Has metformin been recalled
Pro Research Analysisby 
Searched over 200M research papers
Consensus Meter
Metformin Recalls Due to Nitrosamine Impurities
Introduction to Metformin Recalls
Metformin, a widely used medication for managing type 2 diabetes, has faced scrutiny due to the detection of nitrosamine impurities, specifically N-nitrosodimethylamine (NDMA). NDMA is a potential carcinogen, and its presence in pharmaceuticals has led to several recalls to ensure patient safety.
Detection of NDMA in Metformin
International Regulatory Efforts
International regulatory bodies have been actively monitoring metformin for nitrosamine impurities. A comprehensive analysis of 1090 samples, including both active pharmaceutical ingredients (APIs) and finished dosage forms (FDFs), revealed that NDMA was detected in some batches of metformin products. Specifically, 17.8% of the FDF samples tested had NDMA levels above the acceptable intake (AI) limit of 96 ng per day, prompting recalls of these batches.
Specific Recalls
In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) recalled a batch of Rosemont Pharmaceuticals' metformin oral solution due to NDMA levels exceeding the acceptable limit. The recall was a precautionary measure, and patients were advised to continue taking their medication while seeking advice from healthcare professionals.
Regulatory Actions and Guidance
FDA Guidance
The U.S. Food and Drug Administration (FDA) has issued guidance to control nitrosamine impurities in drug products. This guidance came after the detection of unacceptable levels of NDMA in various medications, including metformin. The FDA's database indicates that over 1400 product lots have been recalled due to nitrosamine impurities, highlighting the widespread nature of this issue.
Investigating the Root Cause
Factors Contributing to NDMA Formation
Research has identified several factors contributing to the formation of NDMA during the manufacturing of metformin tablets. Key factors include the use of water and heat during intra-granulation and the nitrite/nitrate content in excipients. Studies have shown that certain excipients, such as polyvinyl pyrrolidone and hydroxypropyl cellulose, do not lead to NDMA formation even when water and heat are used. However, other excipients like hydroxypropyl methyl cellulose (HPMC) can result in NDMA levels close to the AI limit when combined with water and heat.
Conclusion
The detection of NDMA in metformin has led to several recalls to ensure patient safety. Regulatory bodies worldwide are actively monitoring and addressing this issue through stringent testing and guidance. Understanding the root causes of NDMA formation is crucial for preventing future contamination and ensuring the safety of metformin products.
Sources and full results
Most relevant research papers on this topic