Therapeutic Levels of Intravenous Procainamide in Neonates: A Retrospective Assessment

Abstract

To evaluate dosing and pharmacokinetic parameters of intravenous continuous-infusion procainamide in neonates, and to identify dosage regimens and factors leading to therapeutic procainamide levels and minimal adverse events. Retrospective, observational study. Pediatric hospital. . Twenty-one patients (seven preterm, 14 full term) younger than 30 days who received continuous-infusion procainamide therapy for more than 15 hours or had two consecutive therapeutic procainamide levels obtained while receiving therapy between June 1, 2002, and December 31, 2005. Data on demographics, dosing, drug levels, and adverse effects were collected. Doses that achieved therapeutic levels were documented, and procainamide clearance was calculated and evaluated with regard to renal function and gestational age in patients who were at steady state. Mean clearance and mean N-acetylprocainamide (NAPA):procainamide ratios were compared between preterm and term neonates. No patients experienced hemodynamic instability or other adverse effects due to procainamide. Procainamide was given as a mean +/- SD 9.6 +/- 1.5-mg/kg bolus in 20 of 21 patients before continuous infusion. The mean +/- SD dose at which two therapeutic levels were achieved was 37.56 +/- 13.52 microg/kg/minute. Procainamide clearance was 6.36 +/- 8.85 ml/kg/minute and correlated with creatinine clearance (r=0.78, p<0.00001) and age at day of sampling (r=0.49, p<0.00001). The NAPA:procainamide ratio at steady state was 0.84 +/- 0.53; two patients were determined to be fast acetylators (ratio > 1). Preterm infants had lower mean clearance rates (p<0.001) but higher NAPA:procainamide ratios (p<0.01) than those of term infants. Five patients experienced seven supratherapeutic levels while receiving therapy; four of these patients were preterm, and all had creatinine clearances less than 30 ml/minute/1.73 m(2). Three patients had four pairs of levels obtained after discontinuation of procainamide, and elimination rate constant and half-life were calculated. Procainamide can be safely used in neonates, with no short-term adverse effects. The dosage regimen for intravenous procainamide required to achieve therapeutic levels in neonates is similar to that of older infants and children. Doses may need to be reduced in premature infants and in those with renal dysfunction.