Safety and Biopharmaceutical Challenges of Excipients in Off-Label Pediatric Formulations

BACKGROUND: One of the major challenges in pediatric treatment is the lack of suitable drug preparations specifically designed and marketed for children. Most of the FDA approved drug formulations for adults have not been approved for use in pediatric patients. Shortage of suitable pediatric dosage information often leads health professionals to use adult formulations in an off-label manner. The aim of this work was to review the safety and biopharmaceutical challenges of commonly found excipients in off-label pediatric formulations as well as to show the current progress to alleviate pediatric toxicity related to excipients. METHODS: Research findings and medical case reports were searched from credible sources including Scopus, PubMed, OVID, Google Scholar, Embase, Cochrane Library, and Web of Science. RESULTS: As several studies and clinical case reports have revealed, off-label adult formulations usage causes pediatric patients to become exposed to potentially harmful excipients, which are essential components of drug products. In addition to their toxicities, some of the excipients affect the biopharmaceutical property of different drugs. Immature organ and body composition, large body surface area and slower metabolism and elimination capabilities of pediatrics are the main causes of toxicities associated with different excipients. Recent studies have also shown that good progress is being made to develop safe and suitable excipients for pediatric use. CONCLUSION: A risk and benefit assessment should be done before using off-label formulation as excipients cause mild to severe toxicities and biopharmaceutical problems to pediatric patients.