DARWIN EU® – Paracetamol prescribing and paracetamol overdose in Europe: a descriptive analysis of trends and patient characteristics

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  PARACETAMOL
• Anatomical Therapeutic Chemical (ATC) code:
  (N02BE01) paracetamol

  paracetamol

Population studied

• Short description of the study population:
  For objective 1 and 2, the study population will comprise all individuals present in the database at any time from 1st January 2010 to 31st of December 2023 (or the latest year with complete observation). For objective 3, the study will comprise of individuals with paracetamol overdose for the first time in their patient history during the study period.; ; For incidence calculations (objective 1 and 2), individuals with a record of the outcome will re-enter the study after a certain amount of time (i.e. washout period) so further occurrences of the outcome can be captured. This washout period will be defined as 60 days following the end of the prescribed treatment for paracetamol prescribing and 365 days for paracetamol overdose. For objective 3, individuals with a prior history of paracetamol overdose any time prior to index date will be excluded. ; ; A year of observation history prior to index date will be required for all individuals within selected databases except CDWBordeaux. Individuals aged less than 1 year of observation history will be excluded.

Study design details

• Study design:
  1. Population-level drug utilisation study to assess incidence and prevalence of paracetamol prescribing (objective 1) 2. Population-level descriptive epidemiology study to estimate the incidence of paracetamol overdose (objective 2) ; 3. Patient-level characterisation study
• Main study objective:
  The aim of the study is to provide an overview of paracetamol prescribing and paracetamol overdose trends in selected European databases, and to characterise patients presenting with paracetamol overdose. ; ; The specific objectives of the study are: ; 1. To examine the incidence/prevalence of paracetamol prescribing (overall, and by age, sex, formulation and country/database). ; 2. To examine the incidence of paracetamol overdose (overall, and by age, sex, country/database). ; 3. To characterise patients with paracetamol overdose, in terms of comorbidities, co-prescribed medications, prior paracetamol prescription, and incidence of short-term complications and mortality.
• Setting:
  This study will be conducted using routinely collected data from 8 databases in 7 European countries selected from the DARWIN EU® Database Catalogue. All databases were previously mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM).
• Outcomes:
  Outcomes included paracetamol prescribing and paracetamol overdose (Table 6). The use of paracetamol ; was derived from prescription data.
• Summary results:
  CONCLUSION ; Incidence rates and prevalence of paracetamol prescribing differed by data source. Incidence rates per 100,000 ranged between 1,578 to 12,686, and prevalence from 5.2% to 65.1%. In general, figures of paracetamol prescribing were higher among females than males and increased with age. When stratified by formulation, oral tablet formulations had the highest estimates, while injectable liquid formulations were generally the least prescribed. Oral liquid formulations and rectal suppositories were more frequently prescribed among individuals aged 1 to 5 years. ; Incidence of paracetamol overdose per 100,000 was 2 (2 to 2) in BIFAP, 5 (5 to 5) in CPRD GOLD and 21 (20 ; to 23) in UKBB, which was lower than expected based upon published literature. Where available, rates among individuals aged 1 to 17 years were higher than those aged 18 or older. This gap was particularly pronounced among females and appeared to have widened after 2020. ; Individuals with paracetamol overdose were more frequently female, with a median age of 21 to 25 years (in databases with all ages captured). Most frequent pre-specified conditions considering all prior history were pain, depressive disorder, anxiety disorders, and arthrosis/arthritis, while the most frequent medications in the month prior were paracetamol, antidepressants, and benzodiazepines. Records of suicidal thoughts, poisoning by psychotropic agents, overdose or self-inflected injuries prior to paracetamol overdose were also captured. In the month following the paracetamol overdose, hepatic toxicity was observed in less than 11% of cases, renal toxicity was found in less than 5% of patients, and mortality in less than 1.5% of cases.