Propafenone toxicity

Plasma metoprolol and propranolol levels can be markedly raised (two to fivefold) by propafenone. Toxicity may develop. 

Drug-drug interactions Verapamil Verapamil may have precipitated propafenone toxicity [67 ]. 

Yeung A, Shanks D, Parwana H, Gin K. Acute propafenone toxicity after two exposures at standard dosing. Can J Cardiol 2010 26(6) 209-10. 

PROPAFENONE ANTICANCER AND IMMUNOMODULATING DRUGS-CICLOSPORIN Possible t cidosporin levels Uncertain Watch for signs of cidosporin toxicity... 

PROPAFENONE METOPROLOL, PROPANOLOL t plasma levels of propranolol and metoprolol Propafenone is extensively metabolized by CYP2D6 enzymes and interferes with the metabolism of propranolol and metoprolol Watch for propranolol and metoprolol toxicity 1 doses accordingly... 

PROPAFENONE BRONCHODILATORS -THEOPHYLLINE Cases oft theophylline levels with toxicity when propafenone added Uncertain at present Watch for signs of theophylline toxicity... 

PROPAFENONE CARDIAC GLYCOSIDES Digoxin concentrations may be t by propafenone Uncertain at present Watch for digoxin toxicity check digoxin levels if indicated and 1 digoxin dose as necessary (15-75% suggested by studies)... 

IMATINIB 1. ANTIARRHYTHMICS -flecainide, mexiletine, propafenone 2. ANTIDEPRESSANTS - fluoxetine, paroxetine, TCAs, trazodone, venlafaxine 3. ANTIPSYCHOTICS -clozapine, haloperidol, perphenazine, risperidone, thioridazine 4. BETA-BLOCKERS - metoprolol, propanolol, timolol 5. DONEPEZIL 6. METHAMPHETAMINE Imatinib may cause t plasma concentrations of these drugs, with a risk of toxic effects Inhibition of CYP2D6-mediated metabolism of these drugs Watch for early features of toxicity of these drugs... 

CANNABIS PROPAFENONE Unpredictable changes in plasma concentration. Risk of toxicity or therapeutic failure, particularly of drugs with a narrow therapeutic index Induction or inhibition of CYP3A4-mediated metabolism by cannabis. It is not yet known whether the effects are dependent on the degree of cannabis consumption Be aware. Watch for signs of toxicity especially when cannabis use abruptly changes... 

The CNS toxicity of lidocaine was increased in 11 healthy volunteers who simultaneously received propafenone, which reduced the metabolism of lidocaine (81). 

Therapeutic benefit is most likely when the plasma propafenone concentration is in the range 0.5-2.0 mg/ ml, although the correlation is poor (47), and there is a large overlap between therapeutic and toxic concentrations (32). The therapeutic effect of propafenone correlates better with prolongation of the PR and QRS intervals (48). 

Coadministration of quinidine may predispose to digoxin toxicity. However, other antiarrhythmic drugs can also increase serum concentrations of digoxin by modifying either its renal (quinidine) or non-renal (quinidine, verapamil, amiodarone and propafenone) excretion (Muir Mcguirk 1985). 

Propafenone Serum concentrations and/or toxicity may be increased by fluoxetine and fluvoxamine. 

Although nearly every type I or III antiarrhythmic drug has some published evidence of effectiveness in preventing recurrences of atrial fibrillation, amiodarone is clearly the most effective agent and now the most frequently chosen despite its impressive toxicity. Initially, uncontrolled studies indicated that low doses (100 to 200 mg/day) of amiodarone are effective. Later, in a comparative trial,amiodarone was shown to be superior to either sotalol or propafenone in maintaining sinus rhythm. Further, in a substudy of AFFIRM,amiodarone was demonstrated to be the most effective antiarrhythmic agent of those used in the study. 

Lee, B. L. and Dohrmann, M. L., Theophylline toxicity after propafenone treatment evidence for drug interaction, Clin. Pharmacol. Then, 51(3) 353-355, 1992. 

In a preliminary report of a study in 7 non-smoking subjects who were fast metabolisers of propafenone, phenobarbital 100 mg daily for 3 weeks reduced the levels of a single 300-mg dose of propafenone by 26 to 87% and the AUC by 10 to 89%. The intrinsic clearance inereased by 11 to 84%. The results in a further 4 heavy smokers were similar. These ehanges probably occur because phenobarbital (a potent stimulator of liver enzymes) increases the metabolism of the propafenone. The elinical importance of this awaits assessment, but check that propafenone remains effective if phenobarbital is added, and that toxicity does not occur if it is stopped. If the suggested mechanism is correct, other barbiturates would be expected to interact similarly. 

Two isolated reports describe raised serum theophylline levels, with symptoms of toxicity, when two patients were given propafenone. 

Information is limited to these two reports, but it would seem prudent to monitor the effect of adding propafenone to established treatment with theophylline in any patient. Be alert for increased theophylline levels and signs of toxicity. Controlled studies are needed to further inveshgate this potential interaction. 

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). 

The raised desipramine levels are thought to result from decreased metabolism and clearance, caused by propafenone. The general importance of this case is uncertain, but be alert for signs of desipramine toxicity in any patient given propafenone concurrently. Adjust the desipramine dosage appropriately. 

A 17-year-old boy took propafenone 3 g and had a sudden cardiac arrest with h5fpotension, left ventricular failure, bradycardia, sinoatrial block, and an atrioventricular junctional and ventricular tachycardia. He was treated with temporary cardiac pacing, catecholamines, and sodium bicarbonate, and the toxicity resolved within 4 hours [66 ]. 

Toxicity due to propafenone at what was expected to be a therapeutic dose occurred in a 72-year-old woman who developed impaired consciousness and hypotension. She was also taking verapamil, the dose of which had recently been increased to 80 mg tds. An electrocardiogram showed atrial fibrillation... 

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