Physiological changes during development of neonates, infants and children affect pharmacokinetic and pharmacodynamic properties of many drugs. The immaturity of the organism and its considerable changes over time strongly affect absorption, distribution, biotransformation and excretion of drugs, and thus their efficacy and safety. Children, particularly under 4 years of age, are susceptible to a range of adverse effects observed in adults, but they can also develop additional reactions due to direct drug toxicity on the developing organs. However, only scarce evidence exists on the action of drugs in children since most pharmacokinetic and pharmacodynamic studies have been conducted in adults. In the United States and European Union, also in Poland, off-label and unlicensed use of drugs are allowed and commonly practised, mainly in hospitalised children. This means that a drug can be used in a different way than described in the Summary of Product Characteristics, e.g. doses or intervals between them can be changed, the drug can be used for different indications, the route of administration or age range can be different, etc. The rationale underlying such actions is the necessity of saving life or health or inefficacy of previous treatment. It is estimated that 25–89% of hospitalised children and 69–100% of newborns treated in neonatal intensive care units worldwide have received at least one drug in the off-label manner or as an unlicensed product. Studies and reports on pharmacovigilance have shown that adverse drug reactions in children after off-label use are an important problem. As a response to such signals, the European Medicines Agency issued certain legislative changes in 2007 to enable clinical trials in children and to develop paediatric formulations of drugs, particularly for neonates. The article discusses age-related differences in absorption, distribution, biotransformation and excretion of drugs depending on the route of administration as well as problems associated with off-label and unlicensed use of drugs and adverse effects of drugs in children.

infant, developmental differences, pharmacokinetics, off-label and unlicensed drug use, adverse effects