Propafenone adverse effects

Propafenone has some structural similarities to propranolol and possesses weak 3-blocking activity. Its spectrum of action is very similar to that of quinidine, but it does not prolong the action potential. Its sodium channel-blocking kinetics are similar to that of flecainide. Propafenone is metabolized in the liver, with an average half-life of 5-7 hours. The usual daily dosage of propafenone is 450-900 mg in three divided doses. The drug is used primarily for supraventricular arrhythmias. The most common adverse effects are a metallic taste and constipation arrhythmia exacerbation can also occur. 

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CIMETIDINE, RANITIDINE ANTIARRHYTHMICS-AMIODARONE, FLECAINIDE, MEXILETINE, PROCAINAMIDE, PROPAFENONE Likely t plasma concentrations of these antiarrhythmics and risk of adverse effects Cimetidine inhibits CYP2D6-mediated metabolism of flecainide, mexiletine, procainamide and propafenone. Ranitidine is a much weaker CYP2D6 inhibitor. Cimetidine is a potent inhibitor of organic cation transport in the kidney, and the elimination of procainamide is impaired Monitor PR and BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider alternative acid suppression therapy... 

Antidysrhythmic dmgs can themselves cause cardiac dysrhythmias, their major adverse effect. The risk of antidysrhythmic-induced cardiac dysrhythmias (prodys-rhythmic effects) has been estimated at about 11-13% in non-invasive studies (18,19) and at up to 20% in invasive electrophysiological studies. However, the risk varies from dmg to drug and is particularly low with class III drugs. In one study the quoted risks of dysrhythmias were flecainide 30%, quinidine 18%, propafenone 7%, sotalol 6%, and amiodar-one 0% (20). However, amiodarone does cause dysrhythmias, especially when the QT interval is over 600 ms. 

In a comparison of oral aprindine and propafenone in 32 patients (25 men and 7 women, aged 43-82) with paroxysmal or persistent atrial fibrillation, aprindine was effective in five of 29 and propafenone in six of 28 adverse effects were not reported (6). 

A comparison between procainamide and propafenone in 62 patients, who had undergone coronary artery bypass grafting or valvular surgery within 3 weeks and developed sustained atrial fibrillation, showed that both drugs converted the dysrhythmia to sinus rhythm in up to 76% of cases, but that propafenone did it more quickly (3). Symptomatic arterial hypotension occurred more frequently with procainamide (nine of 33 patients) than with propafenone (two of 29 patients). Other adverse effects of procainamide were nausea (n = 2) and junctional escape rhythm (n = 2). 

Propafenone is both a class I antidysrhythmic drug and a beta-adrenoceptor antagonist. Its pharmacological effects, clinical pharmacology, therapeutic uses, adverse effects, and interactions have been reviewed (1-5). 

The beneficial effects were related to these plasma concentrations, as were the time to the first bout of atrial fibrillation, the frequency of bouts of atrial fibrillation, and the time between episodes. However, when atrial fibrillation occurred there was no difference in the ventricular rate in the different groups. Adverse effects necessitated drug withdrawal in four patients one had heart failure and two had gastrointestinal symptoms. These effects were not dose-related, although there were too few occurrences for a definitive conclusion. The authors suggested that this stepwise approach, with increasing doses of propafenone and increasing doses of quinidine could be beneficial in the treatment of paroxysmal atrial fibrillation. 

In a randomized, double-blind, placebo-controlled comparison of propafenone (mean dose 13 mg/kg/day n = 102) and sotalol (mean dose 3 mg/kg/day n = 106) in maintaining sinus rhythm after conversion of recurrent symptomatic atrial fibrillation in 300 patients, efficacy was comparable (13). Tolerable adverse effects in those who took propafenone were gastrointestinal discomfort (n — 15), neurological disturbances (n = 9), a metallic taste (n = 4), and generalized weakness (n = 1) nine patients withdrew owing to adverse effects, four with gastrointestinal disorders, three with dizziness, and two with headache there were no prodysrhythmias. 

Propafenone 450 mg/day and sotalol 240 mg/day have been compared in a placebo-controlled study of 300 patients with atrial fibrillation (14). The two drugs had similar efficacy. There were adverse events in 38 of the patients who took propafenone, compared with 12 of those who took placebo. These included gastrointestinal discomfort, neurological disturbances, asymptomatic bradycardia, a metallic taste, and general weakness. In nine patients the adverse effects were sufficient to cause withdrawal of propafenone. 

The adverse effects of propafenone in placebo-con-trolled trials in patients with atrial tachydysrhythmias have been reviewed (16). The following effects were reported after single intravenous oral doses to produce conversion of atrial fibrillation to sinus rhythm. Non-cardiac adverse effects included mild dizziness. Mild hypotension was also noted, but only required withdrawal of propafenone in one of 29 patients in one study. There have been prodysrhythmic effects in several studies, including atrial flutter with a broad QRS complex, which can occur in up to 5% of cases in some cases atrial flutter can have a rapid ventricular response due to 1 1 atrioventricular conduction, which has been attributed to slowing of atrial conduction and reduced refractoriness of the atrioventricular node. Other prodysrhythmic effects in a few patients included sinus bradycardia with sinus pauses and effects on atrioventricular conduction. 

In patients taking long-term propafenone for supraventricular dysrhythmias adverse effects were more common and have been reported in 14-60% of cases. Cardiac adverse effects were more common in patients with structural heart disease. The non-cardiac effects were either gastrointestinal (nausea, vomiting, taste disturbances) or neurological (dizziness). Adverse effects are dose-related. In one large study there was no difference between propafenone and placebo in the risk of death. 

Cardiovascular adverse effects have been reported in 13-27% of patients taking propafenone and ventricular dysrhythmias in 8-19% in small studies. However, in large studies the risk has been reported to be about 5%. 

The adverse effects of a single oral dose of propafenone for cardioversion of recent-onset atrial fibrillation have been evaluated in a systematic review (18). The adverse effects were transient dysrhythmias (atrial flutter, bradycardia, pauses, and junctional rhythm), reversible widening of the QRS complex, transient hypotension, and mild non-cardiac effects (nausea, headache, gastrointestinal disturbances, dizziness, and paresthesia). 

Adverse effects on the nervous system are common with propafenone and include somnolence, weakness and disorientation, global amnesia (26), dizziness and vertigo, tremor, visual disturbances, and convulsions (SEDA-10,151). 

Unwanted gastrointestinal effects are the most common adverse effects of propafenone, occurring in up to 30% of cases. They include anorexia, nausea and vomiting, dry mouth, a metallic or bitter taste in the mouth, abdominal discomfort, and constipation (SEDA-10,151). 

The incidence of adverse effects of propafenone in children has varied from study to study, but has sometimes been as high as 25%, requiring withdrawal in 6% of cases (39). Elderly people are at increased risk of adverse effects. 

The safety of oral propafenone in the treatment of dysrhythmias has been studied retrospectively in infants and children (40). There were significant electrophysiolo-gical adverse effects and prodysrhythmia in 15 of 772 patients (1.9%). These included sinus node dysfunction in four, complete atrioventricular block in two, aggravation of supraventricular tachycardia in two, acceleration of ventricular rate during atrial flutter in one, ventricular prodysrhythmia in five, and unexplained sjmcope in one. Cardiac arrest or sudden death occurred in five patients (0.6%) two had a supraventricular tachycardia due to Wolff-Parkinson-White syndrome the other three had structural heart disease. Adverse cardiac events were more common in the presence of structural heart disease and there was no difference between patients with supraventricular and ventricular dysrhythmias. 

Propafenone has minimal effects on the pharmacokinetics of intravenous lidocaine, but the severity and duration of the CNS adverse effects of lidocaine are increased. 

Information is limited but the interaetion would seem to be established. Concurrent use need not be avoided but antieipate the need to reduce the dosage of metoprolol and propranolol. Monitor closely because some patients may experience adverse effects. If the suggested mechanism of interaction is correct it is possible (but not confirmed) that other beta blockers that undergo liver metabolism will interact similarly but not those largely excreted unchanged in the urine. See Table 22.1 , (p.833) for the metabolism of some commonly used beta blockers. Also note that propafenone and the beta blockers have negative inotropic effects, which could be additive and result in unwanted cardiodepression. 

A man with major depression responded well to desipramine 175 mg daily with serum desipramine levels in the range of 500 to 1000 nanomol/L. When he was treated for paroxysmal atrial fibrillation with digoxin 250 micrograms daily and propafenone 150 mg twice daily and 300 mg at night he developed markedly elevated serum desipramine levels (2092 nanomol/L) and toxicity (dry mouth, sedation, shakiness) while taking desipramine 150 mg daily. The adverse effects resolved when the desipramine was stopped for 5 days, but when it was restarted at 75 mg daily his serum desipramine levels were still raised (1130 nanomol/L). 

Alboni P, Botto GL, Boriani G, Russo G, Pacchioni F, lori M, Pasanisi G, Mancini M, Mariconti B, Capucci A. Intravenous administration of flecainide or propafenone in patients with recent-onset atrial fibrillation does not predict adverse effects during pill-in-the-pocket treatment. Heart 2010 96(7) 546-9. 

Garcia A. Adverse effects of propafenone after long-term therapy with the addition of citalopram. Am J Geriatr Pharmacother 2008 6(2) 96-9. 

Citalopram An interaction of propafenone with citalopram reportedly caused adverse effects attributable to propafenone, mimicked coronary artery disease [86 ]. 

Boriani G, Biffi M, Diemberger I, Domenichini G, Marziali A, Martignani C. Atrial fibrillation adverse effects of pill-in-the-pocket treatment and propafenone-carvedilol interaction. Int J Cardiol 2010 140(2) 242-3. 

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