N-Nitrosodimethylamine-contaminated ranitidine and risk of cancer in South Korea: a nationwide cohort study

Abstract

Objective: On September 2019, the United States Food and Drug Administration announced that some ranitidine products were contaminated with unacceptable levels of N-nitrosodimethylamine (NDMA). We aimed to determine whether the use of ranitidine that was potentially contaminated with NDMA, rather than another histamine H2-receptor antagonist (H2 blocker), increased the risk of overall cancer. Methods: We performed a Korean population-based nationwide cohort study with propensity score matching of 95,656 adults (unmatched) and 55,584 adults (matched) who initiated treatment with H2 blockers between January 2005 and December 2014, and were followed until December 2015. Incident overall cancer was the primary outcome and all-cause mortality was the secondary outcome. Results: The unweighted cohort had 30,335 new users of ranitidine and 65,321 new users of other H2 blockers. The weighted cohort had 27,792 new users of ranitidine and 27,792 new users of other H2 blockers (median age, 55.0 years [interquartile range, 45-63]; 21,186 men [38.3%]). During follow-up (median of 6.8 years for ranitidine vs. 6.6 years for other H2 blockers), there were 2,840 new diagnoses of cancers and 1,758 deaths among users of other H2 blockers, and 2,113 new diagnoses of cancers and 1,933 deaths among users of ranitidine. The adjusted hazard ratio (aHR) for overall cancer in ranitidine users was 1.01 (95% confidence interval [CI], 0.95 to 1.06), with no evidence of a dose-response relationship (Ptrend=0.429) and no evidence of a duration-response relationship (Ptrend=0.549). The aHR for all-cause death in ranitidine users was 1.04 (95% CI, 0.97 to 1.11), with no significant association. The results from the unweighted cohort were similar to the primary results in the weighted cohort. Conclusions: Although our findings do not reassure keep using ranitidine, but those suggest that use of contaminated ranitidine was not markedly dangerous of cancer risk at short-term follow-up period. However, future studies are needed to investigate the long-term cancer risk and the risk of cancer in pediatric populations.