OTTAWA –Health Canada is sharing the results of its review of potential long-term health effects involving valsartan drugs that were found to contain the impurity N-nitrosodimethylamine (NDMA). Health Canada scientists have assessed the available data to determine the potential increased risk of developing cancer, to help put the risk into context for Canadians.
Based primarily on animal studies, NDMA is classified as a probable human carcinogen. This means that exposure over the long term could increase the risk of cancer. We are all exposed to low levels of NDMA. NDMA can be found in some foods (such as meats, dairy products and vegetables) and in drinking water. It is not expected to cause harm when ingested in very low levels.
Health Canada believes that NDMA was introduced to the affected valsartan drugs as a result of a change in manufacturing processes at Zhejiang Huahai Pharmaceuticals (the manufacturer of the valsartan ingredient) in 2012. The longest time affected products were on the Canadian market was approximately three years.
The amounts of NDMA present in the valsartan active ingredient varied, but on average were higher than levels that are considered reasonably safe, which is why the valsartan products were recalled. Health Canada has derived estimates of the possible increased cancer risk using internationally accepted methods and information available to the Department at this time. The estimates are based on the following assumptions:
- the valsartan active ingredient contained 60 parts per million (ppm) NDMA. This is the average reported level of NDMA in a sampling of batches.
- the exposure was approximately 3 years.
It is important to keep in mind that the actual health risk varies from person to person, and depends on factors including daily dose, how long the affected valsartan was taken, and the actual level of NDMA present in the finished product.
Estimated potential increased cancer risk for patients taking various doses of NDMA-containing valsartan products for 3 years
Valsartan dose (mg/day)
containing 60 ppm NDMA
|40||1 additional case per 93,400 people|
|80||1 additional case per 46,700 people|
|160||1 additional case for 23,300 people|
|320||1 additional case per 11,600 people|
For patients taking the highest dose of valsartan (320 mg) containing 60 ppm NDMA per tablet once daily for three years, Health Canada estimates that the potential increased risk of cancer over a lifetime could be 1 additional case of cancer for every 11,600 people taking the product. For patients taking the lowest valsartan dose (40 mg) containing 60 ppm NDMA per tablet once daily for three years, Health Canada estimates that the potential increased risk of cancer over a lifetime could be 1 additional case for every 93,400 people taking the product. To put these estimates into a broader context, nearly 1 in 2 Canadians is expected to develop cancer during their lifetime.
Health Canada is working closely with international partners to share information and coordinate efforts on inspections, risk assessments and public communications. Notably, Health Canada’s estimated potential increased cancer risk is lower than those reported by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) because the contaminated valsartan products were on the Canadian market for a shorter period of time, compared to the exposure timelines used in the assessments communicated by the FDA and EMA. Health Canada will take action should any new safety issue be identified and will continue to keep Canadians updated.
The Department continues to work with the companies to determine the root cause of the NDMA found in valsartan drugs and to verify that appropriate corrective actions are taken to prevent this situation from happening again. We are also working to determine whether other products may be impacted. This includes reviewing the manufacturing processes for potential impurities in other drugs of the same class as valsartan (referred to as angiotensin receptor blockers).
What you should do
People taking valsartan drugs should check these lists of valsartan products that have and have NOT been recalled to see if their medication is affected.
Patients taking affected valsartan medications should:
- Ask their pharmacist if they are unsure whether they are using a recalled product.
- Contact their health care provider as soon as possible to discuss treatment options if they have been using an affected product. Pharmacists may be able to provide a product not affected by the recall, or doctors may prescribe a different medication for their patients’ conditions.
- Continue taking their valsartan medication unless they have been advised to stop by their health care provider. Since the risk of cancer is with long term exposure to the NDMA impurity, there is no immediate health risk, and patients can continue to take this drug to treat their medical condition until they can discuss treatment options with their health care provider.
- Contact their health care provider if they have taken recalled valsartan products and they have concerns about their health.