Recall of valsartan blood pressure medicine

Impurities that could potentially be harmful to health have been found in variants of medicines containing the active substance valsartan. The medicine is used to treat hypertension and heart failure. Patients treated with these medicines are therefore advised to contact their doctor as soon as possible in order to be switched to another type of medicine.

All sale of the affected medicines has been stopped from the Danish pharmacies.

The Danish Medicines Agency recommends that patients treated with the affected valsartan-containing medicines should be switched to another treatment alternative as soon as possible. It is emphasised that the Danish Medicines Agency assesses that it is associated with an insignificant risk for patients to continue treatment for a short period of time until they have had an opportunity to contact their doctor.

About 1,500 people in Denmark are currently being treated with valsartan-containing medicine.

Advice to patients

• If you are treated with one of the affected products on the above list, you should contact your doctor as soon as possible so that you can be switched to another medicine. You should not stop treatment without first having talked to a doctor because the medicine is still working on your disease.
• Only some valsartan-containing medicines are being recalled, not all valsartan-containing medicines. If your medicine is not on the above list, your medicine is not recalled, and you should continue your treatment as normal. 

The incident involves impurities that have been found in the affected medicines. These impurities may potentially cause cancer if they are used for a long time. At the present time, it appears that the impurities identified may have been present in the medicines in the past five years. Patients who have received treatment for a long time, may therefore have been exposed to these impurities for several years.

The Danish Medicines Agency is working closely with other European medicines agencies and we will provide current updates about the issue on dkma.dk.

Information for doctors

The impurity found in the affected products is N-Nitrosodimethylamine (NDMA), which is classified as a probable human carcinogen.

Valsartan is an angiotensin II receptor antagonist used to treat hypertension and heart failure. It is available as a single-substance product or in combination with other active substances.

Patients who are treated with valsartan products appearing on the above list can be switched to other valsartan products or another angiotensin II receptor antagonist (candesartan, irbesartan, losartan, olmesartan and telmisartan).

Patients who are treated with combination products with valsartan and hydrochlorothiazide appearing on the above list can switch to treatment with other valsartan-hydrochlorothiazide combination products, to treatment with the mono components, i.e. a valsartan tablet (not on the list) as well as a hydrochlorothiazide tablet or a combination product of hydrochlorothiazide + candesartan/irbesartan/losartan/olmesartan/telmisartan.

The Danish Medicines Agency has written a question and answers document (Q&A - in Danish only) that can aid and support doctors in their interaction and guidance of their patients. The Q&A will be updated continually.

Follow-up

On 5 July 2018, the European Commission triggered a review of valsartan medicines in relation to an impurity found in the valsartan active substance manufactured by Zhejiang Huahei Pharmaceuticals. The review is being carried out by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP).

The review covers all medicines that contain valsartan supplied by Zhejiang Huahai Pharmaceuticals and as a precaution, the review will also consider whether other valsartan medicines may be affected. The review is to investigate the impact that use of medicines containing the NDMA impurity may have on patients, and seek to establish knowledge about how long and at what levels patients might have been exposed to NDMA. The review is expected to be finalised on 20 September 2018. For more information about the review visit EMA’s website.

The Danish Medicines Agency is in dialogue with the Danish Health Authority, the Danish Patient Safety Authority, the Danish Society of Cardiology, the Danish College of General Practitioners, etc. with a view to following up on patients who have been exposed to the impurity. In addition, we are presently analysing the supply condition for the medicines that are to be used as alternatives for the affected valsartan products.

The impurities have so far only been observed in valsartan products where some of the active substances have been manufactured at the Chinese company Zhejiang Huahai Pharmaceuticals, Chuannan Site, Duqiao, Linhai, China. The NDMA impurity was unexpected, and was not detected by routine tests carried out by Zhejiang Huahei. The active substances from the Chinese company have been sold to several pharmaceutical manufacturing facilities around the world. The words Made in China will therefore not appear on all of the packages being recalled. It is the manufacturer of the finished medicinal product that must be written on the package, and it could very well be another country than the one where the active substance was manufactured.

Check the list of valsartan-containing products to see if your medicine has been recalled.

Update 10 August

The impurity has also been detected in the valsartan active substance manufactured by three other companies in China and India. This does not affect products on the Danish market.