THE METFORMIN-CONTAINING MEDICINES THAT ARE REGISTERED AND IN PROCESS

The South African Health Products Regulatory Authority (SAHPRA), in collaboration with other regulatory agencies, are reviewing the final pharmaceutical products for immediate and extended release dosage forms containing metformin hydrochloride as an active substance. This review was triggered because of the detection of an impurity, N-nitrosodimethylamine (NDMA) in the metformin hydrochloride which were observed to be above the acceptable intake limit.

SAHPRA previously issued a press release regarding the notice of concern regarding metformin (17 January 2020).

NDMA is classified as a probable human carcinogen (a substance capable of causing cancer) based on the results from laboratory tests. The presence of these impurities appears to be generated by the reaction of a secondary amine (which may be present as an impurity or degradant in the solvents and reagents used) and sodium nitrite under acidic conditions where nitrous acid is formed. Although the exact source of the impurity is yet to be determined, it is possible that NDMA may form from the degradation of metformin, even after normal storage conditions.

SAHPRA is currently reviewing the levels of NDMA and any other N-nitrosamine impurities in these metformin containing medicines and the measures that can be taken to reduce or eliminate the impurity from future batches produced by companies.

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