Allergic Reactions Associated with Intravenous Versus Intramuscular Pegaspargase: A Retrospective Chart Review.

BACKGROUND: Pegaspargase (PEG-ASP) is essential chemotherapy for acute lymphoblastic leukemia (ALL). Since changing to intravenous (IV) administration from intramuscular (IM), an increased number of allergic reactions have been anecdotally noted at our institution. This study compares the rate and severity of allergic reactions in children receiving IM or IV PEG-ASP. METHODS: We performed a retrospective chart review of patients treated with IV or IM PEG-ASP at The Hospital for Sick Children, Toronto, Canada, from March 1, 2010 to January 1, 2012. The incidence and severity of allergic reactions attributed to PEG-ASP were documented. Patient age, sex, route of PEG-ASP administration, disease (risk group and lineage) and mean time interval between PEG-ASP doses were evaluated as possible risk factors for allergic reaction. RESULTS: A total of 109 patients were included. There were 14 (35 %) allergic reactions among 40 patients who received IV, compared with eight (12 %) of the 69 who received IM [odds ratio (OR) 4.11, 95 % confidence interval (CI) 1.54-10.97, p = 0.005]. In multivariable logistic regression adjusting for disease risk group, route (IV vs. IM) remained independently significant (p = 0.011). Patients with standard-risk ALL had a lower risk of experiencing an allergic reaction associated with PEG-ASP compared with patients in high-risk disease risk groups (collectively referred to as "other"; 11 vs. 31 %, OR 3.36, 95 % CI 1.16-9.72, p = 0.025). CONCLUSIONS: IV PEG-ASP is associated with a significantly higher rate of allergic reactions than IM. The clinical preference for IV PEG-ASP may warrant re-evaluation.

Dose derivation of once-daily dosing guidelines for gentamicin in critically ill pediatric patients.

OBJECTIVES: To determine dose and eligibility criteria for once-daily dosing (ODD) of gentamicin in critically ill pediatric patients. METHODS: Retrospective chart review of patients admitted to the Pediatric Intensive Care Unit or Cardiac Critical Care Unit at The Hospital for Sick Children (SickKids) who received traditionally dosed intravenous (IV) gentamicin (January 2008 to June 2010). Statistically significant patient characteristics associated with gentamicin pharmacokinetic (PK) parameters were determined by multiple linear regression. Binary partitioning was used to set critical values for these characteristics to derive dose for ODD of gentamicin. Feasibility of implementing ODD of gentamicin in critically ill children was assessed using individualized PK parameters to simulate area under the concentration-time curves and drug-free intervals while targeting a maximum concentration (C(max)) of 16-20 mg/L. Eligibility criteria were determined by patient characteristics that had a statistically significant impact on gentamicin PK. RESULTS: Volume of distribution (V(d)) and elimination rate constant (k(e)) were calculated for 140 patients. Weight and admission unit were significantly associated with weight-normalized V(d) (Vd/kg), whereas age and serum creatinine (SCr) were significantly associated with k(e). Weight <5 kg and SCr ≥20% over age-specific upper normal limit before gentamicin initiation were associated with prolonged gentamicin elimination. Gentamicin 6 mg/kg IV every 24 hours, the dose at which the highest percentage of patients achieved C(max), area under the curve, and drug-free interval within target ranges simultaneously, was selected as the proposed ODD regimen. CONCLUSIONS: A regimen of gentamicin 6 mg/kg IV every 24 hours for Pediatric Intensive Care Unit/Cardiac Critical Care Unit patients at SickKids weighing ≥5 kg with SCr <20% above age-specific upper normal limit before initiation of gentamicin is proposed.