Aim-To determine the extent of use of drugs that are either not licensed (unlicensed), or are outside the terms of their product licence (oV label) in a neonatal intensive care unit. Methods-A prospective study was conducted over 13 weeks. Results-455 prescription episodes were administered to 70 babies. 63 (90%) patients were given a drug that was either unlicensed or used in an oV label way. 54.7% prescription episodes were oV label, many for more than one reason, and 9.9% (45) were unlicensed; 35.4% (161) prescription episodes were licensed. Conclusion-The use of unlicensed and off label drugs in neonatal intensive care seems to be far greater than other paediatric settings. This highlights the difficulties faced by those trying to ensure safe and eVective prescribing for neonates. Urgent action is required to resolve this situation.

Objective: To determine the extent of use in children in hospital of drugs that are not specifically licensed for use in children (unlicensed) and of drugs that are used outside the terms of their product licence that apply to indication, age, dose, or route of administration (off label). Design: Prospective study of drugs administered on paediatric medical and surgical wards for 13 weeks. Setting: Regional children's hospital. Subjects: Paediatric inpatients in medical and surgical wards. Main outcome measures:Comparison of the use of each drug with its product licence to determine whether the drug was used in an unlicensed or off label manner. Results: 2013 courses of drugs were administered to 609 paediatric patients in 707 admissions. 506 (25%) of the drug courses (prescriptions) were either unlicensed (139) or off label (367) uses. In 256 (36%) of the 707 admissions patients received one or more courses of an unlicensed or off label treatment in hospital. Conclusions: Use of drugs in an off label or unlicensed manner to treat children is widespread. Drugs are more likely to be used in an off label manner than in an unlicensed manner.

The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.

BackgroundLong courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels.MethodsA literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included.ResultsOne hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths).ConclusionsWeight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.

Fifty-three critically ill infants and children received midazolam as sedation in a regional intensive care unit. Assessment of the level of sedation was carried out at regular intervals on withdrawal of midazolam. Forty-nine patients were fully alert within 4 h of midazolam being stopped. Four patients took from 6 h to 1 week to become fully alert. Four patients had abnormal behaviour highly suggestive of midazolam withdrawal. The onset of abnormal behaviour was within 12 h of discontinuation of midazolam. The duration of the abnormal behaviour ranged from 3 h to 1 week. One child had a paradoxical reaction to midazolam. The overall incidence of adverse effects to midazolam in the patients studied was 17%. No adverse effects were observed in infants; all adverse effects were observed in children. We have shown that it is possible to prospectively study the toxicity of sedatives in critically ill infants and children.

BackgroundShort-course oral corticosteroids are commonly used in children but are known to be associated with adverse drug reactions (ADRs). This review aimed to identify the most common and serious ADRs and to determine their relative risk levels.MethodsA literature search of EMBASE, MEDLINE, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions to identify studies in which oral corticosteroids were administered to patients aged 28 days to 18 years of age for up to and including 14 days of treatment. Each database was searched from their earliest dates to December 2013. All studies providing clear information on ADRs were included.ResultsThirty-eight studies including 22 randomised controlled trials (RCTs) met the inclusion criteria. The studies involved a total of 3200 children in whom 850 ADRs were reported. The three most frequent ADRs were vomiting, behavioural changes and sleep disturbance, with respective incidence rates of 5.4%, 4.7% and 4.3% of patients assessed for these ADRs. Infection was one of the most serious ADRs; one child died after contracting varicella zoster. When measured, 144 of 369 patients showed increased blood pressure; 21 of 75 patients showed weight gain; and biochemical hypothalamic–pituitary–adrenal axis suppression was detected in 43 of 53 patients.ConclusionsVomiting, behavioural changes and sleep disturbance were the most frequent ADRs seen when short-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.Trial registration numberCRD42014008774. By PROSPERO International prospective register of systematic reviews.

ObjectivesTo prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour.SettingA single centre prospective observational study.ParticipantsChildren (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit.Primary and secondary outcomesPrimary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes.Results180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR.ConclusionsBehavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children.Trail registration numberEudraCT (2007-000565-37).

Aim: Appropriate formulations are essential in pharmacotherapy. This study surveyed the use of different formulations by children in the community, and examined the reported lack of appropriate formulations (oral solutions) in relation to the licensing status of drugs. Methods: A crosssectional study based on 68 019 pharmacy dispensing records was performed in The Netherlands. For each prescription the formulation was assessed, and all prescriptions were categorized: unlicensed (no product licence), off‐label (licensed drugs used outside the licence terms) and authorized (licensed drugs used according to the licence). The types of formulation used were assessed in relation to age and licensing status. Results: In all age groups, approximately half of all prescriptions were for oral drugs. The only major age‐related trend was within oral drugs: younger children were more likely to be prescribed oral solutions. For authorized drugs the proportion of tablet/capsules exceeded oral solutions at the age of 7 y, whereas for off‐label drugs this occurred at 3 y of age. For those medicines prepared by the pharmacy, tablets and capsules were more likely to be prescribed from the age of 9 y. Conclusion: Many children in the community receive inappropriate oral formulations. Regulatory authorities and the pharmaceutical industry need to ensure that children have access to medicines with appropriate formulations.