An Assessment of Pyrexia, Patient Age and Weight; Pediatric Considerations.

Abstract

Sterile drug products' endotoxin specifications are set in accordance with a compendial method that considers a patient population's body weight and the threshold pyrogenic dose for the particular route of administration (e.g., parenterally, subcutaneously, intrathecally). These specifications are designed to prevent pyrexia (fever) from occurring. For intravenously derived products, the threshold pyrogenic dose is 5 EU per kg body weight. All clinical studies supporting the pyrogenic dose have only incorporated adult (>18 years) recipients of intravenous standard endotoxin. These studies have not considered the potential for children to respond differently to administered endotoxins. Here, an evaluation is reported using patient fever data from the FDA Adverse Events Reporting System (FAERS) to assess potential child patient age (<1 to 18 years) and body weight implications to parenteral product endotoxin specifications. Data indicate that the response to endotoxin by children is not uniform across the body weight range of individual age groups (<1, 1-2, 3-4 years, etc.). Furthermore, that children <3-4 years of age appear more prone to pyrexia. Notwithstanding the inherent limitations and caveats in this study, the sum aggregate of information suggests the necessary adoption of worst case (5^th percentile of population body masses) for children aged <3-4 years.