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Incidence and predisposing factors for flucloxacillin-related hepatotoxicity in children
Stefan Coombs1, Laure F Pittet2,3,4, Kailey Tang4
1Department of Pharmacy and General Medicine, The Royal Children's Hospital Melbourne, 50 Flemington Road Parkville, Victoria 3052, Australia.
Insights
Flucloxacillin can cause liver damage in children, with 17% incidence in this study. Older children and those on multiple medications face higher risks of flucloxacillin-induced hepatotoxicity.
Area of Science:
- Pediatric Pharmacology
- Hepatology
- Adverse Drug Reactions
Background:
- Flucloxacillin-induced hepatotoxicity is recognized in adults but less studied in children.
- This antibiotic is frequently prescribed to pediatric patients.
- Limited pediatric data necessitates investigation into flucloxacillin's liver effects in children.
Purpose of the Study:
- To determine the incidence of flucloxacillin-induced hepatotoxicity in pediatric patients receiving intravenous therapy.
- To identify risk factors associated with flucloxacillin-induced liver injury in children.
- To evaluate the severity and time course of this adverse drug reaction.
Main Methods:
- A retrospective audit of children (0-18 years) receiving IV flucloxacillin for ≥24 hours was conducted over two years.
- Liver function tests were analyzed before and after antibiotic administration.
- Causality was assessed using established methods like Roussel Uclaf Causality Assessment Method and Naranjo criteria.
Main Results:
- The incidence of flucloxacillin-induced hepatotoxicity was 17% (66/393 children).
- Older age (especially 12-18 years) and concomitant use of multiple hepatotoxic medications were significant risk factors.
- Severe liver injury occurred in 14-20% of affected children, with a median onset of 4 days and resolution in 5 days.
Conclusions:
- Older children and those on multiple hepatotoxic drugs are at increased risk for flucloxacillin-induced liver injury.
- The findings highlight the importance of monitoring liver function in pediatric patients receiving flucloxacillin.
- Further research may inform safer prescribing practices for this common antibiotic in children.
Background:
Flucloxacillin-induced hepatotoxicity is well established in adults. However, there are few paediatric studies of flucloxacillin-induced hepatotoxicity despite this drug being among the most commonly prescribed in children. We aimed to determine the incidence of flucloxacillin-induced hepatotoxicity in children receiving IV therapy as well as identify risk factors for this adverse drug reaction.
Methods:
We undertook a 2 year retrospective audit of children aged 0-18 years admitted to the Royal Children's Hospital (March 2019 to March 2021) who had liver function tests determined before and after receiving IV flucloxacillin for at least 24 hours duration. Causality was assessed using the Roussel Uclaf Causality Assessment Method and Naranjo criteria.
Results:
Overall, the incidence of hepatotoxicity was 66/393 (17%). The median age of children with hepatotoxicity was 1.1 years (IQR 0.3-11.9), 43 (65%) received two or more concomitant hepatotoxic medications and 23 (35%) were receiving total parenteral nutrition. The median timing of onset of hepatotoxicity after commencement of flucloxacillin was 4 days (range 2-7). Severe hepatotoxicity (Common Terminology Criteria for Adverse Events grade 3 or above) occurred in 9/66 (14%) for bilirubin, 13/66 (20%) for ALT and 10/66 (15%) for GGT. Predisposing factors for hepatotoxicity were increasing age (OR 1.06 per additional year, 95% CI 1.01-1.10, P = 0.02), with adolescents aged 12-18 years having the highest risk (OR 5.10, 95% CI 2.02-12.85, P = 0.001), and two or more concomitant hepatotoxic medications (OR 2.51, 95% CI 1.02-6.18, P = 0.05). The median time to resolution of hepatotoxicity after cessation of flucloxacillin was 5 days (range 2-10).
Conclusions:
In children, older patients and those receiving two or more concomitant hepatotoxic medications are at greater risk of flucloxacillin-induced hepatotoxicity.
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