(C-039) DARWIN EU® - Paracetamol overdose: a descriptive analysis of incidence rates and patient characteristics

Background: Paracetamol is one of the most common causes of drug poisoning; however, evidence regarding overdose rates and patient characteristics is limited.

Objectives: To describe incidence rates (IR) of paracetamol overdose (OD), and to characterise these patients.

Methods: Cohort study informed by 4 databases included in the DARWIN EU® data network. Databases included data from primary care (CPRD GOLD, UK), hospital data (CDWBordeaux, France), both (BIFAP, Spain) or others (UKBB, UK).

All individuals in each database at any time during 2010 to 2023 with >1 year (y) of observation were included. For characterisation, the study population was restricted to individuals diagnosed with paracetamol OD.

IR of paracetamol OD per 100,000 person-years with 95% CI were estimated overall and by age and sex. Repeated outcomes per patient were allowed using a 1-y washout. IR were not calculated in CDWBordeaux. Characteristics were assessed prior to paracetamol OD and were described based on pre-specified conditions/medications and by means of large-scale characterisation. Renal toxicity, hepatic toxicity and mortality were assessed in the month following paracetamol OD.

Results: IR of paracetamol OD per 100,000 was 2 (95CI% 2 to 2) in BIFAP, 5 (5 to 5) in CPRD GOLD and 21 (20 to 23) in UKBB. IR was higher among females and decreased with age. Individuals aged 1-17y exhibited higher IR compared to those older (IR per 100,000 in 1-17 vs. >18y: 5 [5 to 6] vs. 1 [1 to 1] in BIFAP; 8 [8 to 9] vs. 5 [4 to 5] in CPRD GOLD). Differences by sex were most pronounced among individuals aged 1-17y (IR per 100,000 in females vs. males: 8 [7 to 9] vs. 3 [2 to 3] in BIFAP; 13 [12 to 14] vs. 4 [3 to 4] in CPRD GOLD). Individuals aged 1- 17y were not included in UKBB.

We characterised 8370 patients with paracetamol OD (BIFAP: 2480, CDWBordeaux: 2125; CPRD GOLD: 3140; UKBB: 625). Individuals were more frequently female, with a median age of 21 to 57y. Most frequent history of conditions/medications were pain (17.1 to 73.5%), depressive disorders (14 to 42.4%), anxiety (9.7 to 21.0%), antidepressants (3.1 to 37.3%) and benzodiazepines (5.8 to 29.3%). Paracetamol prescriptions were recorded for 37.2% of patients in BIFAP, 7.2% in CDWBordeaux, 22.3% in CPRD GOLD, and 17.1% in UKBB in the year leading up to a month before the OD. In the month prior, corresponding figures were 16.7%, 2.1%, 12.2%, and 10.6%. Overdose in the year prior was captured in 15.7% of patients in CPRD GOLD. Following paracetamol OD, < 11% had hepatic toxicity, < 5% renal toxicity, and < 1.5% died.

Conclusions: Young females exhibited the highest IR of paracetamol OD. Mental health conditions, antidepressants, benzodiazepines and paracetamol were amongst the most recored conditions and medications prior to paracetamol OD. Hepatic toxicity occurred in < 11% of cases.