Unapproved Prescriptions in Two Pediatric Intensive Care Units in Israel

Background: Many medications prescribed to children worldwide have not been approved for pediatric use because the necessary clinical trials have not yet been performed. Children given these drugs have been shown to be at increased risk for adverse drug reactions. Objective: The aim of this study was to assess the extent of unapproved (off label and/or unlicensed) use of medications in pediatric intensive care units (PICUs) in Israel. Methods: Medications administered to patients treated in the PICUs of Soroka University Medical Center (SMC) and Assaf Harofe Medical Center (AHMC) were reviewed. Analyses were retrospective at SMC and prospective at AHMC. Results: The records of 158 patients were included in the study - 116 patients at SMC (73. 4%; 62 boys, 54 girls; mean [SD] age, 38.9 [50.4] months) and 42 at AHMC (26. 6%; 26 boys, 16 girls; mean [SD] age, 63.3 [69.3] months). They received a total of 123 different medications. Sedatives and antibiotics were the most frequently prescribed drug classes at SMC (15.2% and 6.5%, respectively), and antibiotics, acetaminophen, and antiasthmatic drugs were most frequently prescribed at AHMC (14.4%, 13.6%, and 6.8%, respectively). Sympathomimetic drugs, sedatives, and antibiotics were the drugs most commonly prescribed in an unlicensed or off-label manner at SMC (11.4%, 11.4%, and 6.5%, respectively); at AHMC, they were antiinfectives, sympathomimetics, antiasthmatic drugs, and acetaminophen (18.7%, 16.9%, 12.7%, 6.8%, respectively). The percentage of patients receiving unapproved medications (SMC, 93 [80.2%]; AHMC, 38 [90.5%]) and the percentage of unlicensed and off-label prescriptions (SMC, 243 [41.5%]; AHMC, 118 [41.0%], respectively) were similar between the 2 PICUs. Inappropriate age was the most common off-label category, followed by different dose, different indication, and different route. Conclusion: The results of this study of unapproved prescriptions in 2 PICUs in Israel show a high number of such prescriptions and indicate an urgent need to investigate the use of those medications in children.