Propafenone - Uses, Dose, Side effects

Propafenone available by the brand name of Rythmol is a class 1C antiarrhythmic drug that has membrane-stabilizing and anesthetic properties.

Indications of propafenone:

  • It is indicated for the treatment of life-threatening ventricular arrhythmias, to prolong the time to recurrence of paroxysmal atrial fibrillation/ flutter or paroxysmal supraventricular tachycardia in patients with disabling symptoms without structural heart disease

  • Extended-release capsule:

    • It is useful for prolonging the time to recurrence of symptomatic atrial fibrillation in patients without structural heart disease.

  • Off Label Use of Propafenone in Adults:

    • Paroxysmal atrial fibrillation (pharmacological cardioversion);
    • Ventricular premature beats

Propafenone dose in adults:

Note:

Dose reduction is required for patients with a significant widening of QRS complex or second- or third-degree AV block.

Propafenone dose in the treatment of Atrial fibrillation to prevent recurrence:

  • Extended-release capsule:

    • Initial: 225 mg per oral every 12 hours;
    • The dosage increase may be made at a minimum of 5-day intervals;
    • The dose may be increased to 325 mg every 12 hours;
    • if a further increase is necessary, the dose may be increased to 425 mg every 12 hours.

  • Immediate-release tablet:

    • Initial: 150 mg per oral every 8 hours;
    • Dosage increase may be made at a minimum of 3- to 4-day intervals, may increase to 225 mg every 8 hours;
    • If a further increase is necessary, may increase to 300 mg every 8 hours.

Propafenone dose in the treatment of Paroxysmal supraventricular tachycardia to prevent recurrence:

  • Immediate-release tablet:

    • Initial: 150 mg per oral every 8 hours;
    • The dosage may be increased at a minimum of 3- to 4-day intervals to 225 mg every 8 hours;
    • If a further increase is necessary, may increase to 300 mg every 8 hours.

  • Alternate recommendations:

    • Immediate-release tablet:

      • Initial: 150 mg per oral every 8 hours;
      • The maximum maintenance dose: 300 mg every 8 hours.

    • Extended-release capsule:

      • Initial: 225 mg per oral every 12 hours
      • maximum maintenance dose: 425 mg every 12 hours.

Propafenone (Rythmol) dose for the pharmacologic cardioversion of Paroxysmal atrial fibrillation:

Note:

  • May be used on an outpatient basis (“Pill-in-the-pocket”).
  • The patient must be taking an AV nodal-blocking agent (eg, Beta-blocker, non-dihydropyridine calcium channel blocker) before starting antiarrhythmic.

  • Immediate-release tablet:

    • weight <70 kg:
      • 450 mg
    • weight ≥70 kg:
      • 600 mg
    • May not repeat in ≤24 hours

Propafenone (Rythmol) dose in the treatment of Ventricular arrhythmia:

  • Immediate-release tablet:

    • 150 mg per oral every 8 hours; dosage increase may be made at a minimum of 3- to 4-day intervals, may increase to 225 mg every 8 hours;
    • If a further increase is necessary, may increase to 300 mg every 8 hours.

  • Extended-release capsule (off- label dose):

    • 225 to 425 mg per oral every 12 hours.

Propafenone (Rythmol) dose in the treatment of Ventricular premature beats: 

  • Immediate-release tablet:

    • 150 to 300 mg per oral every 8 hours

  • Extended-release capsule:

    • 225 to 425 mg  per oral every 12 hours

Dose in Children:

The safety and efficacy of the drug in children has not been established.

Pregnancy Risk Category: C

  • The placenta is crossed by propafenone and 5-hydroxypropafenone, and they can be detected in the infant.
  • It should not be administered in any way and should be avoided during the first trimester.
  • For supraventricular tachycardia symptomatic, propafenone may be administered to pregnant women.
  • It is also helpful in preventing supraventricular tachycardia in patients with Wolff-Parkinson-White syndrome.
  • Propafenone should not be used as a first-line treatment. It is only recommended to treat arrhythmias in cases where other medications are not available.
  • It can lead to a reversible impairment in spermatogenesis for males.

Propafenone use during breastfeeding:

  • Breast milk contains propafenone as well as the 5-hydroxypropafenone metabolism.
  • According to the case report, the relative infant dose (RID), of propafenone was 1% of weight-adjusted mother dose.
  • When the relative infant dose for a medication is less than 10%, breastfeeding is permitted.
  • Milk concentrations were 32 ng/mL (propafenone) and 47 ng/mL (5hydroxypropafenone).
  • Based on actual maternal weight, one author calculated that the RID was 0.03%. Another author estimated it to be 0.1%.
  • The milk was sipped at intervals of 1 to 12 hours following the last dose, regardless of postpartum age.
  • According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks and benefits to the baby as well as the benefits to the mother.

Dose adjustment in renal disease:

50% of propafenone metabolites are excreted in the urine, however there are no dosage adjustments provided in the manufacturer's labeling

Hemodialysis/CVVH:

  • Minimally dialyzable , supplemental dose not necessary

Dose adjustment in liver disease:

There are no dosage adjustment provided in the manufacturer’s labeling; however, dosage reduction is necesssary as drug undergoes hepatic metabolism. In patients with mild to moderate liver impairment, the following dosing recommendations have been made:

  • Initial: 150 mg once daily; if necessary, the dose may be increased by 150 mg/day in divided doses (eg, b.i.d or t.i.d) at a minimum of 4-day intervals up to a maximum of 300 mg every 12 hours.

Common Side Effects of Propafenone:

  • Central Nervous System:

    • Unusual Taste
    • Dizziness

  • Gastrointestinal:

    • Nausea
    • Vomiting

Side Effects Of Propafenone Include:

  • Cardiovascular:

    • Cardiac Arrhythmia
    • Angina Pectoris
    • Cardiac Failure
    • First Degree Atrioventricular Block
    • Palpitations
    • Ventricular Tachycardia
    • Bradycardia
    • Chest Pain
    • Widened QRS Complex On ECG
    • Syncope
    • Ventricular Premature Contractions
    • Atrial Fibrillation
    • Bundle Branch Block
    • Edema
    • Cardiac Conduction Delay
    • Hypotension

  • Central Nervous System:

    • Fatigue
    • Headache
    • Ataxia
    • Insomnia
    • Anxiety
    • Drowsiness

  • Dermatologic:

    • Skin Rash
    • Diaphoresis

  • Gastrointestinal:

    • Constipation
    • Diarrhea
    • Dyspepsia
    • Abdominal Pain
    • Anorexia
    • Xerostomia
    • Flatulence

  • Neuromuscular & Skeletal:

    • Weakness
    • Arthralgia
    • Tremor

  • Ophthalmic:

    • Blurred Vision

  • Respiratory:

    • Dyspnea

Contraindications to Propafenone:

  • Hypersensitivity to propafenone and any component of the formulation
  • Cardiac failure
  • Cardiogenic shock
  • Bradycardia/ severe hypertension
  • COPD severe
  • Severe electrolyte imbalance
  • A, A.V, and intraventricular disorders in impulse generation or conduction.
  • Liver impairment severe
  • Myasthenia gravis
  • Concurrent use of ritonavir

Warnings and precautions

  • Agranulocytosis

    • Sometimes, granulocytosis may occur. It returns to normal within 2 weeks after therapy is stopped.

  • CNS effects

    • Propafenone can cause blurred vision, dizziness, fatigue and dizziness. Patients should be cautious about driving or operating machinery.

  • Conduction disturbances:

    • It can lead to prolonged PR, longer QRS duration, or slow atrioventricular Conduction, leading to first-degree AV block.

  • Titers of elevated antinuclear antibodies

    • Positive antinuclear antibodies (ANA) were detected in some patients who received propafenone. However, not all of these cases resulted in drug-induced Lupus Erythematosus.
    • The decrease in titers is seen regardless of discontinuation of therapy. However, discontinuation is required for patients who are symptomatic and have positive ANA titers.

  • Hepatotoxicity:

    • Hepatocellular injury, cholestasis and other causes of life-threatening liver abnormalities can lead to serious consequences.

  • Proarrhythmic effects

    • Propafenone has been shown to prolong QT, ventricular fibrillation and asystole.
    • To prevent QT prolongation, monitoring and dose adjustment are essential.

  • Brugada syndrome:

    • Brugada Syndrome may be unmaskable by Propafenone.
    • ECG should be performed after treatment initiation. Therapy should be stopped in Brugada Syndrome.

  • Electrolyte imbalance:

    • Patients with electrolyte abnormalities not corrected are advised to avoid use.
    • It is important to correct electrolyte imbalances, especially hypokalemia and hypomagnesemia, before treatment.

  • Heart failure (HF):

    • Propafenone can cause heart failure so it is best to avoid it.

  • Hepatic impairment

    • Patients with hepatic impairment should be cautious.

  • Myasthenia gravis:

    • Patients with myasthenia Gravis should be cautious. It may worsen the condition.

  • Pulmonary disease

    • Patients with obstructive pulmonary disease can receive propafenone without bronchospasm.
    • However, severe obstructive pulmonary disease is where it is contraindicated.

  • Renal impairment

    • Patients with impaired renal function should be cautious.

Propafenone: Drug Interaction

Risk Factor C (Monitor therapy)

Antihepaciviral Combination Products

May increase the serum concentration of Propafenone. Management: Canadian labeling recommends avoiding this combination.

ARIPiprazole

CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations.

Beta-Blockers

Propafenone may increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Exceptions: Atenolol; Carteolol (Ophthalmic); Levobunolol; Metipranolol; Nadolol.

Bradycardia-Causing Agents

May enhance the bradycardic effect of other Bradycardia-Causing Agents.

Brentuximab Vedotin

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased.

Bretylium

May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents.

Cardiac Glycosides

Propafenone may increase the serum concentration of Cardiac Glycosides.

Celiprolol

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol.

Cimetidine

May increase the serum concentration of Propafenone.

CloBAZam

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Cobicistat

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

CYP2D6 Inhibitors (Moderate)

May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).

CYP2D6 Inhibitors (Moderate)

May increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Exceptions: Thioridazine.

CYP3A4 Inducers (Strong)

May decrease the serum concentration of Propafenone.

CYP3A4 Inhibitors (Moderate)

May increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Exceptions: Crizotinib; Erythromycin (Systemic); Fluconazole; Nilotinib; Ribociclib.

CYP3A4 Inhibitors (Strong)

May increase the serum concentration of Propafenone. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Exceptions: Clarithromycin; Saquinavir; Voriconazole.

Darunavir

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Etravirine

May decrease the serum concentration of Propafenone.

Everolimus

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus.

FLUoxetine

Propafenone may enhance the QTc-prolonging effect of FLUoxetine. FLUoxetine may increase the serum concentration of Propafenone.

FluvoxaMINE

May increase the serum concentration of Propafenone.

Haloperidol

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTcprolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Imatinib

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Ivabradine

Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine.

Lacosamide

Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide.

Lacosamide

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased.

Larotrectinib

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib.

Lumefantrine

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Midodrine

May enhance the bradycardic effect of Bradycardia-Causing Agents.

Mirabegron

May increase the serum concentration of Propafenone. Management: Monitor clinical response to propafenone closely. Dose adjustment may be necessary. Canadian mirabegron labeling recommends restricting the maximum adult mirabegron dose to 25 mg/day in patients receiving propafenone.

Naldemedine

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine.

Naloxegol

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol.

Ondansetron

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTcprolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Orlistat

May decrease the serum concentration of Propafenone.

Panobinostat

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

PARoxetine

May increase the serum concentration of Propafenone.

Peginterferon Alfa-2b

May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

Pentamidine (Systemic)

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Perhexiline

CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline.

Perhexiline

CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).

P-glycoprotein/ABCB1 Substrates

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide.

Propranolol

Propafenone may increase the serum concentration of Propranolol.

Prucalopride

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride.

QT-prolonging Antidepressants (Moderate Risk)

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Antipsychotics (Moderate Risk)

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Pimozide.

QT-prolonging Class IC Antiarrhythmics (Moderate Risk)

May enhance the QTc-prolonging effect of other QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Kinase Inhibitors (Moderate Risk)

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Miscellaneous Agents (Moderate Risk)

May enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone.

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Quinolone Antibiotics (Moderate Risk)

May enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk)

QT-prolonging Class IC Antiarrhythmics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Ranolazine

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine.

RifAXIMin

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin.

Ruxolitinib

May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible.

Sertraline

May enhance the QTc-prolonging effect of Propafenone. Sertraline may increase the serum concentration of Propafenone.

Silodosin

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin.

Simeprevir

May increase the serum concentration of Propafenone.

St John's Wort

May decrease the serum concentration of Propafenone.

Talazoparib

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs.

Tegaserod

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod.

Terlipressin

May enhance the bradycardic effect of Bradycardia-Causing Agents.

Theophylline Derivatives

Propafenone may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline.

Tofacitinib

May enhance the bradycardic effect of Bradycardia-Causing Agents.

Venlafaxine

Propafenone may increase the serum concentration of Venlafaxine. Management: Monitor for increased venlafaxine levels/adverse effects (e.g., hallucinations, agitation, confusion) with propafenone initiation/dose increase. Conversely, monitor for decreased venlafaxine levels with profapenone discontinuation/dose decrease.

Vitamin K Antagonists (eg, warfarin)

Propafenone may increase the serum concentration of Vitamin K Antagonists.

Risk Factor D (Consider therapy modification)

Abiraterone Acetate

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.

Afatinib

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling recommends avoiding combination if possible. Iif used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib.

Amiodarone

May enhance the QTc-prolonging effect of Propafenone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Betrixaban

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor.

Bilastine

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors.

Colchicine

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details.

CYP2D6 Inhibitors (Strong)

May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).

Dabigatran Etexilate

P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling.

Dacomitinib

May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index.

Domperidone

QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

DOXOrubicin (Conventional)

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.

Edoxaban

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation.

Lefamulin

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects.

Methadone

Propafenone may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Class IA Antiarrhythmics (Highest Risk)

Propafenone may enhance the QTcprolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Class III Antiarrhythmics (Highest Risk)

Propafenone may enhance the QTcprolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Kinase Inhibitors (Highest Risk)

Propafenone may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

QT-prolonging Miscellaneous Agents (Highest Risk)

Propafenone may enhance the QTcprolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.

Siponimod

Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia.

TiZANidine

CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions.

Venetoclax

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors.

Risk Factor X (Avoid combination)

Asunaprevir

May increase the serum concentration of Propafenone.

Fosamprenavir

May increase the serum concentration of Propafenone. Management: Concurrent use of ritonavir-boosted fosamprenavir with propafenone is contraindicated. The use of non-ritonavir-boosted fosamprenavir with propafenone is not specifically contraindicated but should only be undertaken with caution.

PAZOPanib

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib.

Pimozide

May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk).

Ritonavir

May increase the serum concentration of Propafenone.

Tipranavir

May increase the serum concentration of Propafenone.

Topotecan

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan.

VinCRIStine (Liposomal)

P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal).

Monitoring parameters:

  • BP
  • Pulse
  • ECG

How to administer Propafenone (Rythmol)?

  • Capsules should be taken orally swallowed as a whole without regards to food, without crushing or chewing.
  • The Canadian labeling recommends the tablet be swallowed whole with liquid and to be administered with food. 

Mechanism of action of Propafenone (Rythmol):

  • Propafenone, a class 1c antiarrhythmic drug, has local anesthetic properties. 
  • It slows down the rate of action and blocks the fast-inward sodium current.
  • It prolongs conduction and refractoriness in all myocardium areas, focusing primarily on intraventricular conduction.
  • It can cause spontaneous automaticity reductions and prolonged refractory periods. Additionally, it may exhibit some beta-blockade activity.

Absorption: Well absorbed

Protein binding: 95% to alpha -acid glycoprotein

Metabolism: occurs in the liver via CYP2D6, CYP3A4, and CYP1A2 to two active metabolites (5hydroxypropafenone and N-depropylpropafenone) then ultimately to glucuronide or sulfate conjugates. Two genetically determined metabolism groups exist (extensive and poor metabolizers); 10% of Caucasians are poor metabolizers. Exhibits nonlinear pharmacokinetics. Serum concentrations are increased to tenfold when the dose is increased from 300-900 mg/day, this nonlinearity is thought to be due to saturable first-pass effect.

Bioavailability:

  • Immediate release (IR): 150 mg: 3.4%; 300 mg: 10.6%; relative bioavailability of extended-release (ER) capsule is less than immediate-release tablet; The bioavailability of an ER capsule regimen of 325 mg twice-daily regimen approximates an IR tablet regimen of 150 mg 3 times/day.

Half-life elimination:

  • Extensive metabolizers: 2-10 hours
  • Poor metabolizers: 10-32 hours

The time to reach peak serum concentration:

  • Immediate-release: 3.5 hours
  • Extended-release: 3-8 hours

Excretion: Urine (<1% unchanged; remainder as glucuronide or sulfate conjugates); feces

Propafenone Brand Names (International):

  • Rythmol SR
  • Rythmol
  • APO-Propafenone
  • MYL-Propafenone
  • MYLAN-Propafenone
  • NU-Propafenone
  • PMSPropafenone
  • Propafenone-150
  • Propafenone-300
  • Arythmol
  • Nistaken
  • Norfenon
  • Normapafenone
  • Normorytmin
  • Profex
  • Pronon
  • Propafen
  • Propafenon Genericon
  • Propafenon Pharmavit
  • Propanorm
  • Prorynorm
  • Rhythmonorm
  • Ritmocor
  • Ritmonorm
  • Rythmex
  • Rythmol
  • Rythmonorm
  • Rythmosin
  • Rytmocard
  • Rytmol
  • Rytmonorm
  • Rytmonorma
  • Ryytmonorm

Propafenon Brand Names in Pakistan:

No Brands Available in Pakistan.

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