Propafenone with digoxin

Concurrent administration of propafenone with digoxin, warfarin, propranolol, or metoprolol increases the serum concentrations of the latter four drugs. Cimetidine slightly increases the propafenone serum concentrations. Additive pharmacological effects can occur when lidocaine, procainamide, and quinidine are combined with propafenone. 

A placebo-controUed study of the use of propafenone 450-600 mg orally, either alone or in combination with digoxin, has been carried out in 176 patients with atrial fibrillation a further 70 patients were given digitalis plus quinidine (12). There were no significant differences across the groups in terms of percentage conversion to sinus rhjThm,... 

Bianconi L, Mennuni M. Comparison between propafenone and digoxin administered intravenously to patients with acute atrial fibrillation. PAFIT-3 Investigators. The Propafenone in Atrial Fibrillation Italian Trial. Am J Cardiol 1998 82(5) 584-8. 

Not understood. One suggestion is that propafenone inereases the bioavailability of the digoxin. Another is that the volume of distribution and non-renai clearance of digoxin are ehanged by the propafenone. Conversely, others reported that propafenone decreased the renal clearance of digoxin. There is certainly some in vitro evidence that propafenone and its metabolite inhibit the P-glyeoprotein transporter, which is concerned with digoxin secretion by the rend tubular cells. ... 

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). 

Propafenone causes a small increase in plasma digoxin concentrations by an unknown mechanism (277,278). Although this effect is perhaps not clinically significant, in patients with dysrhjhhmias it was accompanied by an increase in PR interval (214). 

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