Dosing and uses of Rythmol (propafenone)
Adult dosage forms and strengths
tablet
- 150mg
- 225mg
- 300mg
capsule, extended-release
- 225mg
- 325mg
- 425mg
Ventricular Arrhythmias/Paroxysmal Supraventricular Tachycardia
IR: 150 mg PO q8hr; may increase to 225 mg q8hr after 3-4 days, and, if required, 300 mg q8hr; not to exceed 300 mg q8hr
Atrial Fibrillation/Flutter
IR: 150 mg PO q8hr; may increase to 225 mg q8hr after 3-4 days, and, if required, 300 mg q8hr; not to exceed 300 mg q8hr
ER: 225 mg PO q12hr initially; may increase dose q5Days to 325 mg PO q12hr OR 425 mg PO q12hr, if necessary
Dosing Considerations
Reduce dose in patients with significant widening of the QRS complex or 2nd or 3rd degree AV block
Dosing Modifications
Renal impairment: Not studied
Hepatic impairment: Administer 20-30% of normal IR dose and monitor closely; consider dose reduction if administering ER dose
Pediatric dosage forms and strengths
Safety and efficacy not established
Rythmol (propafenone) adverse (side) effects
>10%
Unusual taste (7-23%)
Dizziness/lightheadedness (7-15%)
N/V (3-11%)
1-10%
Constipation (4-8%)
Headache (2-6%)
Intraventricular conduction delay (4%)
Fatigue (6%)
Blurred vision (3%)
Weakness (3%)
Dyspnea (2%)
Wild complex tachycardia (2%)
Bradycardia (2%)
Palpitations (2%)
Tremor (2%)
Anorexia (2%)
Diarrhea (2%)
Ataxia (2%)
1°AV block (2-5%)
Angina (5%)
Palpitations (3%)
CHF (2-3% )
Chest pain (2%)
Bradyarrhythmia (2%)
AF (1%)
Bundle branch block (1%)
2nd degree AV block (1%)
Hypotension (1%)
Sinus arrest (1%)
Frequency not defined
Lethargy
Rash
Dyspepsia
Dry mouth
Agranulocytosis
Hepatotoxicity (rare)
Systemic lupus erythematosus (rare)
Bronchospasm (rare)
Postmarketing Reports
Cardiovascular: Atrial flutter, AV dissociation, cardiac arrest, flushing, hot flashes, sick sinus syndrome, sinus pause or arrest, supraventricular tachycardia
Neurologic/psychiatric: Abnormal dreams/speech/vision, apnea, coma, confusion, depression, memory loss, numbness, paresthesias, psychosis/mania, seizures, tinnitus, unusual smell sensation, vertigo
Hepatic: Cholestasis, elevated LFTs, gastroenteritis, hepatitis
Hematologic: Agranulocytosis, anemia, bruising, granulocytopenia, increased bleeding time, leukopenia, purpura, thrombocytopenia
Alopecia
Eye irritation
Hyponatremia/inappropriate ADH secretion
Impotence
Increased glucose
Kidney failure
Positive ANA
Lupus erythematosus
Muscle cramps
Muscle weakness
Nephrotic syndrome
Pain
Pruritus
Warnings
Black box warnings
NHLBI’s Cardiac Arrhythmia Suppression Trial (CAST): Excessive mortality or nonfatal cardiac arrest (7.7%) shown with encainide or flecainide, compared with placebo (3%)
Applicability of CAST results to other populations (eg, patients without recent MI) is uncertain; therefore, reserve use of class IC antiarrhythmics for life-threatening ventricular arrhythmias
Considering known proarrhythmic properties of propafenone and lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, use should be reserved for patients with life-threatening ventricular arrhythmias
Contraindications
Hypersensitivity
Bradycardia, asthma/bronchospastic disorders or severe obstructive pulmonary disease, marked hypotension, cardiogenic shock, intraventricular disorders of impulse generation and/or conduction including sick sinus node and syndrome AV block (unless artificial pacemaker present), electrolyte imbalances, CHF, severe hypotension, myasthenia gravis
Known Brugada syndrome
Concomitant ritonavir therapy
Cautions
May alter pacemaker thresholds
Elevated ANA titers reported with use; may consider discontinuing therapy in symtomatic patients with positive ANA titers
Use caution in patients with hematologic disorders, myasthenia gravis (may exacerbate condition), hepatic/renal impairment
Use with caution in patients with hypersensitivity to propranoloL
There is a potential for increased mortality post-MI, as with encainide and flecainide (other class ICs)
May cause life-threatening drug-induced arrhythmias including assytole, ventricular fibrillation, ventricular tachycardia, and torsade de pointes
Through CYP3A inhibition, grapefruit juice consumption may decrease elimination (ie, increase serum levels)
Correct electrolyte imbalance, especially hypomagnesemia or hypokalemia before initiating therapy and throughout
Plasma concentration has poor correlation to antiarrhythmia effect
New or worsening HF may occur
Slows AV conduction and may cause AV block
Brugada syndrome may be unmasked after exposure to propafenone; perform ECG after initiation and discontinue the drug if changes are suggestive of Brugada Syndrome
Agranulocytosis reported (most within first 2 months of treatment)
Highly metabolized by liver; severe liver impairment increases bioavailability by 70%
Pregnancy and lactation
Pregnancy category: C
Lactation: Crosses into breast milk; discontinue drug or do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Rythmol (propafenone)
Mechanism of action
Class IC antiarrhythmic; slows conduction in cardiac tissue by altering transport of ion across membranes; causes slight prolongation of AV nodal refractory periods; decreases rate of rise of action potential without affecting its duration
Absorption
Bioavailability: 3.4% (150 mg IR); 10.6% (300 mg IR)
Peak serum time: 2-3.5 hr (IR); 3-8 hr (ER)
Distribution
Protein bound: 95%
Vd: 252 L (adults)
Metabolism
Metabolism: Via CYP2D6 to 5-hydroxypropafenone; via CYP1A2 and CYP3A4 to N-depropylpropafenone
Metabolites: 5-hydroxypropafenone (active), N-depropylpropafenone (active), at least 9 other metabolites
Enzymes inhibited: CYP2D6
Elimination
Half-life: 2-10 hr (extensive metabolizers); 10-32 hr (poor metabolizers)
Dialyzable: No (HD)
Total body clearance: 1-1.3 L/kg/hr
Excretion: Urine; feces
Pharmacogenomics
Approximately 7-10% of whites and 3-8% of African Americans lack the capacity to metabolize CYP2D6 substrates and are classified as poor metabolizers (PMs)
Increased exposure may lead to cardiac arrhythmias and exaggerated beta-adrenergic blocking activity
Because of propafenone’s metabolism by CYP2D6, deficiency of this isoenzyme is potentially hazardous
Genetic testing laboratories
- The Roche Cytochrome AmpliChip P450 2D6/2C19 Genotyping and Phenotyping Assay can be used to identify 26 different alleles of CYP2D6
- LabCorp (https://www.labcorp.com/); testing for CYP2D6 variants
