Objective To describe the use of medicines and to determine the frequency of off-label use in emergency room paediatric patients. Patients and methods A prospective, observational and descriptive study was carried out in the setting of the paediatric emergency room of a Spanish general hospital. Medicines used by children <14 years prior to their emergency room visit were analysed based on information collected from parents/guardians and relatives for each drug prescription. Off-label use was defined as the utilization of a drug at an indication, dosage, frequency or route of administration that differed from the specifications in the Summary of Product Characteristics or by children outside the authorized age group. Results The patient cohort comprised 462 children, among whom 336 children had been prescribed 667 prescriptions. Of the medicines prescribed, 90% fell into only five 5 Anatomical Therapeutic Chemical Classification System groups. The most frequent active principles were ibuprofen and paracetamol. Of a total of 152 different formulations recorded, no paediatric information was provided for 40 formulations, and one formulation was contraindicated in children. Based on the established criteria, 338 prescriptions were off-label: no paediatric information or contraindication in children were available (82 prescriptions); the drug was used for an indication different from the authorized one (111 prescriptions); drug use was inconsistent with age recommendations (16 prescriptions); drug use was inconsistent with dose/frequency (129 prescriptions). Of the 152 formulations, 107 were occasionally used in an off-label manner. Conclusions Although the mean number of drugs used in children is small, off-label use is frequent. Research efforts should target paediatric studies that allow a rational drug use in children.

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Randomized controlled clinical trials are felt by the medical community to provide the best evidence. Participation in trials involves the possibility of obtaining benefits but also of suffering some risks. Those risks are often considered unacceptable for children but if clinical trials are not conducted in children, clinicians are forced to extrapolate study data from adults. In 1968 H. Shirkey termed children "therapeutic orphans" because of the lack of adequately tested and labeled drugs available in appropriate formulations. Research involving children entails specific difficulties as the need to study children of different ages, the small number of children affected by certain diseases or ethical issues. This paper considers aspects of pediatric clinical pharmacology and children's responses to drugs. It also reviews some of the current situations in pediatric clinical trials, covering aspects such as: the benefits and risks of trial participation; the specificity of pediatric trial design; the ethical issues such as consent; the use of placebo or the participation of healthy children; and the current legal situation in Europe and in the USA.

Inappropriate use or unintentional ingestion of naphazoline, especially in children, can quickly cause severe central nervous system depression and cardiovascular adverse effects [2,6].A five-year-old boy arrived at the Emergency Room 90 min after the ingestion of approximately 10 ml of Euboral Oftálmico solution (9.7 g of sodium-tetraborate, 0.1 g of naphazoline-chlorhydrate and 0.2 g of methylparaben for 1 l dilution, for topical use), prepared in a bottle without a label in a 0.02% concentration, which was twice that of the manufacturer's recommendation. During the physical examination, bradycardia (heart rate 45-50 bpm), hypothermia (35.5°C) and a blood pressure of 100/ 70 mmHg (blood pressure percentile 75th/90th) were observed. Gastric lavage and activated carbon administration were performed. A few minutes later, the patient presented somnolence, sweating, persistence of the bradycardia and hypothermia. Blood pressure and oxygen saturation were normal. At the EKG (electrocardiogram), sinusal bradycardia of 48 bpm was observed and laboratory parameters showed no abnormalities. Blood analysis of standard toxicological drugs was performed with negative results.Infusion therapy was started to force diuresis and the patient was admitted to the hospital in order to monitor vital parameters. Bradycardia lowest value (47 bpm) was observed 3 h after the ingestion. Somnolence and hypothermia (35.2°C) were maximum 7 h after the ingestion and sweating persisted until 12 h later. Blood pressure also returned to normal during this period without treatment; its highest value was 130/80 mmHg (blood pressure percentile >99th/99th) with no subsequent hypotension. The patient was discharged 20 h later.Naphazoline has a narrow therapeutic to toxic window and intoxication may occur at a dose of 0.05 mg/kg body weight [2]. Systemic side effects are observed rarely, despite frequent and uncontrolled use because of partial availability without doctor's prescription. They can progress potentially up to intoxication with vitally threatening cardiovascular symptoms (arterial hypertension with reflex bradycardia defined as a heart rate under 60 bpm and possible ischaemia of vital functions), pulmonary and central nervous symptoms. The central nervous system effects concern the reduction of vigilance ranging from drowsiness to coma, persisting cardiovascular hypotension and reduced respiration rate up to the Cheyne-Stokes breathing and possible pulmonary edema, hypothermia, mydriasis, hyperhydrosis and transient excitation hyperreflexia [1]. Our patient presented a large number of the symptoms described above, especially those affecting cardiovascular and central nervous systems. Blood analysis of standard toxicological drugs excluded alternative causes of intoxication.Because of rapid absorption, we wonder whether gastric lavage and carbon-activated administration are the suitable Eur J Pediatr (2006) 165:815-816