DSEN Abstract
Prescription patterns of ranitidine, nizatidine, famotidine, and cimetidine in Canada

A study conducted by the Canadian Network for Observational Drug Effect Studies (CNODES)

Summary and Key Messages

This large drug utilization review of histamine-2 receptor antagonists (H2RA) involved over ten million Canadians in six provinces.
Ranitidine was the most commonly dispensed H2RA.
Between 1996 and 2019, ranitidine use declined substantially in persons aged > 65 y and remained stable in those < 65 y.
Even in the most recent period (2015 - 2019), there was still substantial exposure to ranitidine in the population: an estimated mean of 130 million Defined Daily Doses annually in five provinces.
The population exposure to ranitidine can also inform a pharmacoepidemiologic study of cancer risk in Canada. CNODES is well positioned to undertake a large study of the risk of ranitidine exposure and cancer.

Project Lead & Team

This research was funded by CIHR – Drug Safety and Effectiveness Network and conducted by CNODES.

For more information, please contact info@cnodes.ca.

What is the issue?

Histamine-2 receptor antagonists (H2RA: ranitidine, nizatidine, famotidine and cimetidine) are commonly used to treat heartburn.
In September 2019, Health Canada stopped the distribution of ranitidine due to potentially high concentrations of the possible carcinogen N-nitrosodimethylamine (NDMA).

What was the aim of the study?

This study, conducted by CNODES, examined the patterns of dispensed H2RAs in Canada by describing demographic and clinical characteristics of users and prescribers and by quantifying rates of use and population exposures.

How was the study conducted?

CNODES conducted a population-based serial cross-sectional design using prescription claims from community pharmacies in Nova Scotia, Ontario, Manitoba, Saskatchewan, Alberta, and British Columbia).
Demographic and clinical characteristics of users and prescribers were characterized among subjects newly dispensed an H2RA from 2015 to 2019.
Rates of use and population exposures from 1996 to 2019 were calculated using mean annual dispensation rates and standardized/cumulative Defined Daily Doses.
Results presented by age ≥ 65 years (5 provinces) and < 65 years (MB, SK, BC).

What did the study find?

Overall number of people dispensed at least one H2RA:
- ≥ 65 years: over 4.6 million; < 65 years: over 22 million
Ranitidine prescriptions dispensed:
- ≥ 65 years: over 2.4 million; < 65 years: 1.7 million
Other H2RA prescriptions dispensed:
- ≥ 65 years: 0.7 million; < 65 years: 0.6 million
Analysis of contemporary H2RA users (2015 - 2019)
- Ranitidine accounted for > 90% of H2RAs dispensed (60% - 65% dispensed to women)
- H2RAs were most commonly prescribed by primary care physicians
- Most switches from H2RAs were to a proton pump inhibitor
Analysis of rates of dispensations (1996 - 2019)
- For both age groups (≥ 65 years and < 65 years), ranitidine was the most commonly used H2RA and the temporal changes in use followed the same patterns for both sexes
- ≥ 65 years: ranitidine use peaked 1996 - 2004 and subsequently declined
- < 65 years: ranitidine use remained stable 1996 - 2019
Analysis of population exposures to ranitidine (1996-2019)
- ≥ 65 years: highest standardized DDDs in NS
- < 65 years: highest standardized DDDs in SK
- Estimated annual mean of 130 million ranitidine DDDs.

Link to publication: Levy et al, 2023.