Higher cumulative exposure to ranitidine does not increase cancer risk, shows large scale study

On evaluating the risk of overall cancer and nine cancers by specific sites in people treated with ranitidine with NDMA impurities versus those treated with other H2RAs, a Korean researcher's team found that higher cumulative exposure to ranitidine did not raise the cancer risk. The study's results appeared in the journal Scientific Reports.

"We found no association between ranitidine with potential NDMA impurities and risk of major individual malignancies and overall cancer," Ju-Young Shin, Sungkyunkwan University, Seoul, Republic of Korea, and colleagues stated.

NDMA is a volatile chemical that belongs to the nitrosamine class of compounds. It is a by-product of manufacturing processes comprising alkylamines that leaches into the water, air, and soil. Human exposure to NDMA can occur through food items, tobacco smoke, and nitrite-preserved foods, such as household goods and cured meats. Also, it can be formed in the stomach endogenously during the digestion of foods containing alkylamines.

NDMA is known to be carcinogenic in animals, but in humans, the data is scarce. Based on laboratory studies, NDMA has been classified by the IARC (International Agency for Research on Cancer) as possibly carcinogenic to humans (group 2A).

In recent years, the most critical issue related to NDMA seems to be pharmaceutical contamination. In pharmaceutical products containing valsartan, an antihypertensive drug, NDMA was detected above the acceptable level in 2018. Subsequently, its detection was made in nizatidine, metformin, and ranitidine products. In particular, NDMA impurities in ranitidine have raised significant concern as ranitidine is widely used both as a prescription and an over-the-counter drug. Some evidence suggests that NDMA can arise from ranitidine's degradation itself with increasing levels over its shelf life. Also, ranitidine is suspected of NDMA production in the human body.

Considering the above, the need arises for a study where the use of ranitidine itself is linked to cancer risk, irrespective of whether NDMA was detected in individual ranitidine products.

To examine the cancer risk among ranitidine-treated people, a cohort study was conducted using the National Health Insurance Service-National Sample Cohort data (2002–2015) of South Korea. Patients aged 40 and above began receiving ranitidine or other H2RA's, active comparator without a history of H2RA prescription during the prior two years. The lag time was designated as up to 6 years. The outcomes included the overall incidence of cancer risk and the risk of major single cancers during the follow-up. The association between ranitidine use and cancer risk was examined. Following propensity score matching and exclusion, 25,360 patients were included.

The team found that ranitidine use was not linked with overall cancer risk and major individual malignancies; [overall cancer: incidence rate per 1000 person-years, 2.9 vs 3.0 among the ranitidine users and other H2RAs users, respectively; adjusted hazard ratio (HR) for all cancers, 0.98].

To conclude, the study provided no evidence of the association of NDMA impurities in ranitidine products with cancer risk. Due to lack of power, not much can be suggested about individual cancers.

"The follow-up period of the study was 5.5 years, not long enough to assess long-term cancer risk," the authors on the side wrote. "The findings should be considered as a short-term cancer risk," the authors additionally warranted about their study 

Reference:

Joung, KI., Hwang, J.E., Oh, IS. et al. association between ranitidine use with potential NDMA impurities and risk of cancer in Korea. Sci Rep 12, 22396 (2022). https://doi.org/10.1038/s41598-022-26691-0