propafenone hydrochloride
propafenone hydrochloride
Pharmacologic class: Direct membrane stabilizer
Therapeutic class: Antiarrhythmic (class IC)
Pregnancy risk category C
FDA Box Warning
• In study of patients with asymptomatic, non-life-threatening ventricular arrhythmias who'd had myocardial infarctions more than 6 days but less than 2 years previously, excessive mortality or nonfatal cardiac arrest rate occurred in those treated with encainide or flecainide, compared with patients in carefully matched placebo groups. Given drug's known proarrhythmic properties and lack of evidence of improved survival for any antiarrhythmic in patients without life-threatening arrhythmias, reserve drug for patients with life-threatening ventricular arrhythmias.
Action
Slows conduction velocity in atrio-ventricular (AV) node, decreases automaticity, and increases ratio of effective refractory period to action potential duration; also has mild beta-adrenergic blocking properties
Availability
Tablets: 150 mg, 225 mg, 300 mg
Capsules (sustained-release): 225 mg, 325 mg, 425 mg
Indications and dosages
➣ Patients without structural heart disease to treat life-threatening ventricular arrhythmias; paroxysmal atrial fibrillation or flutter and paroxysmal supraventricular tachycardia associated with disabling symptoms
Adults: Dosage highly individualized based on response and tolerance. Initially, 150 mg P.O. (prompt-release) q 8 hours (450 mg/day); may increase after 3 to 4 days to 225 mg P.O. q 8 hours (675 mg/day) or, if necessary, up to 300 mg P.O. q 8 hours (900 mg/day). Don't exceed 900 mg/day P.O.
➣ Symptomatic atrial fibrillation in patients without structural heart disease
Adults: Dosage individualized based on response and tolerance. Initially, 225 mg P.O. (extended-release) q 12 hours; may increase at 5-day intervals to 325 mg q 12 hours or, if necessary, up to 425 mg q 12 hours.
Dosage adjustment
• Hepatic disease
• Significant widening of the QRS complex or second- or third-degree AV block
• Ventricular arrhythmia with marked previous myocardial damage
• Elderly patients
Contraindications
• Hypersensitivity to drug
• Sinoatrial, AV, and intraventricular disorders of impulse generation or conduction (such as sick sinus node syndrome, AV block) unless artificial pacemaker is in place
• Cardiogenic shock
• Bradycardia
• Uncontrolled heart failure
• Marked hypotension
• Bronchospastic disorders, severe obstructive pulmonary disease
• Electrolyte imbalances
Precautions
Use cautiously in:
• hepatic or renal impairment, myasthenia gravis
• concurrent use of both a CYP2D6 inhibitor and a CYP3A4 inhibitor with extended-release propafenone (avoid use)
• concurrent use of amiodarone or quinidine (not recommended)
• pregnant or breastfeeding patients
• children.
Administration
• Give prompt-release tablets with food (but not with grapefruit juice) in three divided doses daily, once every 8 hours. Give extended-release capsules whole with or without food.
Adverse reactions
CNS: headache, dizziness, drowsiness, syncope, vertigo, confusion, asthenia, speech disturbances, memory loss, ataxia, paresthesia, anxiety, abnormal dreams, insomnia, tremor
CV: palpitations, angina, chest pain, hypotension, bradycardia, premature ventricular contractions, first-degree AV block, supraventricular or ventricular arrhythmias, heart failure, atrial fibrillation, intraventricular conduction delay
EENT: blurred vision, tinnitus
GI: nausea, vomiting, diarrhea, constipation, dyspepsia, abdominal pain or cramps, flatulence, dry mouth, anorexia
GU: reversible disorders of spermatogenesis
Hematologic: purpura, hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia, neutropenia
Hepatic: cholestasis, abnormal hepatic function
Musculoskeletal: muscle weakness, myalgia, leg cramps, myasthenia gravis exacerbation
Respiratory: dyspnea
Skin: rash, alopecia, diaphoresis
Other: altered taste, edema
Interactions
Drug-drug. Amiodarone: conduction and repolarization changes
Beta-adrenergic blockers: increased blood level and effects of beta-adrenergic blockers metabolized by liver
Cimetidine: increased propafenone blood level
CYP1A2 inhibitors (such as amiodarone), CYP2D6 inhibitors (such as desipramine, paroxetine, ritonavir, sertraline), CYP3A4 inhibitors (such as erythromycin, ketoconazole, ritonavir, saquinavir): increased propafenone plasma level
Digoxin, drugs metabolized by CYP2D6 (such as desipramine, haloperidol, imipramine, venlafaxine), warfarin: increased plasma concentrations of these drugs
Lidocaine: increased CNS adverse reactions
Orlistat: reduced propafenone concentration
Quinidine: delayed propafenone metabolism
Rifampin: decreased blood level and antiarrhythmic efficacy of propafenone
Drug-diagnostic tests. Antinuclear antibody: positive titer
Bleeding time: prolonged
Creatine kinase, glucose: increased levels
Granulocytes, white blood cells: decreased counts
Drug-food. Grapefruit juice: increased propafenone plasma level
Patient monitoring
• Monitor ECG and vital signs.
• Evaluate neurologic status. Stay alert for decreasing level of consciousness.
See Monitor CBC and liver function tests. Watch for evidence of blood dyscrasias and abnormal hepatic function.
• Monitor respiratory status for dyspnea.
Patient teaching
• Instruct patient to take prompt-release tablets with food.
• Tell patient to take extended-release capsules whole with or without food and not to crush or divide capsule contents.
See Tell patient which cardiac, neurologic, and respiratory adverse effects to report immediately.
See Instruct patient to immediately report unusual bleeding or bruising.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, vision, and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.