News Category: Regulatory news
Updated on 28/11/2018
The HPRA is today proceeding with the precautionary recall of certain parallel imported Valsartan products. This is a targeted recall. Only those pharmacies that received stock of the products in question are directly impacted by this recall action.
Further information, including list of importer companies,copies of the recall letters and a full list of all valsartan-containing medicines impacted by this recall to-date, are available from the Valsartan section of our website.
Previous updates
Review of impurities extended to other sartan medicines
The European review of the impurities in valsartan has been extended to other sartan-containing medicines, following the detection of very low levels of the impurity N-nitrosodiethylamine (NDEA) in another sartan active substance, losartan, manufactured by the company Hetero Labs in India. Further tests are required to determine the extent of the impurity in the product and whether it is present above levels that can be considered acceptable.
Based on the trace amounts of NDEA seen so far, there is no immediate risk to patients. Patients are therefore advised not to stop taking losartan or other sartan medicines without speaking to their doctor or pharmacist.
The HPRA continues to be actively involved in this issue and is working with the European Medicines Agency (EMA) and other European regulators. Additional details are available on the EMA website and further updates will be provided as new information becomes available.
Update 02/08/2018
The EMA is conducting a review of the possible health effects in patients who may have taken valsartan medicines containing NDMA – an impurity found in the active substance manufactured by Zhejiang Huahai Pharmaceuticals.
NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on animal tests. It is present in some foods and water supplies but is not expected to cause harm when ingested in very low levels.
The EMA has now published a preliminary assessment of the possible cancer risk associated with valsartan medicines containing NDMA. This preliminary assessment, which has been extrapolated from animal studies, estimates that there could be one extra case of cancer for every 5,000 patients taking the affected medicines at the highest valsartan dose (320 mg) every day for 7 years.
The EMA notes that this estimate should be considered in the context of the lifetime risk of cancer in the EU (1 in 3) and NDMA exposure from other sources. It is also based on the assumption that the NDMA present in the active substance is carried over in the final product in the same amount. Further details are available from the EMA website.
According to the EMA, this issue presents no immediate risk to patients. Patients taking the affected medicines who have not yet switched to an alternative should not stop taking their medicines without consulting their doctor or pharmacist.
The HPRA will publish details of the final review findings once available.
Update 18/07/2018
The EMA has confirmed that its review of valsartan medicines in relation to the impurity NDMA is now underway. NDMA was recently identified as part of the manufacturing process in the valsartan active substance produced by Zhejiang Huahai Pharmaceuticals. Over the past two weeks, national medicines authorities, including the HPRA, have been recalling medicines containing valsartan from this manufacturing facility.
The EMA will consult toxicology experts to better understand the impact that use of medicines containing NDMA may have on patients and it is making this aspect of the review a priority. While further assessment is needed, there is no immediate risk and patients taking valsartan are advised not to stop their treatments unless they have been advised to do so by their pharmacist or doctor. The EMA will provide further updates in respect of its review as soon as new information becomes available.
Further details are available on the EMA website.
Update 11/07/2018
The HPRA is today proceeding with the precautionary recall of certain parallel imported Valsartan products. This is a targeted recall. Only those pharmacies that received stock of the products in question from the parallel importer companies – Eurodrug/Imbat, IMED Healthcare and PCO – are directly impacted by this recall action. As a result, the volume of packs that will be recalled on this occasion is significantly lower than in the earlier recall of 5 July 2018.
Further information, including copies of the recall letters and a full list of all valsartan-containing medicines impacted by this recall to-date, are available from the Valsartan section of our website.
The vast majority of patients taking valsartan-containing medicines will not be impacted by this extended recall and patients are not being asked to take any action at this point. Those patients who may have been in receipt of the products in question will be contacted directly by their pharmacist who will advise them on any actions required.
Update 07/07/2018
Additional stocks of unaffected valsartan-containing medicines became available for wholesalers yesterday, Friday July 6th. Further supplies to that mentioned yesterday will also be available on Monday morning July 9th for ordering by pharmacies. While the stock situation will remain constrained there should be adequate supplies next week to meet immediate patient needs.
Update 06/07/2018
The HPRA wishes to advise that the supply of unaffected valsartan-containing medicines is becoming constrained at this time and that it is working with manufacturers and wholesalers in relation to the issue. New stocks of unaffected valsartan-containing medicines are expected to be available in Ireland next week, but the supply situation is likely to remain constrained for a period of time.
The Medicines Management Programme have issued guidance on their webpage for prescribers who may need to consider alternative medicines to valsartan if supplies of valsartan are not available. Please see Angiotensin II receptor blockers (ARBs) - Guidance for Prescribers.
This is an evolving situation and it is recommended to monitor the HPRA website in the coming days for any updates. We also recommend registering on the HPRA website for any alerts.
Media Statement - 05/07/2018
The HPRA today states it is undertaking a precautionary recall of a number of specific medicines* containing the active ingredient valsartan that are used to treat blood pressure and heart conditions. A recall is underway across Europe following recent and emerging information that an impurity has been identified as part of the manufacturing process in a valsartan active substance manufactured at one facility in China. This active substance is used in a number of medicines marketed in Europe. Valsartan is an important prescription medicine used to treat high blood pressure and heart failure. It is also sometimes prescribed after a heart attack. The HPRA advises patients not to stop taking these important medicines but to go to their pharmacist or doctor at an early opportunity to discuss their treatment. Not all valsartan medicines are affected by the recall. There are alternative valsartan-containing medicines and other treatments available to patients. A list of the affected products is available on www.hpra.ie/valsartan
The impurity N-nitrosodimethylamine (NDMA) that has been found is classified as a probable carcinogen. At present there is no evidence that this impurity has caused any harm to patients; however, this recall action is being undertaken as a precautionary measure to prevent any further exposure to the impurity in the affected medicines whilst the investigation is ongoing.
According to Dr Lorraine Nolan, Chief Executive, HPRA, this is an emerging situation being managed in real time by the HPRA working with the European network of medicine regulators in order to determine the extent of the issue. “Laboratory testing and risk assessments will provide more information as part of this co-ordinated European approach to establish the possible impact on patients who have been taking these medicines and to ascertain if other products may be impacted. At this time, a precautionary recall of implicated products is the most appropriate action to protect patient health. We are engaging with healthcare professionals to manage this situation.”
Advice to Patients:
- Patients should not stop taking their treatment abruptly. The health risk of abruptly discontinuing this medicine is higher than any potential risk presented by the impurity.
- Patients who are taking valsartan-containing medicines should, if possible, access the HPRA website at www.hpra.ie where a list of the affected medicines is given.
- Patients should contact their pharmacist at an early opportunity for further advice.
In addition to working closely with the European regulatory network on the investigation, the HPRA is informing all stakeholders including the Department of Health, the Pharmaceutical Society of Ireland (PSI), the Irish College of General Practitioners (ICGP) and other healthcare professionals of this ongoing regulatory action.
The HPRA will provide further updates on this matter as more information becomes available.
ENDS
FOR MEDIA QUERIES:
Siobhan Molloy/ Jo Twamley (01) 679 86 00
Weber Shandwick PR 086 817 5066 / 085 1438320
FOR ALL OTHER QUERIES:
Please contact the HPRA at 01-6764971 or info@hpra.ie
* List of Valsartan-containing products being recalled to Pharmacy Level
| Product Name | PA Number | Marketing Authorisation Holder Name | Batch Numbers |
| Valtan 40 mg film-coated tablets | PA0126/211/001 | Clonmel Healthcare Ltd. | 72733 |
| Valtan 80 mg film-coated tablets | PA0126/211/002 | Clonmel Healthcare Ltd. | 73920 72293 70489 |
| Valtan 160 mg film-coated tablets | PA0126/211/003 | Clonmel Healthcare Ltd. | 73338 72325V 64314 |
| Co-Vatan 80 mg/12.5 mg Film-coated Tablets | PA0711/182/001 | Rowex Ltd. | All In-date Batches |
| Co-Vatan 160 mg/12.5 mg Film-coated Tablets | PA0711/182/002 | Rowex Ltd. | All In-date Batches |
| Co-Vatan 160 mg/25 mg Film-coated Tablets | PA0711/182/003 | Rowex Ltd. | All In-date Batches |
| Vatan 40 mg Film-coated Tablets | PA0711/183/001 | Rowex Ltd. | All In-date Batches |
| Vatan 80 mg Film-coated Tablets | PA0711/183/002 | Rowex Ltd. | All In-date Batches |
| Vatan 160 mg Film-coated Tablets | PA0711/183/003 | Rowex Ltd. | All In-date Batches |
| Valsartan Actavis 40 mg film-coated tablets | PA1380/022/001 | Actavis Group PTC | All In-date Batches |
| Valsartan Actavis 80 mg film-coated tablets | PA1380/022/002 | Actavis Group PTC | All In-date Batches |
| Valsartan Actavis 160 mg film-coated tablets | PA1380/022/003 | Actavis Group PTC | All In-date Batches |
| Valsartan/Hydrochlorothiazide 80 mg/ 12.5 mg Film-coated Tablets | PA1380/101/001 | Actavis Group PTC | All In-date Batches |
| Valsartan/Hydrochlorothiazide 160 mg/ 12.5 mg Film-coated Tablets | PA1380/101/002 | Actavis Group PTC | All In-date Batches |
| Valsartan/Hydrochlorothiazide 160 mg/ 25 mg Film-coated Tablets | PA1380/101/003 | Actavis Group PTC | All In-date Batches |