.重大事件，尽量参考官方信息。

https://www.gov.uk/government/news/blood-pressure-and-heart-medication-recalled-from-pharmacies.英国MHRA。

Published 5 July 2018

From:

Medicines and Healthcare products Regulatory Agency

Pharmacies in the UK are being advised to recall all batchesof valsartan containing medicines made by Dexcel Pharma Ltd and AccordHealthcare (previously known as Actavis Group) as a precaution, the Medicinesand Healthcare products Regulatory Agency’s (MHRA) has warned today. Thisfollows an urgent investigation in to medicines containing valsartan used totreat high blood pressure and heart conditions.

Arecall is underway across Europe following recent and emerging information thatan impurity has been identified as part of the manufacturing process in avalsartan active substance manufactured at one facility based in China. Thisfacility has supplied the manufacturers with the valsartan active substance.The impurity (N-nitrosodimethylamine), which may have carcinogenic potential,is a result of a change in the manufacturing process. This active substance isused in a number of medicines marketed in Europe.

TheEuropean Medicines Agency and other EU regulators are working together toinvestigate the extent of the issue and any possible impact for patients.

Ifyou are taking any of the affected valsartan products, it is vital that you donot stop taking your medication but you should get in touch with a doctor orhealthcare professional as soon as possible. Alternative valsartan containingproducts, that are unaffected by this issue, are available in the UK.

Patientsafety is our top priority and we will provide further updates as theinvestigation progresses.

DrSam Atkinson, MHRA’s Director of the Inspection, Enforcement and StandardsDivision said:

People taking valsartan medication affected by this recallare advised to not stop taking their medication, but to speak to their doctoror healthcare professional who can advise on alternative treatment.

Wecontinue to undertake an urgent review of all these products that may pose alow risk to public health.

Wewill communicate the outcome of our investigations and ensure that any otheraffected products are recalled.

Ourhighest priority is to ensure that the medicines you take are safe.

Ifyou are concerned, please speak to your GP, pharmacist or other healthcareprofessional.

We strongly encourage anyone taking valsartan medicines toreport any suspected side effects, to us via our Yellow Card Scheme.

Notes to Editor

1.  MHRAis responsible for regulating all medicines and medical devices in the UK. Allour work is underpinned by robust and fact-based judgments to ensure that thebenefits justify any risks. MHRA is a centre of the Medicines and Healthcareproducts Regulatory Agency which also includes the NationalInstitute for Biological Standards and Control (NIBSC) and the ClinicalPractice Research Datalink (CPRD). The Agency is an executive agency of the Department ofHealth. www.mhra.gov.uk

2.  Link to Yellow Card Scheme

3.  Link to Drug Alert

 

EMA, http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2018/07/news_detail_002984.jsp&mid=WC0b01ac058004d5c1

05/07/2018

EMAreviewing medicines containing valsartan from Zhejiang Huahai followingdetection of an impurity

Somevalsartan medicines being recalled across the EU

TheEuropean Medicines Agency (EMA) is reviewing medicines containing the activesubstance valsartan that is supplied by Zhejiang Huahai Pharmaceuticals, acompany in Linhai, China.

Thereview was triggered after the company detected an impurity,N-nitrosodimethylamine (NDMA), in the valsartan activesubstance which the company supplies to manufacturers producing some ofthe valsartan medicines available in the EU.
NDMA is classified as a probable human carcinogen (a substance that could causecancer) based on results from laboratory tests. The presence of NDMA wasunexpected and is thought to be related to changes in the way the activesubstance was manufactured.

Whilethe review is underway, national authorities across the EU are recallingmedicines containing valsartan supplied by Zhejiang Huahai.

Valsartanmedicines are used to treat patients with high blood pressure in order toreduce complications such as heart attack and stroke. It is also used inpatients who have had heart failure or a recent heart attack.

EMA’sreview will investigate the levels of NDMA in these valsartan medicines, itspossible impact on patients who have been taking them and what measures can betaken to reduce or eliminate the impurity from future batches produced by thecompany. As a precaution, the review will also consider whether other valsartanmedicines may be affected.

Thereview will be carried out by EMA’s Committee for Medicinal Products forHuman Use(CHMP).

Informationfor patients

Anunexpected impurity has been found in the active ingredient used to make somevalsartan medicines.

Onlysome valsartan medicines in the EU are affected and these are being recalled.

Youshould not stop taking your valsartan medicine unless you have been told to doso by your doctor or pharmacist.

Youmay be given a different valsartan medicine (or an alternative treatment) whenyou go for your next prescription.

Ifyou have any questions about your treatment, speak to your pharmacist who cantell you if your medicine is being recalled.

Ifyou are in a clinical trial with valsartan and have any questions,speak to the doctor treating you in the trial.

EMAwill assess whether the impurity may pose any risk for patients. Furtherinformation will be provided once available.

Informationfor healthcare professionals

N-nitrosodimethylamine(NDMA) has been detected in the valsartan active substancemanufactured byZhejiang Huahai Pharmaceuticals.

As aresult, valsartan medicines containing the active substance fromZhejiang Huahai are being recalled in the EU.

Nationalauthorities are contacting pharmacists with information on the medicines to berecalled.

EMAis now evaluating potential impact on patients of the exposure to NDMA invalsartan medicines. Further information will be provided once available.

---

Moreabout the medicine

Valsartanis an angiotensin-II-receptor antagonist used to treat hypertension (high bloodpressure), recent heart attack and heart failure. It is available on its own orin combination with other active substances.

Thereview covers all medicines that contain valsartan supplied by Zhejiang HuahaiPharmaceuticals. As a precaution, the review will also consider whether othervalsartan medicines may be affected.

Moreabout the procedure

Thereview of medicines containing valsartan supplied by Zhejiang HuahaiPharmaceuticals was triggered on 5 July 2018 by the request of the EuropeanCommission, under Article 31 ofDirective 2001/83/EC.

Thereview will be carried out by the Committee for Medicinal Products forHuman Use(CHMP), responsible for questions concerning medicines for human use,which will adopt the Agency’s opinion. The CHMP opinion will then beforwarded to the European Commission, which will issue a final legally bindingdecision applicable in all EU Member States.

 

 

 

日本，http://www.pmda.go.jp/files/000224928.pdf

 

爱尔兰药监，http://www.hpra.ie/homepage/medicines/safety-notices/item?t=/recall-of-a-number-of-valsartan-containing-film-coated-tablet-products—important-information-for-patients-and-healthcare-professionals&id=fadd0a26-9782-6eee-9b55-ff00008c97d0.

 

 

Recall of a number of Valsartan-containing film coated tablet products- Important information for patients and healthcare professionals

Notice type: Recall

Date: 05/07/2018

  

Product name or type:
A number of valsartan-containing medicines. See table below. Note that not all valsartan-containingmedicines are affected by the recall. There are alternativevalsartan-containing medicines and other treatments available to patients. 

Reference:
QDR-H-18-381 

Authorisation Number:
See table below. 

Active Substance:
Valsartan  

Serial Or Batch NumberAnd Expiry Date:
See below table

Authorisation Holder:
See below table 

Prescription Required:
Yes 

Recall Classification:
Recall to pharmacy level. Advice for patients is also given. Seebelow.  

Target Audience:

·        Patients

·        Carers 

·        Pharmacists and

·        other relevant HealthcareProfessionals

Problem Or Issue:

The Health Products Regulatory Authority(HPRA) wishes to inform users and healthcare professionals of the followingquality defect for specific Valsartan products.

·        An impurity has been identifiedin the valsartan active substance used in the listed medicinal products; thisimpurity is N-nitrosodimethylamine (NDMA) and it has been classified as aprobable human carcinogen.   At present there is no evidence that thisimpurity has caused any harm to patients; however, this recall action is beingundertaken as a precautionary measure to prevent any further exposure to theimpurity in the affected medicines whilst the investigation is ongoing. 

·        The active substancemanufacturer, Zhejiang Huahai Pharmaceuticals, located in China, has reportedthat the impurity is linked to changes made to the manufacturing process.

 

This is an emerging issue. At present, therisk is theoretical and there is no direct evidence of harm having been causedby this impurity issue.  The HPRA is actively involved with the EuropeanMedicines Agency and with other medicines regulators to determine any possibleimpact on patients who have been taking these medicines.  In this regard,work is currently ongoing at a European level to better understand thepotential impact of this impurity, and as a precautionary measure at this time,this recall is being undertaken

Table 1: List of Valsartan-containing productsbeing recalled to Pharmacy Level

 

Background InformationOr Related Documents:

This active substance is used in a numberof medicines marketed in Europe and recall actions are also underway acrossEurope. 

Valsartan is an important prescriptionmedicine used to treat high blood pressure and heart failure. It is alsosometimes prescribed after a heart attack.

·        The Recall letter topharmacists 05.07.2018

·        A DearDoctor letter intended for prescribers 05.07.2018

Actions To Be Taken:

Advice to Patients

·        It is important that you do notstop taking your valsartan medicine abruptly.The health risk of abruptlydiscontinuing the medicine is higher than any potential risk presented by theimpurity.

·        This issue only applies to thevalsartan medicines listed above. If you are uncertain, your pharmacist caninform you if the medicine you are taking is affected.

·        There are other valsartanmedicines available which your pharmacist may dispense for you.If you arecurrently taking one of the above valsartan medicines, you should go back toyour pharmacy at an early opportunity and seek an alternative medicine.

·        In the event that your pharmacistis unable to dispense an alternative medicine for you, you should go to seeyour doctor at an early opportunity to discuss alternative medicines.

·        When you are going to yourpharmacy or doctor, you should bring your valsartan-containing medicine withyou.

·        If you have any concerns orquestions concerning this issue, you should consult with your doctor or otherhealthcare professional.

 

Specific Information for Pharmacists and other HealthcareProfessionals:

For All Pharmacists:

A recall letter is being issued on July 5^th,2018, to all pharmacies/pharmacists in Ireland.  This recall letter isbeing emailed at the HPRA’s request by the Pharmaceutical Society of Ireland(PSI).  Paper copies of the recall letter will also be posted out to thepharmacies by the three pharmaceutical companies whose products are beingrecalled. 

Not all valsartan-containing medicines areaffected by the recall. There are alternative valsartan-containing medicinesand other treatments available to patients.  

Please perform the following actions:

·        Immediately quarantine anyunits from the products listed above which you have in your pharmacy. Forhospital pharmacies, this includes wards, clinics and any other relevantlocations within your hospital. 

·        Please return the quarantined unitsto your wholesaler within the next 7 days.  Your wholesaler will be in aposition to advise you about receiving credit for the packs that you return

 

For Hospital Pharmacists only:

We kindly request that this communicationis highlighted and made available to the relevant consultants/healthcareprofessionalsinfo@hpra.ie withinyour hospital; for example Cardiologists, Nephrologists, strokephysicians and other hospital consultants who may prescribe theseproducts.

For Prescribers and All Healthcare Professionals:

We ask that Prescribers and otherHealthcare Professionals consider the implication of this recall on existingstocks of available alternative Valsartan supplies and, whilst theinvestigation is ongoing, it is advisable not to commence new patients onvalsartan-containing medicines where possible. 

Switching existing patients to alternativevalsartan-containing medicines which are not on the above list should befeasible at present, given current stocks. However, the situation may changeand you may have to consider other treatment options for patients requiringsuch medicines.

This an evolving situation and we willprovide further updates as new information becomes available.

Contacts:
To contact the HPRA please call 01-6764971 or email info@hpra.ie

 

香港药监，http://www.info.gov.hk/gia/general/201807/06/P2018070600841.htm?fontSize=1。

Recall of five valsartan-containing pharmaceutical products (with photos)

***********************************************************

    The Department of Health (DH) today (July 6) instructed two licensedmedicine wholesalers, namely Actavis Hong Kong Limited and Hong Kong MedicalSupplies Ltd (HK Medical), to recall five products containing valsartan fromthe market as a precautionary measure due to an impurity detected in the rawmaterial.
 
     The affected products are:
 

Product	Hong Kong  Registration Number	Registration  certificate holder
Valtensin 160mg  tablets	HK-61786	Actavis
Valtensin 80mg  tablets	HK-61787	Actavis
Valtensin HCT  tablets 160/12.5mg	HK-61784	Actavis
Valtensin HCT  tablets 80/12.5mg	HK-61785	Actavis
Valsartan Stada  80mg tablets	HK-60794	HK Medical

 
     The DH, through its surveillance system, noted that the rawmaterial valsartan produced by a manufacturer in the Mainland and used incertain pharmaceutical products as an active ingredient was found to contain animpurity, N-nitrosodimethylamine (NDMA). NDMA is classified as a probable humancarcinogen (a substance that could cause cancer) based on results fromlaboratory tests.
 
     So far, the above products registered in Hong Kong areconfirmed by the wholesalers to contain the affected raw material. The DH’sinvestigation is continuing.
 
     According to the preliminary investigation of the Mainlandmanufacturer, the presence of NDMA in the raw material valsartan is believed tobe related to its production method.
 
     Valsartan-containing products are prescription medicinesused to treat hypertension and heart failure. They are available as singleingredient products or in combination with other active ingredients.
 
     According to Actavis and HK Medical, the above productshave been supplied to local private doctors and pharmacies. The productsValtensin 80mg and 160mg tablets have also been supplied to the HospitalAuthority.
 
     Both companies have set up hotlines (Actavis: 3188 4288; HKMedical: 2806 3112) to answer related enquiries.
 
     So far, the DH has not received any adverse reactionsrelated to the above affected products.
 
     Patients who are taking the above products should not stoptaking the medicines, but should seek advice from their healthcareprofessionals for appropriate arrangement.

Photo

 

Ends/Friday, July6, 2018
Issued at HKT 20:26

CNN报道，https://edition.cnn.com/2018/07/06/health/valsartan-heart-drug-recall-intl/index.html

 

诺华中国对事件回复：

最后附上华海药业最新公告：

 公司于2018年7月7日公告了《浙江华海药业股份有限公司关于缬沙坦原料药的未知杂质中发现极微量基因毒性杂质的公告》（公告内容刊登在中国证券报、上海证券报、证券时报、证券日报及上海证券交易所网站www.sse.com.cn上）。现据公司了解的情况，欧洲药品管理局（EMA）发布了召回公告（详见：http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2018/07/news_detail_002984.jsp&mid=WC0b01ac058004d5c1）。德国、意大利、芬兰、奥地利、日本等多个国家相继发布了召回公告。以下为EMA公告的大致内容：  目前，欧洲药品管理局（EMA）正在审查含有浙江华海药业股份有限公司的缬沙坦原料药（API）的制剂。审查是由于该公司在提供给欧洲市场的部分缬沙坦制剂的原料药中意外发现一种亚硝基二甲胺（NDMA）的杂质后而展开的。  在审查期间，欧盟相关国家的政府也正在召回含有公司提供的缬沙坦原料药的制剂。  EMA将会调查缬沙坦制剂中NDMA含量和对服用该药的患者的潜在影响，以及减少或消除未来公司供应的缬沙坦原料药中该杂质的方法和措施。除此之外，作为预防性措施，该审查还将调查其它缬沙坦药物是否亦可能受到影响。  同时，EMA报告还指出，目前正在评估缬沙坦药物内NDMA对患者的潜在影响,该杂质是否可能对患者造成任何风险，EMA将在第一时间告知。  截止本公告日，尚未了解到美国食品药品监督管理局（FDA）对该事项的处理情况。  目前公司需要根据客户对其制剂召回的情形、制剂及原料药的库存量等作出 有效的判断，进而根据与客户签订的供应协议、质量协议和其他相关交易文件，与客户协商解决方案后，才能评估因客户对其产品召回将会给公司带来的影响。公司正积极与客户进行协商，以将影响降到最低。

始发于微信公众号： 药物简讯