Valisure Finds Another Carcinogen in Blood Pressure Medicine Valsartan, dimethylformamide (DMF)

The most used blood pressure medicine Valsartan, seem to attract troubles like a magnet does iron particles. The newest trouble is a solvent called dimethylformamide or commonly known as DMF, is classified by the World Health Organization as a probable carcinogen. The FDA allows drugs to contain the equivalent of about 8.8 million nanograms of daily exposure to DMF. The agency last revised its allowable solvent levels in 2017; the WHO classified DMF as a probable carcinogen in 2018.

A solvent called dimethylformamide was discovered in the drug valsartan made by several companies, including Swiss pharmaceutical giant Novartis AG, and some companies that were deemed safe by FDA after the recent recalls of valsartan, according to a filing last week to the Food and Drug Administration by New Haven, Connecticut-based Valisure.
Valisure runs an FDA registered facility and its results were verified by Emery Pharma, an FDA-registered research lab in Alameda, California.

“Medicines are kind of like used cars: By the time you get it it’s already five or six years old, it’s touched hundreds of hands and it’s got 100,000 miles on it,” Valisure Chief Executive Officer David Light said in an interview.

Once facts were revealed, none denied the possibility of contamination. Some drugmakers whose pills tested positive for DMF said that neither they nor the outside companies that produce active ingredients for their drugs use the solvent, though some indicated they don’t have complete visibility into their supply chain. Some of the valsartan that was positive for DMF was on a list of medicines the FDA had earlier deemed safe to use amid the recalls, including drugs manufactured by Alembic Pharmaceuticals Ltd. and Macleods Pharmaceuticals Ltd., both based in India.

Alembic doesn’t use DMF in its manufacturing process, according to spokesman Ajay Desai, who said the contamination likely occurred during analysis. A representative for Macleods couldn’t be reached for comment.

“Novartis cannot currently fully exclude the possibility that traces of DMF (within acceptable limits) may have been present in materials” provided to their suppliers, said Novartis spokesman Eric Althoff in an email.

FDA is investigating the Valisure report at the moment. In the meantime these Valsartan had the highest levels of DMF;







Read more at Bloomberg

Hydrochlorothiazide A Diuretic, Or Water Pill, May Raise Skin Cancer Risk According To Health Canada.

A Health Canada's  recent report indicate that a high blood pressure medicine, hydrochlorothiazide  might trigger skin cancer. Hydrochlorothiazide and Valsartan were recalled in batches recently. More specifically, hydrochlorothiazide might increase the risks of non-melanoma skin cancer,

“Health Canada reviewed the best available evidence on the issue. Findings suggest an increased risk of non-melanoma skin cancer for patients who have used hydrochlorothiazide for more than three years. However, it is important to note that the studies reviewed had significant limitations. For example, there was a lack of patient data on sun exposure and the severity and duration of high blood pressure. Such data could help clarify the cause of the increased risk,” reported Health Canada.

Health Canada;
 

OTTAWA – Health Canada has completed a safety review of hydrochlorothiazide and has found that prolonged use of the drug could increase a person’s risk for non-melanoma skin cancer.

Hydrochlorothiazide is a prescription drug used to treat high blood pressure and swelling. It is known to make skin more sensitive to ultraviolet radiation and sunlight, meaning patients can get sunburned more easily.

Health Canada reviewed the best available evidence on the issue. Findings suggest an increased risk of non-melanoma skin cancer for patients who have used hydrochlorothiazide for more than three years. However, it is important to note that the studies reviewed had significant limitations. For example, there was a lack of patient data on sun exposure and severity, and duration of high blood pressure. Such data could help clarify the cause of the increased risk.

In light of these findings, Health Canada has concluded that prolonged use of hydrochlorothiazide may be associated with a risk of non-melanoma skin cancer that is at least four times the risk of not using hydrochlorothiazide.

Because of the seriousness of this risk and the wide use of this drug, Health Canada is taking a precautionary approach and is working with manufacturers to update the Canadian product safety information to reflect this new risk.

Health Canada will continue to monitor the safety of hydrochlorothiazide to identify and assess risks, as it does for all health products on the Canadian market. Health Canada will take appropriate and timely action if any new health risks are identified.

Important safety information for patients

• Talk to your healthcare provider or pharmacist if you are using hydrochlorothiazide and have any concerns regarding your risk for non-melanoma skin cancer.
• Inform your healthcare provider if you identify any new skin lesions, such as moles or changes to existing skin lesions.
• Limit your exposure to sunlight and avoid using tanning equipment as it can increase the risk of non-melanoma skin cancer. Use adequate protection when exposed to sunlight (e.g., sunscreen with SPF 30 or higher, clothing, and a hat).
• Talk to your healthcare provider if you think that you may be at a particularly higher risk for non-melanoma skin cancer (e.g., if you have light-coloured skin, if you have a personal or family history of skin cancer, or if you are receiving ongoing immunosuppressive therapy.).

Important information for healthcare providers:

• Research findings suggest an increased risk of non-melanoma skin cancer with prolonged use of hydrochlorothiazide. However, because of important limitations in the studies, substantial uncertainty remains regarding these findings.
• Patients taking hydrochlorothiazide should be informed of the risk of non-melanoma skin cancer. They should be advised to regularly check their skin for new lesions or changes to existing ones, and to report any suspicious skin lesions to their healthcare provider.
• Patients taking hydrochlorothiazide should be advised to limit exposure to sunlight, avoid using tanning equipment, and use adequate protection (e.g., sunscreen with SPF 30 or higher, clothing, and hat) when exposed to sunlight to minimize the risk of non-melanoma skin cancer.
• Alternatives to hydrochlorothiazide may be considered for patients who are at particularly higher risk for non-melanoma skin cancer (e.g., patients who have light-coloured skin, who have a personal or family history of skin cancer, or who are receiving ongoing immuno suppressive therapy).

Media enquiries

Health Canada
(613) 957-2983
hc.media.sc@canada.ca

Public enquiries

(613) 957-2991
1-866 225-0709

Recallr : Aurobindo Pharma USA, Inc. Initiates A Consumer Level Recall Amlodipine Valsartan Tablets USP, Valsartan HCTZ Tablets, USP and Valsartan Tablets USP

RecalsGlobal is reporting another Valsartan related recall. The current recall is by Aurobindo Pharma USA, Inc and it is a consumer level recall.
Read more about the 80 lots recalled and label photos (one such photo above) at Valsarten Reacall by Aurobindo Pharma USA, Inc at RecallsGlobal

FDA Issued A Warning Letter To Valsartan API Manufacturer, Zhejiang Huahai Pharmaceutical Co. Ltd. (ZHP)

 Looks like not only iPhone and plastic toys are manufactured in China these days. Recently recalled Valsartan's active pharmaceutical ingredient too was manufactured in China by Zhejiang Huahai Pharmaceutical Co. Ltd. (ZHP). FDA is currently investigating probable cancer-causing impurities found in certain commonly prescribed heart medicines. FDA's letter to Zhejiang Huahai Pharmaceutical Co. Ltd. outlines several manufacturing violations at company’s Chuannan facility, including impurity control, change control and cross contamination from one manufacturing process line to another.

 

The U.S. Food and Drug Administration today released a warning letter issued to Zhejiang Huahai Pharmaceutical Co. Ltd. (ZHP), in Linhai, Taizhou Zhejiang China, the manufacturer of the active pharmaceutical ingredient (API) found in valsartan that is the subject of an ongoing FDA investigation into probable cancer-causing impurities in certain commonly prescribed heart medicines. The letter outlines several manufacturing violations at ZHP’s Chuannan facility, including impurity control, change control and cross contamination from one manufacturing process line to another. The warning letter is another step forward in the ongoing investigation. The agency is still looking into the root cause of the impurity.

“We’re continuing to investigate and take action to protect patient health and safety from products in this angiotensin II receptor blocker class that have been found to have dangerous impurities. As part of that investigation, we’ve uncovered serious manufacturing violations at ZHP, which is one of the manufacturing facilities that has been linked to these products. The issues cited in the warning letter are associated with the nitrosamine impurities found in these drugs, and these violations reveal a disturbing lack of oversight at this API manufacturer that puts patients at risk,” said FDA Commissioner Scott Gottlieb, M.D.

The ZHP facility manufactures API including valsartan, a drug in the angiotensin II receptor blocker (ARB) class used to treat high blood pressure and heart failure. On September 28, the FDA also put this facility on import alert, stopping all API made there and finished drug products made using its API from legally entering the U.S. The agency put ZHP on import alert based, in part, on high levels of impurities found in ZHP’s API.

The FDA announced recalls of valsartan beginning in July due to the presence of N-Nitrosodimethylamine (NDMA) in API supplied by ZHP. Subsequent international investigations expanded to include all manufacturers of API and finished drugs in the ARB class and have resulted in additional recalls of valsartan, irbesartan, and losartan-containing products found to contain NDMA and N-Nitrosodiethylamine (NDEA) – both known animal and suspected human carcinogens.  

There may be confusion regarding which products are affected by ARB recalls and which are not, especially concerning the most recent U.S. recalls of valsartan-containing products using API manufactured by Mylan that tested positive for unacceptable levels of NDEA. Certain ARB products have been recalled, and certain products that contain ARBs and one or more other active ingredients in a single dosage form have been recalled. It is important to note that the API in these products besides valsartan, irbesartan or losartan are not necessarily under a recall. As an example, valsartan/amlodipine/hydrochlorothiazide is one product that has been recalled. Neither amlodipine or hydrochlorothiazide are currently under recall. Similarly, losartan potassium and hydrochlorothiazide 100mg/25mg is a recalledproduct. The agency asks the public to pay careful attention to the agency’s website for the most accurate and up-to-date information. The agency’s website provides lists of valsartan products under recall, valsartan products not under recall and irbesartan products under recall for patients, health care providers and pharmacists to accurately confirm which products are affected.

The FDA continues to test all ARBs for the presence of impurities and has publicly posted two methods for manufacturers and regulatory agencies around the world to test their ARBs for the unexpected NDMA and NDEA impurities.

Patients taking any recalled ARB should continue taking their current medicine until their pharmacist provides a replacement or their doctor provides an alternative treatment option. It also is important to know that not all ARBs contain NDMA or NDEA, so pharmacists may be able to provide a refill of medication not affected by the recall, or doctors may prescribe a different medication that treats the same condition.

Patients, health care providers and pharmacists may contact the FDA’s Division of Drug Information for any questions regarding ARB recalls. Visit the FDA’s ARB recall webpage, call 855-543-3784 or email druginfo@fda.hhs.gov for more information. A question and answer webpage also provides information on these recalls.