Should pharmacotherapy of digoxin be reviewed in male patients with heart failure in the case of association with carvedilol?

Abstract

Digoxin is an inotropic agent currently prescribed at a daily dose of 0.125 or 0.25 mg orally [1]. Due to its narrow therapeutic range (0.8 to 2.0 ng/mL), intoxication may occur due to drug interactions or health status that change digoxin pharmacokinetic parameters [2]. The pharmacotherapy with this digitalis often requires constant monitoring of its plasma concentration (Cp) being intoxication avoided by the adjustment of digoxin therapeutic regimen [2]. So it can be considered safe and well tolerated when dosed appropriately [3].It is important to highlight that digoxin is inexpensive and then can be afforded by most patients with heart failure throughout the world [3]. According to Gheorghiade et al. digoxin reduces hospitalizations in patients with chronic heart failure and, when combined with β-blockers, it remains a useful agent to achieve rate control in atrial fibrillation [3].Several major trials have established the cardiovascular benefits of carvedilol over traditional non-vasodilating β-blockers in patients with heart failure [4] and this drug is currently used, as well as digoxin, in the pharmacotherapy of heart failure with systolic dysfunction [1].According to Wermeling et al. carvedilol increased digoxin's oral bioavailability (0.25 mg dosage) as well as renal elimination in twelve patients with mild to moderate hypertension after 2 weeks of concurrent treatment [5]. However, the absolute change in digoxin pharmacokinetics was small and considered not clinically significant [5]. In a crossover study with eight healthy male subjects aged between 23 and 27 years, 25 mg carvedilol increased the mean maximum plasma concentration and the area under the plasma concentration time curve of digoxin just when administered orally (single dose of 0.5 mg) [6].Grunden et al. performed a prospective, double-blind, placebocontrolled trial with twenty-two New York Heart Association functional class II-III patients with idiopathic dilated cardiomyopathy selected from a clinical trial evaluating the efficacy and hemodynamic effects of chronic carvedilol treatment in heart failure [7]. Clinical significant changes in serum digoxin concentrations were not observed in most patients who receive carvedilol concomitantly. Additionally, no patients required digoxin dosage adjustments and there were no clinically significant adverse events directly attributable to an increase of serum digoxin concentration [7].Digoxin is also often coadministered with carvedilol in children with severe ventricular failure [8]. Ratnapalan et al. showed that in eight children (age 2 weeks to 8 years), the oral clearance of digoxin was decreased by half with carvedilol (dose range between 0.08 and 1.06 mg/kg/day); this β-blocker increased serum concentrations of digoxin in children and two of them had digoxin toxicity [8].A crossover study including twenty-four patients (12 males and 12 females, mean patient age 67.8 ± 8.2 years) with New York Heart Association class II-III heart failure was conducted by Baris et al. to evaluate the influence...

Spontaneous and Isoprenaline-evoked response of isolated heart preparations from rats submitted to leptin treatment during lactation

“…As the ability of sympathetic nervous system to maintain cardiac function decreases in the course of chronic heart failure, sympathomimetics used as positive inotropes for acute heart failure significantly increase mortality if used chronically [8]. Several major trials have established the cardiovascular benefits of carvedilol, a β-blocker, in patients with heart failure and this drug is currently used in the pharmacotherapy of heart failure with systolic dysfunction [10].…”