Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to a paediatric hospital

TLDR

To examine the impact of off‑label and unlicensed prescribing on adverse drug reactions causing unplanned admissions to a paediatric hospital. The study used a 12‑month prospective cohort of paediatric admissions, calculating relative risks and performing logistic regression to assess the association between off‑label/unlicensed medicines and ADRs. Off‑label and unlicensed medicines were linked to a 67 % higher ADR risk, with each additional off‑label/unlicensed course raising risk by 23 % and each authorized medicine by 25 %, though in non‑oncology patients only authorized medicines predicted ADRs, indicating oncology drugs largely drove the increased risk.

Abstract

To examine the impact of off-label and unlicensed (OLUL) prescribing on adverse drug reactions (ADRs) causing unplanned admissions to a paediatric hospital.Prescription data from a 12 month prospective cohort study of ADRs detected in children admitted to a paediatric hospital were scrutinized. The relative risk for off-label and unlicensed medicines being implicated in an ADR was calculated. Logistic regression analyses were carried out with exposure to off-label and unlicensed medicines and number of off-label and unlicensed medicines administered as predictor variables.Off-label and unlicensed medicines were more likely to be implicated in an ADR than authorized medicines (relative risk 1.67, 95% CI 1.38, 2.02, P < 0.001). There was a 25% increase in ADR risk (95% CI 1.16, 1.35, P < 0.001) with each additional authorized medicine and 23% (95% CI 1.10, 1.36, P < 0.001) with each additional off-label or unlicensed medicine. Logistic regression analysis focusing on non-oncology patients demonstrated that the number of authorized medicines (odds ratio 1.33, 95% CI 1.23, 1.44, P < 0.001), but not the number of off-label and unlicensed medicine courses, was a predictor of ADR risk.In a heterogeneous population of children admitted to a secondary/tertiary hospital, off-label and unlicensed medicines are more likely to be implicated in an ADR than authorized medicines. This was largely driven by ADRs related to drugs used in oncological practice, where the usage of off-label or unlicensed medicines was associated with a higher ADR risk than in non-oncological areas.