Off-label and unlicensed use of antidotes in paediatric patients

Objective: To determine the extent of unlicensed and off-label antidotes among medicines recommended by the International Programme on Chemical Safety (IPCS) for children. Materials and methods: We considered 77 antidotes from the "IPCS List of antidotes and other useful agents in the treatment of human poisoning" (1996 version). Primary reference sources used were the Physicians' Desk Reference (PDR) and package inserts. Antidotes were assessed for off-label (outside of the term of product license) and unlicensed use in children. Results: Our data show that only 31 (40.3%) of 77 recommended antidotes correspond to the demands of licensing systems for use in children. The rest (46 or 59.7%) are either off-label (32 or 41.5%) or unlicensed (14 or 18.2%). Five antidotes are off-label for two reasons; thus the total number of off-label use (37) is greater than the number of such drugs (32). Inappropriate age is the main reason for use outside the stipulations of the product license (24 of 77 antidotes or 31.2%), whereas different indication and route occur in 11 (14.3%) and 2 (2.6%) antidotes, respectively. The 14 unlicensed antidotes have been used only in animal experiments or in a small number of patients in certain poison centres. Conclusions: Sixty percent of antidotes and other useful agents in the poison treatment of children do not correspond to the demands of licensing systems. Drugs used in the treatment of poisoned children, as well as adults, must be evaluated scientifically.