No

Antiarrhythmic Agent, Class I-C

Life-threatening ventricular arrhythmias

C

Hypersensitivity to propafenone or any component; sinoatrial, AV, and intraventricular disorders of impulse generation and/or conduction (except in patients with a functioning artificial pacemaker); sinus bradycardia; cardiogenic shock; uncompensated cardiac failure; hypotension; bronchospastic disorders; uncorrected electrolyte abnormalities

Monitor for proarrhythmic events. Patients with bronchospastic disease should generally not receive this drug. Monitor for worsening CHF if patient has underlying condition. Can cause or unmask a variety of conduction disturbances. May alter pacing and sensing thresholds of artificial pacemakers. Administer cautiously in significant hepatic dysfunction.

1% to 10%:

Central nervous system: Dizziness (4% to 15%), fatigue (2% to 6%), headache (2% to 5%), weakness (1% to 2%), ataxia (0% to 2%), insomnia (0% to 2%), anxiety (1% to 2%), drowsiness (1%)

Cardiovascular: New or worsened arrhythmias (proarrhythmic effect) (2% to 10%), angina (2% to 5%), congestive heart failure (1% to 4%), ventricular tachycardia (1% to 3%), palpitations (1% to 3%), AV block (first-degree) (1% to 3%), syncope (1% to 2%), increased QRS interval (1% to 2%), chest pain (1% to 2%), PVCs (1% to 2%), bradycardia (1% to 2%), edema (0% to 1%), bundle branch block (0% to 1%), atrial fibrillation (1%), hypotension (0% to 1%), intraventricular conduction delay (0% to 1%)

Dermatologic: Rash (1% to 3%)

Gastrointestinal: Nausea/vomiting (2% to 11%), unusual taste (3% to 23%), constipation (2% to 7%), dyspepsia (1% to 3%), diarrhea (1% to 3%), xerostomia (1% to 2%), anorexia (1% to 2%), abdominal pain (1% to 2%), flatulence (0% to 1%)

Neuromuscular & skeletal: Tremor (0% to 1%), arthralgia (0% to 1%)

Ocular: Blurred vision (1% to 6%)

Respiratory: Dyspnea (2% to 5%)

Miscellaneous: Diaphoresis (1%)

<1% (Limited to important or life-threatening symptoms): Agranulocytosis, leukopenia, thrombocytopenia, purpura, granulocytopenia, anemia, increased bleeding time, hepatitis (0.03%), increased serum transaminases (0.2%), prolonged PR interval, sinus node dysfunction, cholestasis (0.1%), gastroenteritis, positive ANA titers (0.7%), lupus erythematosus, AV block (second or third degree), AV dissociation, cardiac arrest, flushing, sinus arrest, flushing, abnormal speech, abnormal dreams, abnormal vision, apnea, coma, confusion, depression, memory loss, paresthesia, numbness, psychosis, seizures (0.3%), tinnitus, abnormal smell sensation, vertigo, alopecia, eye irritation, SIADH, hyponatremia, impotence, hyperglycemia, kidney failure, muscle cramps, muscle weakness, nephrotic syndrome, pain, pruritus, congestive heart failure, renal failure, nephrotic syndrome

Case reports: Peripheral neuropathy, mania, amnesia

Has a narrow therapeutic index and severe toxicity may occur slightly above the therapeutic range, especially if combined with other antiarrhythmic drugs. Acute single ingestion of twice the daily therapeutic dose is life-threatening. Symptoms of overdose include increases in P-R, QRS, Q-T intervals and amplitude of the T wave, A-V block, bradycardia, hypotension, ventricular arrhythmias (monomorphic or polymorphic ventricular tachycardia), and asystole; other symptoms include dizziness, blurred vision, headache, and GI upset.

Treatment is supportive, using conventional treatment (fluids, positioning, anticonvulsants, antiarrhythmics). Note: Type Ia antiarrhythmic agents should not be used to treat cardiotoxicity caused by type 1c drugs; sodium bicarbonate may reverse QRS prolongation, bradycardia and hypotension; ventricular pacing may be needed; hemodialysis only of possible benefit for tocainide or flecainide overdose in patients with renal failure.

CYP2D6 substrate/inhibitor, CYP1A2 substrate

Amprenavir and ritonavir may increase propafenone levels; concurrent use is contraindicated.

Cimetidine increases propafenone blood levels.

Digoxin blood levels are increased; monitor for toxicity

Enzyme inducers (phenobarbital, phenytoin, rifabutin, rifampin) may decrease propafenone blood levels.

Metoprolol blood levels are increased.

Propranolol blood levels are increased.

Quinidine increases propafenone blood levels.

Theophylline blood levels may be increased.

Warfarin blood levels are increased; response may be increased. Monitor INR closely.

Propafenone is a 1C antiarrhythmic agent which possesses local anesthetic properties, blocks the fast inward sodium current, and slows the rate of increase of the action potential. prolongs conduction and refractoriness in all areas of the myocardium, with a slightly more pronounced effect on intraventricular conduction; it prolongs effective refractory period, reduces spontaneous automaticity and exhibits some beta-blockade activity.

Absorption: Well absorbed

Metabolism: Two genetically determined metabolism groups exist: fast or slow metabolizers; 10% of Caucasians are slow metabolizers

Half-life after a single dose (100-300 mg): 2-8 hours; half-life after chronic dosing ranges from 10-32 hours

Time to peak: Peak levels occur in 2 hours with a 150 mg dose and 3 hours after a 300 mg dose; this agent exhibits nonlinear pharmacokinetics; when dose is increased from 300 mg to 900 mg/day, serum concentrations increase tenfold; this nonlinearity is thought to be due to saturable first-pass hepatic enzyme metabolism

Adults: Oral: 150 mg every 8 hours, increase at 3- to 4-day intervals up to 300 mg every 8 hours. Note: Patients who exhibit significant widening of QRS complex or second- or third-degree A-V block may need dose reduction.

Administer at the same time in relation to meals each day, either always with meals or always between meals

EKG, blood pressure, pulse (particularly at initiation of therapy)

Propafenone is a Class Ic antiarrhythmic with very weak beta-blocking properties. As with other Type 1c agents, it is therefore prudent to avoid propafenone use in patients with cardiovascular disease, particularly recent myocardial infarction and heart failure, due to a possible increase in proarrhythmia and mortality.

Dizziness and drowsiness are common; may cause anxiety

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; use TCAs with caution; may cause QT prolongation

No information available to require special precautions

>10% of patients experience significant dry mouth; normal salivary flow will resume with cessation of drug therapy

Take exactly as directed; do not take additional doses or discontinue without consulting prescriber. You will need regular cardiac checkups and blood tests while taking this medication. You may experience dizziness, drowsiness, or visual changes (use caution when driving or engaging in tasks requiring alertness until response to drug is known); abnormal taste, nausea or vomiting, or loss of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); headaches (prescriber may recommend mild analgesic); or diarrhea (exercise, yogurt, or boiled milk may help - if persistent consult prescriber). Report chest pain, palpitation, or erratic heartbeat; difficulty breathing, increased weight or swelling of hands or feet; acute persistent diarrhea or constipation; or changes in vision. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Patients should be on a cardiac monitor during initiation of therapy or when dosage is increased; monitor heart sounds and pulses for rate, rhythm and quality

Tablet, as hydrochloride: 150 mg, 225 mg, 300 mg

Burgess ED and Duff HJ, "Hemodialysis Removal of Propafenone," Pharmacotherapy, 1989, 9(5):331-3.

Galasso PJ, Stanton MS, and Vogel H, "Propafenone-Induced Peripheral Neuropathy," Mayo Clin Proc, 1995, 70(5):469-72.

Jones RJ, Brace SR, and Vander Tuin EL, "Probable Propafenone-Induced Transient Global Amnesia," Ann Pharmacother, 1995, 29(6):586-90.

McHugh TP and Perina DG, "Propafenone Ingestion," Ann Emerg Med, 1987, 16(4):437-40.