Mega Doctor News
Recalls of Angiotensin II Receptor Blockers (ARBs) including Valsartan, Losartan and Irbesartan
What you should know about this recall
What are valsartan, losartan, and irbesartan?
Valsartan, losartan, irbesartan and other “-sartan” drugs are a class of medicines known as angiotensin II receptor blocker (ARBs) used to treat high blood pressure and heart failure.
Why are some valsartan, losartan, and irbesartan medicines being recalled?
Beginning in Summer 2018, FDA learned and reported that some generic versions of the angiotensin II receptor blocker (ARB) medicines contain nitrosamine impurities that don’t meet the agency’s safety standards.
- Nitrosamine impurities, including N-Nitrosodimethylamine (NDMA), and N-Nitrosodiethylamine (NDEA), are probable human carcinogens (a substance that could cause cancer), and N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) is a potential human carcinogen.
- Nitrosamines are known environmental contaminants and found in water and foods, including meats, dairy products and vegetables.
- The presence of these nitrosamine impurities in ARB medicines was unexpected. Our ongoing effort has determined that these impurities may be generated when specific chemicals and reaction conditions are present in the manufacturing process of the drug’s API, and may also result from the reuse of materials, such as solvents.
Which ARB medications are being recalled?
Not all valsartan, losartan, and irbesartan-containing medications are affected and being recalled.
Not all lots of valsartan, irbesartan, and losartan from a manufacturer involved in a recall are affected and being recalled. FDA has posted a list of currently available ARBs and the status of our assessment of those medications.
Medications containing only amlodipine or hydrochlorothiazide (HCTZ) are not being recalled.
Some manufacturers are recalling some medications containing amlodipine in combination with valsartan or losartan, and some medications containing hydrochlorothiazide HCTZ in combination with valsartan or losartan are also being recalled.
To find out if your medication has been recalled, you need the following information:
- Manufacturer or labeler name
- National Drug Code (NDC)
- Lot number
- Active ingredient(s)
Why didn’t FDA identify the risk of these impurities earlier?
We review information on impurity testing provided in drug applications and when inspecting manufacturing facilities.
Manufacturers are required to test for impurities that may be introduced or developed during their manufacturing processes.
We review that information in drug applications, including requests to change the manufacturing process.
We employ organic chemists to review applications and referenced information to look for steps – and manufacturing changes – where these risks could be introduced.
We also inspect manufacturing facilities around the world, and in routine current good manufacturing practices inspections we can review a manufacturer’s records regarding impurity testing.
However, the review of records depends on manufacturers conducting appropriate tests that are capable of detecting the impurity.
Tests are selected based on assessments of what impurities may develop based on the manufacturing process.
In other words, it needs to be recognized that there is a risk of an impurity occurring to know that it should be tested for.
Before we undertook this analysis, neither regulators nor industry fully understood how the nitrosamines could form during the manufacturing process.
Where do I find the manufacturer or repackager name and National Drug Code (NDC) of my medication?
Following is an example of an ARB medication label to help you identify the information on your medication:
Note the manufacturer may be different from the distributor or labeler of your medication. Learn more about the NDC.
Contact your pharmacist to get this information if you cannot find it or if you have questions about your medication being recalled.
Where do I find the lot number of my medication?
If the lot number is on the medication bottle, it is usually imprinted on the label and is normally found next to the expiration date. It will also be printed on the back of a blister pack.
Contact your pharmacist to get this information if you cannot find it or if you have questions about your medication being recalled.
What is the risk to patients who have taken the affected product?
NDMA was the first impurity discovered, and FDA pharmacologists, toxicologists and chemists have taken measures to assess its risk.
Our scientists estimate that if 8,000 people took the highest daily valsartan dose (320 mg) that contained NDMA for four years (the amount of time we believed the affected products had been on the U.S. market), there may be one additional case of cancer beyond the average cancer rate among Americans.
Most patients who were exposed to the impurity through the use of affected valsartan received less exposure than in the scenario described above.
Since there are many manufacturers of valsartan and sources can vary whenever a patient refills a prescription, it is very likely that a patient using valsartan for four years would not have always received one of the relatively few affected medicines that contained these impurities.
We are still seeking to similarly quantify the risk to patients from NDEA and will communicate our findings as soon as possible.
Should I continue taking my medication even if it has been recalled?
Yes. Because ARBs treat serious medical conditions, continue taking your current medicine until a doctor or pharmacist gives you a replacement or a different treatment option.
Remember, not all ARBs are being recalled, and not all lots of valsartan, irbesartan, and losartan are affected and being recalled.
If you are taking any medication containing an ARB, compare the information on your prescription bottle with the recall list to determine if your current medicine has been recalled.
- If you have medicine included in a recall, contact your pharmacist. The pharmacist may be able to provide you with an unaffected ARB made by another company.
- If the pharmacist cannot provide this, contact your doctor to discuss other treatment options.
Report any unexpected side effects with ARB-containing medicines, to FDA’s MedWatch program to help the agency better understand the scope of the problem:
- Complete and submit the report online at www.fda.gov/medwatch/report.htm
- Download and complete the appropriate form, then submit it via fax at 1-800-FDA-0178
What is FDA doing to ensure all affected products are quickly removed from the market?
We are working with manufacturers to recall medicines with nitrosamine impurities above the interim acceptable intake levels that present an unnecessary risk to patients.
Lists of ARB medicines affected by the recall are available on FDA’s website for healthcare professionals and patients to monitor.
We will update our website if any other medicines are recalled due to these impurities.
We are also working with makers of API to ensure they remediate their manufacturing processes and their API does not contain these impurities.
What do I do with my unused medication?
Return it to your pharmacist when you get your new medication.
What should I know as a health care professional?
FDA has determined the recalled ARBs pose an unnecessary risk to patients.
FDA recommends that pharmacists provide a replacement medicine not affected by the recall or prescribers consider other available treatment options for their patient’s medical condition.
A list of ARB medications affected by the recall are available on FDA’s website for healthcare professionals and patients to monitor. FDA has also posted a list of ARBs that are currently available, along with information regarding the status of FDA’s assessment for those medications.
FDA suggests health care professionals check the lists regularly for updates.
Samples can also be affected and part of the recall. Be certain to check samples to ensure affected products are not given to patients.
- If you have medication samples from these companies, quarantine the products, and do not provide them to patients.
Report any adverse reactions with ARB-containing products, to FDA’s MedWatch program to help the agency better understand the scope of the problem:
- Complete and submit the report online at www.fda.gov/medwatch/report.htm
- Download and complete the appropriate form, then submit it via fax at 1-800-FDA-0178
How do I find out more information?
FDA’s website contains the most current information about the affected products.
Please send us questions or comments by email to druginfo@FDA.hhs.gov or by phone to 855-543-3784.
Patients and health care professionals should report any unexpected adverse event with ARB-containing products to the FDA’s MedWatch program to help the agency better understand the scope of the problem:
- Complete and submit the report online at www.FDA.gov/medwatch/report.htm or
- Download and complete the appropriate form, then submit it via fax at 1-800-FDA-0178.
Resources for You
Information Source: FDA
