Adverse drug reactions and off-label and unlicensed medicines in children: a nested case?control study of inpatients in a pediatric hospital

Abstract

BackgroundOff-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs.MethodsA nested case?control study was conducted within a prospective cohort study. Details of all medicines administered were recorded, including information about OLUL status. The odds ratio for OLUL medicines being implicated in a probable or definite ADR was calculated. A multivariate Cox proportional hazards regression model was fitted to the data to assess the influence that OLUL medicine use had on the hazard of an ADR occurring.ResultsA total of 10,699 medicine courses were administered to 1,388 patients. The odds ratio (OR) of an OLUL medicine being implicated in an ADR compared with an authorized medicine was 2.25 (95% confidence interval (CI) 1.95 to 2.59). Medicines licensed in children but given to a child below the minimum age or weight had the greatest odds of being implicated in an ADR (19% of courses in this category were implicated, OR 3.54 (95% CI 2.82 to 4.44). Each additional OLUL medicine given significantly increased the hazard of an ADR (hazard ratio (HR) 1.3 95% CI 1.2 to 1.3, P <0.001). Each additional authorized medicine given also significantly increased the hazard (HR 1.2 95% CI 1.2 to 1.3, P <0.001).ConclusionsOLUL medicines are more likely to be implicated in an ADR than authorized medicines. The number of medicines administered is a risk factor for ADRs highlighting the need to use the lowest number of medicines, at the lowest dose for the shortest period, with continual vigilance by prescribers, in order to reduce the risk of ADRs.

Deferred Consent for Randomized Controlled Trials in Emergency Care Settings

“…1,2 Children are not little adults, and evidence in adults cannot always be safely extrapolated to children. 3,4 This discrepancy has led to a growing recognition of the need to increase the number and quality of pediatric trials to improve the evidence base and the need for practical, appropriate, and clear information for children and families participating in studies. [5][6][7][8] In emergency pediatric settings specifically, there is a conflict between the requirement for prospective informed consent, which may not be practicable in emergencies, and the need for better evidence.…”

Relation between safe use of medicines and Clinical Pharmacy Services at Pediatric Intensive Care Units

“…The increasing number of medications being approved to adults with potential use on Pediatrics,1 the need to treat clinically challenging diseases, and the ethical issues surrounding pediatrics research put children and adolescents at more risks associated to medication adverse events 23 To illustrate this scenario, a nested-cohort study conducted by Bellis and colleagues2 demonstrated that unapproved prescriptions were associated with an augmented hazard of having an adverse event (hazard ratio 1.30, 95%CI 1.20-1.30, p <0.001).…”

“…, 3 To illustrate this scenario, a nested-cohort study conducted by Bellis and colleagues2 demonstrated that unapproved prescriptions were associated with an augmented hazard of having an adverse event (hazard ratio 1.30, 95%CI 1.20-1.30, p <0.001).…”

Off-Label Drug Use in Pediatric Practice: Unsolved Problems

“…Каждое дополнитель-ное использование ЛП в несоответствии с инструкцией влекло за собой увеличение рисков развития НР (отно-шение рисков 1,3; 95% ДИ 1,2-1,3; р < 0,001) [26]. Приведенные данные свидетельствуют об опасности подобного использования лекарственных препаратов в детской популяции.…”