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

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.

Fig. 1

Incidence rate trends of ranitidine use by calendar year. Vertical dashed lines indicate referral initiation and finalisation. DA Disease Analyser, IMRD IQVIA Medical Research Data, IPCI Integrated Primary Care Information, LPD Longitudinal Patient Database, py person years, SIDIAP Information System for Research in Primary Care

Fig. 2

Incidence rate patterns of other H₂RA use by referral period. DA Disease Analyser, H₂RA histamine H₂-receptor antagonist, IMRD IQVIA Medical Research Data, IPCI Integrated Primary Care Information, LPD Longitudinal Patient Database, py person years, SIDIAP Information System for Research in Primary Care

Fig. 3

Incidence rate patterns of PPI use by referral period. DA Disease Analyser, IMRD IQVIA Medical Research Data, IPCI Integrated Primary Care Information, LPD Longitudinal Patient Database, PPI proton-pump inhibitor, py person years, SIDIAP Information System for Research in Primary Care

Fig. 4

Incidence rate patterns of early switching (within 90 days) from ranitidine use to alternative medicine use. Vertical dashed lines indicate referral initiation and finalisation. DA Disease Analyser, GERD gastro-oesophageal reflux disease, H₂-receptor antagonists (excluding Ranitidine), IMRD IQVIA Medical Research Data, IPCI Integrated Primary Care Information, LPD Longitudinal Patient Database, PPI proton-pump inhibitor, SIDIAP Information System for Research in Primary Care

Fig. 5

Incidence rate patterns of discontinuation of ranitidine use (gap of more than 90 days). Vertical dashed lines indicate referral initiation and finalisation. DA Disease Analyser, IMRD IQVIA Medical Research Data, IPCI Integrated Primary Care Information, LPD Longitudinal Patient Database, SIDIAP Information System for Research in Primary Care

Fig. 6

Incidence rate patterns of ranitidine prescription in individuals newly diagnosed with conditions for which ranitidine or alternative drugs are indicated. Vertical dashed lines indicate referral initiation and finalisation. DA Disease Analyser, IMRD IQVIA Medical Research Data, IPCI Integrated Primary Care Information, LPD Longitudinal Patient Database, SIDIAP Information System for Research in Primary Care