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Health Sciences Authority

HSA Recalls Three Brands of Losartan Medicines from Hetero Labs Ltd

The Health Sciences Authority (HSA) is recalling three brands of blood pressure medicines, which contain a losartan ingredient that was manufactured by Hetero Labs Limited. These products were found to contain trace amounts of a nitrosamine impurity, N-nitroso-N-methyl-4-aminobutyric acid (NMBA), which are above internationally acceptable levels.

2    Patients are advised not to stop treatment on their own as there is no immediate health risk associated with taking the affected medicines. We have advised healthcare professionals to review the medicine and treatment plans of their patients.

3    Not all losartan medicines are affected by this recall. Only three out of the ten losartan products in Singapore contain unacceptable levels of nitrosamine impurity.

Table A: List of recalled losartan medicines

Product name

Active ingredient

Strength

Local supplier

Hyperten Tablet

Losartan Potassium

50mg

Goldplus Universal Pte Ltd

100mg

Losagen Tablet

Losartan Potassium

50mg

Medicell Pharmaceutical (S) Pte Ltd

100mg

Losartas Tablet

Losartan Potassium

50mg

Apotheca Marketing Pte Ltd

100mg

Please refer to Annex A of the pdf version for pictures of the medicines and their packaging.

4    Losartan belongs to a class of medicines called angiotensin II receptor blockers (ARBs), which are used to treat high blood pressure, also known as hypertension. In addition to the three recalled brands, there are seven other brands of losartan medicines marketed in Singapore. These seven brands have been tested by HSA and do not contain NMBA. Please refer to Annex B of the pdf version for the seven brands.

Background

5    Since June 2018, several ARB medicines have been recalled overseas due to the presence of two other nitrosamine impurities[1], N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA). HSA had tested the locally marketed ARB medicines and none of them were found to contain unacceptable levels of the two impurities. The list of ARB medicines recalled overseas and HSA’s corresponding actions are below:

a) In end-June 2018, several valsartan-containing medicines were recalled overseas due to the presence of NDMA. Based on HSA’s checks, none of valsartan products marketed in Singapore were affected.

b) In September 2018, several overseas regulatory agencies recalled affected ARBs due to the presence of NDEA. HSA had tested the ARBs marketed in Singapore and none were found to contain unacceptable levels of these impurities. Since November 2018, HSA has required companies to test for these impurities in their products and comply with international standards, to ensure the continued quality of the products imported into Singapore.  

6    Since end-February 2019, several losartan medicines were recalled overseas due to the presence of NMBA. HSA has tested all locally marketed losartan products for the presence of the new NMBA impurity. By testing all brands of losartan medicines available locally beyond Hetero Labs products, HSA is able to advise which brands did not contain NMBA, and help healthcare professionals decide on suitable alternatives for patients in place of the recalled brands.

7    Tests and reviews were completed on 21 March 2019 and three brands – Losartas, Losagen and Hyperten ‒ were found to contain trace amounts of NMBA that are above acceptable levels. The other seven brands of losartan products were not affected by this impurity. HSA has completed testing all other ARB medicines marketed in Singapore, and no other ARB medicines except these three are affected by this impurity.

8    HSA is working with companies and international regulatory agencies to verify the cause of contamination, and to formulate measures to address the issue. HSA will require companies to make the necessary changes to their manufacturing process to ensure that the medicines do not contain these impurities in future.

Consumer advisory

9    The risks of trace amounts of NMBA are associated with long term exposure[2].  Sudden stopping of the medicines can pose greater and more immediate risk to patient’s health.

10    Professor Ding Zee Pin, Cardiologist in the National Heart Centre Singapore and HSA’s Expert Panel on Nitrosamines advises: “There is no immediate health risk associated with taking the affected medicines, and patients are advised not to stop or change treatment on their own. As losartan is used to treat high blood pressure, stopping the medicine without replacement of other equivalent medication can increase the risk of poor control of blood pressure.”  

11    HSA advises consumers who are taking the three affected brands of losartan medicines on the following:

a) Do not stop taking the medicines on your own until you have been provided with a replacement brand of losartan or a different medicine by your healthcare provider.

b) Discuss your medication and treatment plan with your healthcare provider.  Your healthcare provider has been advised to make arrangements to review and provide you with alternatives or other therapies.

c) Only three of the ten losartan products in Singapore – Hyperten, Losagen and Losartas – contain the nitrosamine impurity. Consult your healthcare provider if you are unsure if you are taking an affected brand. 

12    Consumers can contact the HSA hotline at Tel: 6866 3538 or email: contact_hprg@hsa.gov.sg if you have further enquiries.

13    More details and updates on this issue of nitrosamine contamination of ARB medicines are posted on the HSA website at this link: https:// www.hsa.gov.sg/sartanupdates

HEALTH SCIENCES AUTHORITY
SINGAPORE
28 MARCH 2019

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[1] Nitrosamines are environmental contaminants and they are also found in food or the environment in very minute amounts. Studies have reported that exposure over a prolonged period to doses of nitrosamine impurities (including NDMA, NDEA and NMBA) that are much higher than usual human exposure could cause cancer in animals. Exposure to nitrosamines at high quantities over a long-term period may potentially increase the risk of cancer.

[2] For example, the added cancer risk from an additional 6-month exposure is estimated to be less than 0.0002%.