Off-label drug use and adverse drug events (ades) in paediatric patients: an analysis of the jordanian national pharmacovigilance database

S. A. Al-Zubiedi1, N. Bawaresh2. 1Biopharmaceutics & Clinical Pharmacy, The University of Jordan, Amman, JORDAN, 2Rational Drug Use (RDU) Department, Jordan Food and Drug Administration (FDA), Amman, JORDAN

Introduction: Off-label drug use in pediatrics is common due to lack of pediatrics clinical trial and safety testing. Although, it provides the best available treatment for pediatrics where drugs have not been evaluated for their safety, drug administration outside the conditions assessed during clinical trials may result in significant consequences i.e. adverse drug events (ADEs) (1). The aim of this study was to assess the impact of off-label drug use on ADEs in paediatric patients using the Jordanian National Pharmacovigilance Database.

Method: All spontaneous reports of ADEs in paediatrics patients (i.e. age < 18 years) recorded in the National Jordanian Pharmacovigilance Programme Database between January 2013 and December 2015 were investigated. Reports with missing age or event details were excluded. All reports included were assessed in order to define each primary and secondary suspected drug as either authorized, off-label, or unknown. Off-label was defined as the use of a drug outside the terms of the drug labeling/licensing (2). In the current analysis, an adverse event was considered serious if it resulted in inpatient hospitalization or prolongation of existing hospitalization.

Results: Between January 2013 and December 2015, 845 valid ADEs in paediatrics were reported to the Jordanian Pharmacovigilance Program. Overall, off-label drug use was responsible for 74% of the reported ADEs in paediatrics. Upon evaluation of the categories of off-label use, 95% was attributed to a non-indicated use. Of all off-label ADEs, anticancer (84%), immunosuppressant (63%), and antimicrobial (36%) were the most commonly implicated classes of medications. Off-label ADEs were significantly more frequent in infants (90%) than in any other age categories (P=0.002). Total of 256 (30%) of the reported ADEs were serious i.e. resulted in hospital admissions. ADEs associated with off-label prescription were more likely to be implicated in hospital admissions than authorized drugs (RR 1.56, 95% CI 1.18, 2.06, P < 0.001). After excluding oncological drugs, off-label ADEs did not significantly increase the risk of hospitalization .

Conclusion: off-label drug use is more likely to be implicated in an ADEs than authorized medicines in pediatrics. Overall, off-label drug use in pediatrics is associated with increased risk of hospitalization. Our study highlights the needs to improve the study of drug safety in the pediatric population.

References: (1) Turner S et al. (1999) Acta Paediatr 88: 965-968. (2) Bellis JR et al. (2014) Br J Clin Pharmacol; 77: 545-553.