiency or CYP2D6 inhibition with the simultaneous administration of propafenone may significantly increase the concentration of propafenone and thereby increase the risk of proarrhythmia and other adverse events
• Therefore, avoid simultaneous use of propafenone hydrochloride extended-release capsules with both a CYP2D6 inhibitor and a CYP3A4 inhibitor [see Warnings and Precautions , Drug Interactions ]
• Initiate therapy with 225 mg given every 12 hours
• Dosage may be increased at a minimum of 5-day intervals to 325 mg every 12 hours and, if necessary, to 425 mg every 12 hours. …

Propafenone hydrochloride extended-release capsules are supplied as hard gelatin capsules containing either 225 mg, 325 mg, or 425 mg of propafenone HCl. The 225-mg strength is brown opaque cap, white opaque body, with "225" imprinted in light blue ink on the body, content is round, white or off-white tablet. …

• The safety and effectiveness of propafenone
• In pediatric patients have not been established

Of the total number of subjects in Phase 3 clinical trials of propafenone hydrochloride extended-release capsules 46% were 65 and older, while 16% were 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals at higher doses cannot be ruled out. …

• Advise the patient to read the FDA-approved patient labeling (Patient Information). • Instruct patients to notify their healthcare providers of any change in over-the-counter, prescription, and supplement use. • Instruct patients to report symptoms that may be associated with altered electrolyte balance, such as excessive or prolonged diarrhea, sweating, vomiting, or loss of appetite or thirst. • Instruct patients not to double the next dose if a dose is missed
• The next dose should be taken at the usual time
• The other brands listed are trademarks of their respective owners and are not trademarks of Vitruvias Therapeutics. …

Propafenone hydrochloride extended-release capsules is contraindicated in the following circumstances: Heart failure Cardiogenic shock Sinoatrial, atrioventricular, and intraventricular disorders of impulse generation or conduction (e.g., sick sinus node syndrome, AV block) in the absence of an artificial pacemaker Known Brugada Syndrome Bradycardia Marked hypotension Bronchospastic disorders or severe obstructive pulmonary disease Marked electrolyte imbalance Heart failure (4) Cardiogenic shock …

Inhibitors of CYP2D6, 1A2, and 3A4 may increase propafenone levels which may lead to cardiac arrhythmias. Simultaneous use with both a CYP3A4 and CYP2D6 inhibitor (or in patients with CYP2D6 deficiency) should be avoided. (7.1) Propafenone may increase digoxin or warfarin levels. (7.2, 7.3) Orlistat may reduce propafenone concentrations. Abrupt cessation of orlistat in patients stable on propafenone hydrochloride extended-release capsules has resulted in convulsions, atrioventricular block, and circulatory failure. (7.4) Concomitant use of lidocaine may increase central nervous system side effects. …

May cause new or worsened arrhythmias. Evaluate patients via ECG prior to and during therapy. (5.1) Propafenone hydrochloride extended-release capsules may unmask Brugada or Brugada-like Syndrome. Evaluate patients via ECG after initiation of therapy. (4, 5.2) Avoid use with other antiarrhythmic agents or drugs that prolong the QT interval. (5.3) Avoid simultaneous use of propafenone with both a cytochrome P450 2D6 (CYP2D6) inhibitor and a 3A4 inhibitor (CYP3A4). (5.4) May provoke overt heart failure. (5.5) May cause dose-related first-degree AV block or other conduction disturbances. Should not be given to patients with conduction defects in absence of a pacemaker. …

The most commonly reported adverse events with propafenone (greater than 5% and greater than placebo) excluding those not reasonably associated with the use of the drug included the following: dizziness, palpitations, chest pain, dyspnea, taste disturbance, nausea, fatigue, anxiety, constipation, upper respiratory tract infection, edema, and influenza. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Vitruvias Therapeutics at 1-844-451-5944 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

8.1 Pregnancy Risk Summary In the absence of studies in pregnant women, available data from published case reports and several decades of postmarketing experience with use of propafenone in pregnancy have not identified any drug-associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. Untreated arrhythmias during pregnancy may pose a risk to the pregnant woman and fetus ( see Clinical Considerations ). …

The symptoms of overdosage may include hypotension, somnolence, bradycardia, intra-atrial and intraventricular conduction disturbances, and rarely, convulsions and high-grade ventricular arrhythmias. Defibrillation, as well as infusion of dopamine and isoproterenol, has been effective in controlling abnormal rhythm and blood pressure. Convulsions have been alleviated with intravenous diazepam. General supportive measures such as mechanical respiratory assistance and external cardiac massage may be necessary. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.