More than five years after ranitidine products were withdrawn due to concerns about nitrosamine contamination, a reformulated version of the medication has been approved for re-entry into the U.S. market. The decision follows extensive testing and manufacturing changes aimed at preventing the formation of N-Nitrosodimethylamine (NDMA), a probable human carcinogen.
Why Ranitidine Was Removed
In 2020, regulators requested the removal of all prescription and OTC ranitidine—widely known by the brand name Zantac—after studies showed that NDMA levels could increase when the drug was exposed to elevated temperatures during storage. Ranitidine, an H2 receptor antagonist, had previously been used for GERD, peptic ulcers, and other acid-related conditions.
What Has Changed
The newly approved formulation underwent additional safety assessments and process improvements designed to minimize NDMA formation. According to the agency’s announcement, the updated version maintains the therapeutic effectiveness of prior formulations while incorporating enhanced controls.
Updated product labeling will include new storage and handling instructions, including recommendations to protect tablets from moisture, keep bottles sealed, and discard unused tablets after three months once a package has been opened.
Healthcare providers are encouraged to work with patients currently using alternative acid-reducing therapies to determine whether switching back to ranitidine is appropriate.
Part of a Broader Effort on Nitrosamine Impurities
The reintroduction of ranitidine aligns with ongoing regulatory initiatives addressing nitrosamine risks across the pharmaceutical sector. Research into nitrosamine drug substance–related impurities (NDSRIs) remains a priority area, with efforts focused on understanding how drug components contribute to impurity formation and developing standardized approaches for ANDA applicants to assess risk.
Manufacturers have also been asked to complete updated NDSRI evaluations for approved products and implement measures to mitigate potential contamination.
Looking Ahead
The return of reformulated ranitidine represents a significant milestone in balancing patient access with evolving safety expectations. As oversight of nitrosamine risks continues to advance, manufacturers will need to ensure ongoing compliance with updated testing, formulation strategies, and risk assessment practices.
At EMMA International, we support drug developers and manufacturers as they navigate shifting quality and regulatory requirements—from impurity assessments to labeling updates and compliance planning. Our team is prepared to help organizations adapt to emerging standards and maintain patient safety at every step of the product lifecycle.
For more information on how EMMA International can assist, visit www.emmainternational.com or contact us at (248) 987-4497 or info@emmainternational.com.
Reference:
Eglovitch, J. S. (2025, November 26). FDA allows reformulated ranitidine back on the market. Regulatory Focus. Regulatory Affairs Professionals Society.
U.S. Food and Drug Administration. (2025). FDA announces approval of reformulated ranitidine and updated nitrosamine risk mitigation practices. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2025). Nitrosamine impurities: Guidance and research priorities for FY2026. Center for Drug Evaluation and Research.
