Trace amounts of a nitrosamine impurity found in individual diabetes medicines

Isolated traces of the nitrosamine NDMA have been detected in individual diabetes preparations with the active substance metformin – investigations are ongoing worldwide.

06.12.2019

The Swissmedic laboratory (OMCL) has detected levels of contamination with NDMA that exceed the internationally tolerated safety limit for medicinal products in certain metformin preparations. The laboratory tests will continue until Swissmedic is certain that all Swiss metformin products are of flawless quality.

Because nitrosamines are considered to be potentially carcinogenic, there is no place for them in medicinal products. In 2018, unacceptable quantities of the nitrosamine NDMA (N-nitrosodimethylamine) were discovered in certain blood pressure-lowering medicines, and the affected batches were taken off the market. Since then, regulatory authorities across the globe have jointly been investigating possible causes.

Depending on the manufacturing process involved, contamination with nitrosamines can occur not only in sartans, but also in other active pharmaceutical ingredients (API) and drug products – in autumn 2019, all preparations containing the active substance ranitidine had to be taken off the market because they contained traces of NDMA.

Like the national regulatory authority HSA in Singapore, the Swissmedic laboratory (OMCL) has detected levels of contamination with NDMA that exceed the internationally tolerated safety limit for medicinal products in certain metformin preparations.

The active substance metformin is used in the treatment of type 2 diabetes to lower blood sugar levels and improve sugar metabolism by the body. Because diabetes preparations containing this active ingredient are widely used for treating type 2 diabetes, the extent and causes of the discovered cases of contamination will be carefully investigated in order to identify affected batches and take them off the market.

 

Important: Patients taking metformin medicines must not stop taking them on their own initiative. A sudden rise in the blood sugar level involves far greater health risks than possible traces of NDMA in the medicines concerned. The quantities of nitrosamine found are very low and do not pose any short-term health risk.

 

Nitrosamines occur in food products, cosmetics and everyday objects and can even be formed in the body itself. The discovered traces of NDMA are roughly equivalent to the quantities that can enter the body via food, the skin or the airways. But the precautionary principle applies, i.e. that the intake of these substances, which can cause cancer at high concentrations, should be avoided wherever possible.

Since the withdrawal of sartan-containing medicines from the market in summer and autumn 2018 due to nitrosamine contamination, the Swissmedic laboratory has extended its investigations to include other substances. In order to be able to detect cases of nitrosamine contamination with even greater sensitivity, the Swissmedic OMCL has been developing and publishing its own test methods.

Moreover, Swissmedic has asked all marketing authorisation holders of human medicinal products to evaluate possible risks of any contamination of their preparations with nitrosamines and take precautionary measures to keep these products free of nitrosamines as far as possible.

Metformin is used for the treatment of type 2 diabetes. Its active ingredient lowers blood sugar levels by reducing the body's own sugar production and restricting the absorption of sugar from the bowel into the blood stream.

Under no circumstances should patients taking the metformin preparations stop taking their medication on their own initiative. Those individuals affected should ask their doctor/pharmacist for advice.

See also

29.11.2019

Laboratories (OMCL)

Swissmedic laboratory publishes another extended test method for nitrosamines in sartans

23.09.2019

Recall of all preparations containing ranitidine from the Swiss market

Gastric acid blocker contaminated with traces of NDMA – use available alternative treatments for this indication.