Drug Utilisation Patterns of Alternatives to Ranitidine-Containing Medicines in Patients Treated with Ranitidine: A Network Analysis of Data from Six European National Databases

Drug Saf. 2023 Dec;46(12):1353-1362. doi: 10.1007/s40264-023-01354-9. Epub 2023 Oct 31.

Abstract

Introduction: Ranitidine, a histamine H2-receptor antagonist (H2RA), is indicated in the management of gastric acid-related disorders. In 2020, the European Medicines Agency (EMA) recommended suspension of all ranitidine-containing medicines in the European Union (EU) due to the presence of N-nitrosodimethylamine (NDMA) impurities, which were considered to be carcinogenic. The aim of this study was to investigate the impact of regulatory intervention on use patterns of ranitidine-containing medicines and their therapeutic alternatives.

Objectives: The aim was to study drug utilisation patterns of ranitidine and report discernible trends in treatment discontinuation and switching to alternative medications.

Methods: This retrospective, population-based cohort study was conducted using primary care records from six European countries between 2017 and 2023. To explore drug utilisation patterns, we calculated (1) incident use of ranitidine, other H2RAs, and other alternative drugs for the treatment of gastric ulcer and/or gastric bleeding; (2) ranitidine discontinuation; and (3) switching from ranitidine to alternative drugs (H2RAs, proton-pump inhibitors [PPIs], and other medicinal products for acid-related disorders).

Results: During the study period, 385,273 new ranitidine users were observed, with most users being female and aged 18-74 years. Ranitidine was the most commonly prescribed H2RA in the pre-referral period (September 2017-August 2019), with incidence rates between 0.8 and 9.0/1000 person years (PY). A steep decline to 0.3-3.8/1000 PY was observed in the referral period (September 2019-March 2020), eventually dropping to 0.0-0.4/1000 PY in the post-referral period (April 2020-March 2022). Switching from ranitidine to alternative drugs increased in the post-referral period, with the majority of patients switching to PPIs. Discontinuation of ranitidine use ranged from 270 to 380/1000 users in 2017 and decreased over time.

Conclusions: Ranitidine was commonly used prior to referral, but it was subsequently discontinued and replaced primarily with PPIs.

MeSH terms

  • Cohort Studies
  • Drug Utilization
  • Female
  • Histamine H2 Antagonists* / adverse effects
  • Humans
  • Male
  • Proton Pump Inhibitors / adverse effects
  • Ranitidine* / adverse effects
  • Retrospective Studies

Substances

  • Ranitidine
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors