Fda Expands Blood Pressuredrug Recall

Update: eleven/xiii/2019 - FDA warns Mylan for CGMP deviations

Update [11/13/2019] Today, the U.S. Food and Drug Administration posted a alert letter to Mylan Pharmaceuticals, Inc. in Chodavaram Village, Vizianagaram, Andhra Pradesh, Republic of india. Mylan manufactures valsartan agile pharmaceutical ingredient (API) and has been i field of study of an ongoing global investigation into nitrosamine impurities in angiotensin II receptor blockers (ARBs) such as valsartan, losartan and irbesartan.

The warning letter outlines several current good manufacturing practice (CGMP) deviations at this Mylan facility, including failure to have acceptable written procedures for the receipt, identification and handling of raw materials and failure to adequately clean equipment and utensils. Failure to correct these deviations may result in further activeness by the agency. The alarm letter is another result of the bureau's ongoing investigation.

FDA reminds patients taking recalled ARBs to continue taking their current medicine until their pharmacist provides a replacement or their doctor prescribes a different medication that treats the aforementioned condition.

Update: ten/15/2019 - FDA warns Torrent for CGMP violations

Update [10/15/2019] Today, the U.S. Food and Drug Administration posted a warning letter to Torrent Pharmaceuticals in Ahmedabad, Gujarat, India. Torrent manufactures losartan potassium tablets and has been one subject of an ongoing global investigation into nitrosamine impurities in angiotensin Two receptor blockers (ARBs) such as valsartan, losartan and irbesartan.

The alarm letter outlines several manufacturing violations at Torrent's Taluka-Kadi, Indrad, Gujarat facility, including failure to follow written procedures for production and process command and failure to adequately investigate batch discrepancies. Failure to correct these violations may result in farther action by the agency. The warning letter is another outcome of the agency'southward ongoing investigation.

FDA reminds patients taking recalled ARBs to continue taking their current medicine until their pharmacist provides a replacement or their md prescribes a unlike medication that treats the same condition.

Update: 9/20/2019 - Torrent expands its voluntary recall of losartan

Update [9/20/2019] Torrent Pharmaceuticals is expanding its voluntary recall to include five boosted lots of losartan potassium tablets (three lots of losartan potassium tablets and two lots of losartan potassium/hydrochlorothiazide (HCTZ) combination tablets). This recall is due to unacceptable amounts of N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) in the losartan active pharmaceutical ingredient manufactured by Hetero Labs Limited. Torrent is recalling lots of losartan-containing medication that tested positive for NMBA higher up 9.82 parts per million.

The agency updated the list of recalled angiotensin Two receptor blockers (ARBs) appropriately.

FDA reminds patients taking recalled ARBs to go along taking their current medicine until their pharmacist provides a replacement or their doctor prescribes a dissimilar medication that treats the same status.

6/26/2019: UPDATE - Macleods Pharmaceuticals voluntarily recalls losartan containing NMBA

Update [6/26/2019] FDA is alerting patients and wellness care professionals to Macleods Pharmaceuticals' voluntary recall of 2 lots of losartan potassium tablets (50mg strength) and 30 lots of losartan potassium/hydrochlorothiazide (HCTZ) combination tablets (12 lots of 50mg/12.5mg strength, iii lots of 100mg/12.5mg strength, and 15 lots of 100mg/25mg strength). This recall is due to unacceptable amounts of Due north-Nitroso-N-methyl-4-aminobutyric acid (NMBA) in the losartan agile pharmaceutical ingredient (API) manufactured past Hetero Labs Limited.

FDA is working with manufacturers to reduce and remove nitrosamines from angiotensin 2 receptor blockers (ARBs). The agency as well updated the list of recalled angiotensin 2 receptor blockers (ARBs) .

FDA reminds patients taking recalled ARBs to go along taking their current medicine until their pharmacist provides a replacement or their md prescribes a different medication that treats the aforementioned condition.

6/12/2019: UPDATE - Teva expands its voluntary recall of losartan

Update [half dozen/12/2019] Teva Pharmaceuticals is expanding its voluntary recall to include seven additional lots of losartan potassium tablets (three lots of l mg strength and four lots of 100 mg strength) labeled past Golden Land Medical Supply. This recall is due to unacceptable amounts of N-Nitroso-N-methyl-4-aminobutyric acid (NMBA) in the losartan agile pharmaceutical ingredient (API) manufactured by Hetero Labs Limited. Teva is recalling lots of losartan-containing medication that tested positive for NMBA above nine.82 parts per one thousand thousand.

The bureau updated the list of recalled angiotensin II receptor blockers (ARBs) accordingly.

FDA reminds patients taking recalled ARBs to continue taking their electric current medicine until their chemist provides a replacement or their doctor prescribes a dissimilar medication that treats the same condition.

v/half dozen/2019: UPDATE - FDA alerts patients and wellness care professionals to Vivimed'southward retrieve of losartan medication due to NMBA

Update [v/six/2019] FDA is alerting patients and health care professionals to a voluntary remember of 19 lots of losartan potassium tablets fabricated by Vivimed Life Sciences Pvt Ltd in Alathur, Chennai, Republic of india and distributed by Heritage Pharmaceuticals Inc, East Brunswick, New Jersey, due to the detection of the impurity North-Nitroso-N-methyl-iv-aminobutyric acid (NMBA). Vivimed is recalling lots of losartan-containing medication that tested positive for NMBA above 9.82 parts per million.

Manufacturers should contact FDA's Drug Shortages Staff when their testing of losartan shows levels of NMBA that exceed the acting adequate intake limit of 0.96 ppm. FDA will determine, on a case-by-example basis, whether lots containing NMBA greater than 0.96 ppm should be released for distribution.

FDA reminds patients taking recalled angiotensin Two receptor blockers (ARBs) to keep taking their current medicine until their pharmacist provides a replacement or their doctor prescribes a unlike medication that treats the same condition.

The agency likewise updated the listing of recalled ARBs.

4/29/2019: UPDATE - FDA alerts patients and health care professionals to Teva'southward recall and Legacy'due south expanded recall of losartan medication due to NMBA

Update [4/29/2019] FDA is alerting patients and health care professionals to a voluntary call up of 44 lots of losartan potassium tablets manufactured by Teva Pharmaceuticals and labeled as Aureate State Medical Supply due to the detection of the impurity Northward-Nitroso-North-methyl-4-aminobutyric acid (NMBA). The recalled products were made with active pharmaceutical ingredient (API) manufactured by Hetero Labs. Teva is recalling lots of losartan-containing medication that tested positive for NMBA higher up 9.82 parts per million.

Additionally, Legacy expanded its call back to include one additional lot of losartan tablets made with API manufactured past Hetero Labs.

Manufacturers should contact FDA'south Drug Shortages Staff when their testing of losartan shows levels of NMBA that exceed the interim acceptable intake limit of 0.96 ppm. FDA volition determine, on a case-by-case basis, whether lots containing NMBA greater than 0.96 ppm should exist released for distribution.

The agency also updated the listing of recalled losartan medicines.

iv/nineteen/2019: UPDATE - Torrent further expands its voluntary call back of losartan; FDA posts new nitrosamine testing methods

Update [4/19/2019] Torrent Pharmaceuticals Limited is farther expanding its voluntary remember to include 104 additional lots of losartan potassium and losartan potassium/hydrochlorothiazide combination tablets. This think is due to unacceptable amounts of Northward-Nitroso-N-methyl-iv-aminobutyric acid (NMBA) in the losartan active pharmaceutical ingredient (API) manufactured past Hetero Labs Limited.

The agency updated the list of losartan products under call back accordingly.

FDA reminds patients taking recalled angiotensin II receptor blockers (ARBs) to continue taking their current medicine until their pharmacist provides a replacement or their md prescribes a different medication that treats the aforementioned condition.

FDA is also posting new testing methods which can assistance manufacturers and international regulators detect and identify multiple nitrosamine impurities. FDA and international regulators take identified N-Nitrosodimethylamine (NDMA), Northward-Nitrosodiethylamine (NDEA) and NMBA in ARBs.

• A directly injection GC-MS method that is able to detect NDMA, NDEA, N-Nitrosodiisopropylamine (NDIPA), Northward-Nitrosoethylisopropylamine (NEIPA), and N-nitrosodibutylamine (NDBA)
• A headspace GC-MS method that is able to detect NDMA, NDEA, NDIPA, and NEIPA

These methods should exist validated by the user if the resulting data are used to support a required quality cess of the API or drug product, or if the results are used in a regulatory submission.

3/20/2019: UPDATE - FDA non objecting to losartan with NMBA beneath 9.82 ppm remaining on the market place

Update [three/20/2019] To ensure patient admission to losartan, FDA volition non object to sure manufacturers temporarily distributing losartan containing Northward-Nitroso-North-methyl-4-aminobutyric acid (NMBA) above the acting acceptable intake limit of 0.96 parts per 1000000 (ppm) and below 9.82 ppm until the impurity can be eliminated. The bureau expects many companies will be able to manufacture losartan without nitrosamine impurities and replenish the U.S. supply in approximately 6 months.

Agency scientists evaluated the run a risk of exposure to NMBA at levels up to ix.82 ppm and determined that information technology presents no meaningful difference in cancer gamble over a half-dozen-month time flow when compared to a lifetime of exposure to NMBA at 0.96 ppm. Distributing losartan containing NMBA up to 9.82 ppm, will help maintain adequate losartan supply while companies obtain approval for manufacturing processes that produce nitrosamine-free losartan for patients.

FDA reminds patients taking recalled losartan to go on taking their current medicine until their pharmacist provides a replacement or their doctor prescribes a unlike medication that treats the same condition. Untreated hypertension (high claret pressure) leads to an increase in the risk of heart attacks and stroke. Untreated eye failure increases the risk of hospitalization and death. Untreated diabetic nephropathy (kidney affliction) leads to worsening renal (kidney) disease.

Manufacturers should contact FDA'south Drug Shortages Staff when their testing of losartan shows levels of NMBA that exceed the interim acceptable intake limit of 0.96 ppm. FDA will determine, on a instance-by-case ground, whether lots containing NMBA greater than 0.96 ppm should be released for distribution.

FDA continues to piece of work with companies and international regulators to ensure products entering the U.S. market place do non contain nitrosamine impurities.

three/1/2019: UPDATE - Torrent again expands its voluntary think of losartan; Hetero too voluntarily recalls losartan

Update [iii/1/2019] Torrent Pharmaceuticals Limited is further expanding its voluntary recall to include 114 boosted lots of losartan potassium and losartan potassium/hydrochlorothiazide combination tablets. This recall is due to unacceptable amounts of Northward-Nitroso-N-methyl-4-aminobutyric acrid (NMBA) in the losartan agile pharmaceutical ingredient manufactured by Hetero Labs Express.

Today, the agency also issued a printing release to provide additional information virtually its ongoing investigation and another voluntary recall past Hetero/Slant Pharmaceuticals, which was announced on Feb 28, of 87 lots of losartan potassium tablets (25 mg, fifty mg and 100 mg). The recalled losartan potassium and losartan potassium/hydrochlorothiazide tablets are too manufactured by Hetero, which are distributed by Camber, and comprise the impurity NMBA.

Torrent and Hetero/Camber are merely recalling lots of losartan-containing medication with NMBA higher up the interim acceptable intake limits of 0.96 parts per million (ppm).

The agency also updated the list of losartan products under recall.

3/1/2019: UPDATE - Aurobindo expands its voluntary recall of valsartan and amlodipine/valsartan

Update [3/1/2019] AurobindoPharma USA is expanding its voluntary recall to include 38 additional lots of valsartan and amlodipine/valsartan combination tablets. The remember is due to unacceptable amounts of N-Nitrosodiethylamine (NDEA) establish in the medicine.

Aurobindo is only recalling lots of valsartan-containing medication where NDEA has been detected above the interim acceptable intake limit of 0.083 parts per 1000000. FDA is working with manufacturers to reduce and remove nitrosamines from angiotensin II receptor blockers (ARBs).

The bureau as well updated the valsartan products nether think.

FDA updates table of interim limits for nitrosamine impurities in ARBs

Update [2/28/2019] FDA is posting the updated table of acting acceptable intake limits for nitrosamine impurities to reverberate N-Nitroso-Northward-methyl-4-aminobutyric acid (NMBA) limits, which are the same equally those for NDMA.

The agency will employ the interim limits below to recommend manufacturers bear a voluntary recall if laboratory testing confirms the presence of nitrosamine impurities in finished drug product. FDA is working with industry and international regulators to ensure products entering the market practice not contain these impurities, just we are tolerating the impurities below the level established in the table for a short flow of time to avoid a possible shortage of ARBs.

Not all ARB products contain NDMA, NDEA or NMBA impurities, and so pharmacists may exist able to provide an alternative medication not afflicted by the recalls, or wellness care professionals may prescribe a dissimilar medication that treats the same status.

Interim Limits for NDMA, NDEA, and NMBA in Angiotensin Two Receptor Blockers (ARBs)

Drug	Maximum Daily Dose (mg/day)	Acceptable Intake NDMA (ng/day)*	Acceptable Intake NDMA (ppm)**	Acceptable Intake NDEA (ng/day)*	Acceptable Intake NDEA (ppm)**	Adequate Intake NMBA (ng/day)*	Acceptable Intake NMBA (ppm)**
Valsartan	320	96	0.3	26.v	0.083	96	0.3
Losartan	100	96	0.96	26.5	0.27	96	0.96***
Irbesartan	300	96	0.32	26.v	0.088	96	0.32
Azilsartan	80	96	1.2	26.v	0.33	96	1.two
Olmesartan	xl	96	2.4	26.v	0.66	96	2.four
Eprosartan	800	96	0.12	26.v	0.033	96	0.12
Candesartan	32	96	3.0	26.v	0.83	96	3.0
Telmisartan	fourscore	96	one.2	26.5	0.33	96	1.two

* The acceptable intake is a daily exposure to a chemical compound such equally NDMA, NDEA, or NMBA that approximates a 1:100,000 cancer hazard after 70 years exposure
** These values are based on a drug'due south maximum daily dose equally reflected in the drug label
*** FDA is temporarily not objecting to losartan with NMBA below 9.82 ppm remaining on the market

2/25/2019: UPDATE - Losartan distributed by Macleods Pharmaceuticals voluntarily recalled

Update [2/25/2019] FDA is alerting patients and health care professionals to a voluntary recall of one lot of losartan potassium/hydrochlorothiazide (HCTZ) 100mg/25mg combination tablets manufactured by Macleods Pharmaceuticals. The recall is due to unacceptable amounts of North-Nitrosodiethylamine (NDEA) found in the medicine fabricated with active pharmaceutical ingredient manufactured by Hetero Labs Limited.

Macleods is only recalling lots of losartan-containing medication where NDEA has been detected in a higher place the interim acceptable intake limit of 0.27 parts per million. FDA is working with manufacturers to reduce and remove nitrosamines from angiotensin Two receptor blockers (ARBs).

The agency also updated the listing of losartan products under recall.

one/23/2019: UPDATE - Torrent further expands its voluntary recall of losartan

Update [1/23/2019] Torrent Pharmaceuticals is farther expanding its voluntary recall to include six additional lots of losartan potassium and hydrochlorothiazide combination tablets, for a full of 16 lots of losartan-containing medicines. This call up is due to unacceptable amounts of Northward-Nitrosodiethylamine (NDEA) in the losartan active pharmaceutical ingredient manufactured by Hetero Labs Limited.

Torrent is merely recalling lots of losartan-containing medication containing NDEA above the interim acceptable intake limits of 0.27 parts per meg (ppm).

The agency also updated the list of losartan medications under recall.

1/18/2019: UPDATE - Irbesartan distributed past Solco Healthcare voluntarily recalled

Update [one/eighteen/2019] FDA is alerting patients and wellness care professionals to a voluntary recall of one lot of irbesartan and seven lots of irbesartan and hydrochlorothiazide (HCTZ) combination tablets distributed by Solco Healthcare LLC, a Prinston Pharmaceutical Inc. subsidiary. The recall is due to unacceptable amounts of Northward-Nitrosodiethylamine (NDEA) in the irbesartan active pharmaceutical ingredient manufactured by Zhejiang Huahai Pharmaceuticals (ZHP).

Solco is just recalling lots of irbesartan-containing medication where NDEA has been detected above the interim limit of 0.088 parts per million. FDA is working with manufacturers to reduce and remove nitrosamines from angiotensin receptor II blockers (ARBs).

The agency also updated the list of irbesartan products under call up.

ane/iii/2019: UPDATE - Torrent expands its voluntary recall of losartan

Update [1/iii/2019] Torrent Pharmaceuticals is expanding its voluntary call up to include eight additional lots of losartan potassium tablets, for a total of 10 lots. This recall is due to trace amounts of N-Nitrosodiethylamine (NDEA) in the losartan active pharmaceutical ingredient (API) manufactured past Hetero Labs Limited.

Torrent is simply recalling lots of losartan medication containing NDEA above the interim acceptable intake level of 0.27 parts per million.

The agency also updated the list of list of valsartan products under recall.

1/2/2019: UPDATE - FDA alerts patients and health care professionals to Aurobindo's recall of valsartan medication due to NDEA

Update [1/2/2019] FDA is alerting patients and health care professionals to Aurobindo Pharma Us'south voluntary recall of two lots of valsartan tablets, 26 lots of amlodipine and valsartan combination tablets, and 52 lots of valsartan and hydrochlorothiazide (HCTZ) combination tablets due to the amount of N-Nitrosodiethylamine (NDEA) in the valsartan active pharmaceutical ingredient. Aurobindo is recalling amlodipine and HCTZ only in combination medications containing valsartan. Neither amlodipine nor HCTZ is currently under recall past itself.

Aurobindo is recalling lots of valsartan-containing medication that tested positive for NDEA above the acting acceptable daily intake level of 0.083 parts per meg.

The bureau continues to investigate and examination all angiotensin II receptor blockers (ARBs) for the presence of NDEA and Northward-Nitrosodimethylamine (NDMA) and is taking swift action when it identifies these impurities that are above acting acceptable daily intake levels.

FDA as well updated the list of valsartan products under recall and the list of valsartan products not nether recall.

FDA reminds patients taking whatever recalled ARB to go along taking their electric current medicine until their pharmacist provides a replacement or their doctor prescribes a different medication that treats the same condition. Some ARBs contain no NDMA or NDEA.

12/20/2019: UPDATE - FDA alerts patients and health care professionals to Torrent'due south recall of losartan medication due to NDEA

Update [12/20/2018] FDA is alerting patients and health care professionals to Torrent Pharmaceuticals'
voluntary recall of two lots of losartan potassium 100 mg tablets due to N-Nitrosodiethylamine (NDEA) in the losartan active pharmaceutical ingredient (API) manufactured by Hetero Labs Limited.

Not all Torrent losartan-containing medications distributed in the U.S. are being recalled. Torrent is recalling simply those lots of losartan medication that tested positive for NDEA above the adequate daily intake of 0.27 ppm.

The agency continues to investigate and exam all angiotensin II receptor blockers (ARBs) for the presence of NDEA and N-Nitrosodimethylamine (NDMA) and is taking swift action when information technology identifies these impurities that are to a higher place acceptable daily intake levels.

FDA posted a listing of losartan medications under recall. Additionally, FDA reminds patients taking this medication or whatsoever recalled ARB to continue taking their current medicine until their chemist provides a replacement or their dr. provides an culling treatment pick. Information technology likewise is important to know not all ARBs comprise NDMA or NDEA, so pharmacists may be able to provide a refill of medication not affected by the remember, or doctors may prescribe a different medication that treats the aforementioned condition.

12/19/2018: UPDATE - FDA presents interim limits of nitrosamines in currently marketed ARBs

Update [12/19/2018] FDA is publishing interim acceptable intake levels of nitrosamine impurities in angiotensin II receptor blockers (ARBs) for manufacturers to use to ensure their finished drug products are safe for patients.

The bureau evaluated safety data for N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) to determine an interim acceptable intake level for these impurities in the ARB class. NDMA and NDEA are probable human carcinogens and should not be present in drug products. We are currently aware of NDMA and NDEA in sure valsartan, irbesartan and losartan-containing products, and those products and some agile pharmaceutical ingredients (API) used to manufacture them accept been recalled from the U.S. market. See the list of valsartan products under remember and the listing of irbesartan products under recall.

Drug products that incorporate NDMA or NDEA above the limits in the table below pose an unacceptable risk to patients. The agency will employ the interim limits to recommend manufacturers conduct a voluntary recall if laboratory testing confirms the presence of nitrosamine impurities in finished drug production. FDA is working with manufacture and international regulators to ensure products entering the market place do not contain these impurities, but nosotros are tolerating the impurities below the level established in the table for a short menstruation of time to avoid a possible shortage of ARBs.

The bureau reminds manufacturers they are responsible for developing and using suitable methods to observe impurities, including when they brand changes to their manufacturing processes. If a manufacturer detects a new impurity or higher level of impurities, they should fully evaluate the impurities and take action to ensure the production is prophylactic for patients. To assist manufacture and regulatory agencies, FDA has developed and published methods to detect NDMA and NDEA impurities – the gas chromatography/mass spectrometry (GC/MS) headspace method, the combined GC/MS headspace method, and the combined GC/MS straight injection method. These methods tin be used for drug substances and products, and users should validate them as part of good manufacturing practices and where data are used to back up a regulatory submission or required quality assessment of the API or drug product.

Non all ARB products incorporate NDMA or NDEA impurities, and then pharmacists may exist able to provide an culling medication not affected by the recalls, or health care professionals may prescribe a different medication that treats the same condition.

Interim Limits for NDMA and NDEA in Angiotensin Two Receptor Blockers (ARBs)

Drug	Maximum Daily Dose (mg/day)	Adequate Intake NDMA (ng/day)*	Acceptable Intake NDMA (ppm)**	Acceptable Intake NDEA (ng/twenty-four hour period)*	Acceptable Intake NDEA (ppm)**
Valsartan	320	96	0.iii	26.five	0.083
Losartan	100	96	0.96	26.5	0.27
Irbesartan	300	96	0.32	26.v	0.088
Azilsartan	80	96	1.two	26.5	0.33
Olmesartan	40	96	2.4	26.five	0.66
Eprosartan	800	96	0.12	26.5	0.033
Candesartan	32	96	3.0	26.5	0.83
Telmisartan	80	96	1.2	26.five	0.33

* The adequate intake is a daily exposure to a compound such as NDMA or NDEA that results in a i:100,000 cancer
take chances later on 70 years exposure
** These values are based on a drug's maximum daily dose every bit reflected in the drug label

For comparison with the levels of NDMA establish in some mutual foods, please run across our Aug. 20, 2018, update.

12/12/2018: UPDATE - FDA updates NDMA and NDEA detection methods, announces posting of ZHP alarm letter of the alphabet

Update [12/12/2018] The FDA has updated its testing methods to notice NDMA and NDEA impurities – the (GC/MS) headspace method, the combined headspace method, and the combined straight injection method – by adding the limits of detection (LOD) and clarifying that the methods can be used for both drug substances and drug products. These methods were validated with respect to valsartan drug substances and drug products, only the agency expects them to accept comparable LODs and limits of quantitation (LOQ) for other angiotensin Two receptor blockers (ARB).

The agency too issued a press release announcing the posting of a warning letter the agency issued November. 29 to Zhejiang Huahai Pharmaceuticals Co. Ltd. (ZHP).

12/6/2018: UPDATE - Mylan expands its voluntary call up of valsartan-containing products

Update [12/6/2018] Mylan Pharmaceuticals is expanding its voluntary recall to include all lots of non-expired valsartan-containing products due to trace amounts of Due north-Nitrosodiethylamine (NDEA) in the valsartan agile pharmaceutical ingredient (API) manufactured by Mylan Laboratories Limited. The 104 additional lots include 26 lots of amlodipine and valsartan tablets, 51 lots of valsartan tablets and 27 lots of valsartan and hydrochlorothiazide tablets. These lots were distributed in the U.S. betwixt March 2017 and November 2018.

The agency likewise updated the list of valsartan products under remember and the list of valsartan products not under recollect.

11/27/2018: UPDATE - FDA alerts patients and health care professionals to Teva's remember of valsartan products due to NDEA

Update [11/27/2018] FDA is alerting patients and health care professionals to Teva Pharmaceuticals' voluntary remember of valsartan-containing products manufactured using agile pharmaceutical ingredient (API) from Mylan Pharmaceuticals. Mylan voluntarily recalled valsartan-containing products on November xx.

Teva is recalling all lots of amlodipine and valsartan combination tablets and amlodipine, valsartan, and hydrochlorothiazide (HCTZ) combination tablets due to the presence of N-Nitrosodiethylamine (NDEA). Teva has recalled other valsartan-containing products in recent months due to the presence of N-Nitrosodimethylamine (NDMA). With this recall, Teva has now recalled all their unexpired valsartan-containing products from the U.South. market place.

The agency continues to investigate and test all angiotensin 2 receptor blocker (ARBs) for the presence of NDMA and NDEA and is taking swift action when it identifies these impurities that are above acceptable levels.

FDA has updated the list of valsartan products under think and the listing of valsartan products non under recall. The agency reminds patients taking this medication or any recalled ARB to continue taking their electric current medicine until their pharmacist provides a replacement or their doctor provides an culling treatment option. It besides 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 call up, or doctors may prescribe a different medication that treats the same condition.

eleven/21/2018: UPDATE - FDA alerts patients and health intendance professionals to Mylan's recall of valsartan products due to NDEA

Update [11/21/2018] FDA is alerting patients and health care professionals to Mylan Pharmaceuticals' voluntary recall of xv lots of valsartan-containing products due to the presence of Due north-Nitrosodiethylamine (NDEA).

Not all Mylan valsartan-containing products distributed in the U.S. are existence recalled. Mylan is recalling only those lots of valsartan-containing products that tested positive for NDEA above the acceptable level. The bureau continues to investigate and examination all angiotensin 2 receptor blockers (ARBs) for the presence of NDEA and N-Nitrosodimethylamine (NDMA) and is taking swift action when information technology identifies these impurities that are above acceptable levels.

FDA has updated lists of valsartan products nether recall and valsartan products not under recall. Additionally, FDA reminds patients taking this medication or any recalled ARB to continue taking their current medicine until their pharmacist provides a replacement or their doctor provides an alternative treatment pick. It besides is important to know not all ARBs contain NDMA or NDEA, and so pharmacists may be able to provide a refill of medication not afflicted by the recollect, or doctors may prescribe a different medication that treats the same condition.

11/9/2018: UPDATE - FDA alerts patients and health intendance professionals to Sandoz'southward losartan potassium and hydrochlorothiazide recall of one lot due to NDEA

Update [11/9/2018] FDA is alerting patients and health care professionals to Sandoz's voluntary recall of one lot – JB8912 – of losartan potassium and hydrochlorothiazide 100mg/25mg tablets, that incorporate losartan, an angiotensin Two receptor blocker (ARB), and hydrochlorothiazide, a diuretic, used in combination for the treatment of hypertension. Sandoz's product was made using an active pharmaceutical ingredient (API) that has tested positive for NDEA. The API was manufactured by Zhejiang Huahai Pharmaceutical Co. Ltd, which is on import alarm.

Sandoz's losartan drug products make up less than 1 percentage of the full losartan drug products in the U.S. market.

FDA continues to investigate the presence of NDEA and NDMA, which are probable human carcinogens, in ARBs and is taking swift action when it identifies unacceptable impurities in API and finished drug products.

FDA reminds patients taking this medication or whatsoever recalled ARB to continue taking their electric current medicine until their pharmacist provides a replacement or their doctor provides an alternative treatment pick. Information technology also is important to know not all ARBs contain NDEA or NDMA, and then pharmacists may be able to provide a refill of medication non affected by the recall, or doctors may prescribe a different medication that treats the same condition.

10/30/2018: UPDATE - FDA alerts patients and health intendance professionals to ScieGen's irbesartan recall due to NDEA

Certain irbesartan products labeled as Westminster Pharmaceuticals Inc. and GSMS Inc. recalled

Update [10/xxx/2018] FDA is alerting patients and health intendance professionals to ScieGen'southward voluntary recall of certain lots of irbesartan, an angiotensin II receptor blocker (ARB), because they comprise N-Nitrosodiethylamine (NDEA), a known animal and suspected human carcinogen (causes cancer). FDA laboratory testing confirmed NDEA in some lots of ScieGen'due south irbesartan. ScieGen'southward irbesartan products are labeled as Westminster Pharmaceuticals and Golden Land Medical Supply, Inc. (GSMS). Meet the listing of irbesartan products nether recall. This is the first non-valsartan drug product the agency has found to contain the NDEA impurity.

ScieGen's recall affects about one percent of the irbesartan drug products in the U.S. market.

Additionally, Aurobindo, which manufactures the active pharmaceutical ingredient (API) for ScieGen'due south irbesartan products, is recalling all unexpired lots of its irbesartan API supplied to the U.S. market with NDEA. FDA and Aurobindo laboratory testing confirmed NDEA in certain lots of their irbesartan API.

FDA reminds patients taking any recalled ARB to proceed taking their current medicine until their pharmacist provides a replacement or their dr. provides an alternative treatment option. Non all ARBs contain NDEA or N-Nitrosodimethylamine (NDMA), a likely human carcinogen previously found in sure recalled valsartan products, and so pharmacists may be able to provide a refill of medication not afflicted past the think, or doctors may prescribe a unlike medication that treats the same condition.

To date, ScieGen is the only manufacturer of irbesartan drug products found to contain NDEA. 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. The combined headspace method and the combined direct injection method can detect and quantify NDMA and NDEA simultaneously in ARB API and finished drug products.

FDA continues to work with API and drug manufacturers to ensure their products are not at risk for NDMA or NDEA formation. The bureau reminds manufacturers they are responsible for developing and using suitable methods to observe impurities, including when they make changes to their manufacturing processes. If a manufacturer detects new or higher levels of impurities, they should fully evaluate the impurities and take action to ensure the product is safe for patients.

For additional information well-nigh ARB products, see:

• list of valsartan products nether recall
• list of valsartan products not under think

x/sixteen/2018: UPDATE - FDA releases additional NDMA/NDEA detection method

Update [x/16/2018] FDA is posting a gas chromatography-tandem mass spectrometry (GC-MS/MS) method utilizing liquid injection for detecting the presence of impurities North-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA) in valsartan drug products.

This method provides an additional selection for regulators and manufacture to detect NDMA and NDEA impurities. This method tin can be used alone or in combination with the combined gas chromatography-mass spectrometry (GC/MS) headspace method the agency recently posted. Similar the previously posted methods, this method should exist validated by the user if the resulting information are used to support a required quality assessment of the API or drug product, or if the results are used in a regulatory submission.

10/11/2018: UPDATE - FDA releases method for detection and quantification of both NDMA and NDEA

Update [10/11/2018] ] FDA is posting a redeveloped combined gas chromatography-mass spectrometry (GC/MS) headspace method for detecting the presence of impurities North-Nitrosodimethylamine (NDMA) and Due north-Nitrosodiethylamine (NDEA) in valsartan drug products.

FDA previously posted a GC/MS method for detection of NDMA in valsartan products. Upon detection of NDEA in valsartan products manufactured by Zhejiang Huahai Pharmaceuticals, FDA redeveloped the testing method then that information technology can be used to find and quantify levels of both NDMA and NDEA. This method should exist validated by the user if the resulting information are used to support a required quality assessment of the API or drug product, or if the results are used in a regulatory submission.

FDA is also working on a GC/MS direct injection method for detection of NDMA and NDEA. We will post the method when it is bachelor. This volition provide an additional option for regulators and industry to apply to detect both impurities.

10/v/2018: UPDATE - FDA posts laboratory assay of NDMA levels in recalled valsartan products

Update [x/5/2018] FDA posted laboratory exam results showing NDMA levels in recalled valsartan products. FDA will as well post examination results and an assessment of the cancer risk from NDEA when they are available.

ix/28/2018: UPDATE - FDA places Zhejiang Huahai Pharmaceuticals on import alert

Update [nine/28/2018] FDA placed Zhejiang Huahai Pharmaceuticals on import alert on September 28, 2018, to protect U.South. patients while the active pharmaceutical ingredient (API) manufacturer fully determines how impurities were introduced into its API and remediates its quality systems. The import alarm stops all API fabricated by ZHP and finished drug products made using ZHP's API from legally entering the Us. FDA'due south action follows a recent inspection at ZHP's facility.

FDA reminds manufacturers that information technology is their responsibleness to develop and use suitable methods to discover impurities, including when they make changes to their manufacturing processes. If a manufacturer detects new or higher levels of impurities, they should fully evaluate the impurities and take activity to ensure the product is safe for patients.

viii/22/2018: UPDATE - FDA updates recall lists and releases method for the detection and quantification of NDMA in valsartan

Update [8/22/2018] Torrent Pharmaceuticals Limited is expanding its voluntary recall to all lots of unexpired valsartan-containing drug products due to the detection of NDMA in the active pharmaceutical ingredient (API) manufactured by Zhejiang Huahai Pharmaceuticals.

RemedyRepack, a repackager of Torrent's valsartan/amlodipine/hydrochlorothiazide (HCTZ) tablets, has besides recalled.

FDA has updated the listing of valsartan products under recall and the list of valsartan products non under call up.

Additionally, FDA is releasing a gas chromatography-mass spectrometry (GC/MS) headspace method for manufacturers and regulators to discover and quantify NDMA in valsartan API and finished drug products. The agency is using this method to test potential NDMA-containing APIs and drug products. This method should be validated by the user if the resulting information are used to back up a required quality assessment of the API or drug product, or if the results are used in a regulatory submission.

8/20/2018: UPDATE - FDA updates recalled valsartan-containing production data and presents NDMA levels in some foods

Update [8/20/2018] FDA is alerting wellness intendance professionals and patients that Torrent Pharmaceuticals Limited is voluntarily recalling 14 lots of valsartan/amlodipine/hydrochlorothiazide (HCTZ) tablets. Not all Torrent valsartan products distributed in the U.S. are being recalled.

FDA recently learned Torrent used affected valsartan active pharmaceutical ingredient (API) manufactured by Zhejiang Huahai Pharmaceuticals. FDA testing confirmed NDMA in some Torrent products.

To date, Torrent has non received any reports of adverse events related to this recall.

FDA has updated the list of valsartan products nether remember and the listing of valsartan products non under recollect to incorporate additional repackagers of Slant'due south valsartan products and Torrent's retrieve.

NDMA is a known environmental contaminant. For context, it is plant in water and foods including meats, dairy products and vegetables.

Estimated Range of Daily NDMA Consumption for certain foods (Recommended daily food consumption rates based on Dietary Guidelines for Americans 2015-2020 )

• Cured meat - 0.004-0.23 micrograms¹

• Smoked meat - 0.004-1.02 micrograms ¹

• Grilled meat - 0.006-0.13 micrograms ¹

• Salary - 0.07-0.09 micrograms^two

  • In more ordinary terms, for instance, i pound of bacon may contain 0.304-0.354 micrograms of NDMA

FDA reminds patients taking valsartan from a recalled lot that they should continue taking their electric current medicine until their doctor or pharmacist provides a replacement or a different handling option. Not all valsartan products incorporate NDMA, and then pharmacists may exist able to provide a refill of valsartan medication not affected past the recall, or doctors may prescribe a different medication that treats the aforementioned condition.

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¹ Mavelle, T., B. Bouchikhi, and G. Debry, The occurrence of volatile Northward-nitrosamines in French foodstuffs. Food Chemistry, 1991. 42(3): p. 321-338.

ⁱⁱ  Park, J., et al., Distribution of Seven N-Nitrosamines in Nutrient. Toxicol Res, 2015. 31(3): p. 279-288.

eight/ix/2018: UPDATE - FDA updates recalled valsartan-containing production information

Update [eight/ix/2018] FDA has updated the list of valsartan products nether recall and the list of valsartan products not under recall to incorporate recalls of valsartan-containing products manufactured by Hetero Labs Limited, in India, labeled equally Slant Pharmaceuticals Inc. Not all Camber valsartan products distributed in the U.S. are being recalled.

Camber Pharmaceuticals is recalling certain valsartan tablets considering they contain the impurity Due north-nitrosodimethylamine (NDMA) in the active pharmaceutical ingredient (API). Hetero Labs articles the API for the Camber products using a procedure like to Zhejiang Huahai Pharmaceuticals.

Test results from Hetero Labs show the amount of NDMA establish in its valsartan API exceeds adequate levels; although it is generally lower than the amount discovered in the API manufactured by Zhejiang.

FDA is testing samples of valsartan API and finished products to ostend the extent and amount of NDMA and aid inform the ongoing investigation. The agency has likewise contacted other manufacturers of valsartan API to determine if their manufacturing processes are at take chances for the germination of NDMA, and is working with them to ensure NDMA is not nowadays in future valsartan API.

Valsartan is an angiotensin Ii receptor blocker (ARB), and FDA is investigating whether other types of ARBs are at risk for the presence of NDMA.

Recalled valsartan products labeled as Camber may be repackaged past other companies. FDA volition provide updates as more information becomes available.

eight/two/2018: UPDATE - FDA updates recalled valsartan-containing product information and reminds API manufacturers to evaluate processes for dangerous impurities

Update [8/ii/2018] FDA continues to evaluate valsartan-containing products and has updated the list of products included in the recall and the list of products not included in the recollect. In addition to updating the lists, FDA revised data related to A-S Medication on the listing of products included in the remember. The agency volition continue to provide information when information technology becomes available.

FDA is working with drug manufacturers to ensure future valsartan active pharmaceutical ingredients (APIs) are not at risk of NDMA formation. The bureau reminds manufacturers to thoroughly evaluate their API manufacturing processes, and changes to those processes, to discover any dangerous impurities. If a manufacturer detects new or higher levels of impurity, they should accept action to prevent changes to the product's safe contour.

7/27/2018: UPDATE - FDA updates recalled valsartan-containing production data

Update [vii/27/2018] FDA is updating health care professionals and patients after discovering that several additional companies that repackage drug products are also recalling valsartan-containing products.

FDA has production recall information from iii additional repackagers of valsartan-containing products made past Teva Pharmaceuticals and Prinston Pharmaceuticals Inc. – labeled as A-Southward Medication Solutions LLC, AvKARE and RemedyRepack – and the bureau has added them to the recalled products listing. Two of these companies, A-S Medication and RemedyRepack, may also distribute valsartan products non affected by the call up. The agency is confirming this information and will provide an update one time it is available.

The post-obit additional repackagers are recalling or are expected to recall valsartan-containing products. FDA is working to gather production call back information from these companies and has removed them from the list of products that are not impacted by this recall:

• Bryant Ranch Prepack Inc.
• H. J. Harkins Company Inc. (this company was not originally included on either listing)
• Lake Erie Medical, doing business equally Quality Intendance Products LLC
• NuCare Pharmaceuticals Inc.
• Northwind Pharmaceuticals
• Proficient Rx

It is possible that not all valsartan-containing products repackaged by these companies are impacted by the recollect. FDA continues to evaluate valsartan-containing products and will update the list of products included in the remember and the list of products not included in the recall every bit more information becomes bachelor.

7/27/2018: UPDATE - Analysis of N-nitrosodimethylamine (NDMA) Levels in Recalled Valsartan in the U.S.

Update [7/27/2018] On July 13th, FDA announced a remember of certain batches of valsartan tablets because of an impurity, a chemical known as N-nitrosodimethylamine (NDMA). Valsartan is a medication unremarkably used to treat loftier claret pressure and heart failure.

NDMA has been found to increase the occurrence of cancer in animal studies. These beast studies were done using amounts of NDMA much higher than the impurity levels in recalled valsartan batches. Based on these brute studies, the U.Due south. Environmental Protection Agency considers NDMA a probable human carcinogen—a chemic that tin increment the gamble of cancer in humans. NDMA is found in some h2o supplies and in some foodsⁱ. Consuming up to 96 nanograms NDMA/day is considered reasonably condom for human ingestion². It is estimated that over the course of a person'due south lifetime, consuming this amount of NDMA would result in less than one boosted case of cancer for every 100,000 people. To put this in context, currently one out of every three people in the US volition experience cancer in their lifetime.

The amounts of NDMA found in the recalled batches of valsartan exceeded these adequate levels. The bureau wanted to put some context around the actual potential take a chance posed to patients who used versions of valsartan that may have independent high levels of NDMA. Based on records from the manufacturer of the recalled valsartan, some levels of the impurity may have been in the valsartan-containing products for as long as four years. FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for the full four years, there may be one additional case of cancer over the lifetimes of these 8,000 people. This cess led to FDA'southward decision to have these batches recalled.

Patients taking valsartan from a recalled batch should continue taking their current medicine until their doctor or pharmacist provides a replacement or a different treatment option. It is important to know that not all valsartan products contained NDMA, so pharmacists may be able to provide a refill of valsartan medication from batches that that are not afflicted past the recollect, or doctors may prescribe a different medication that treats the aforementioned indications.

FDA continues to evaluate the safe of valsartan-containing products and volition update the list of products included in the retrieve and the list of products not included in the recall as more than information becomes available. If you are taking a valsartan product, be sure to check to back equally the lists may change.

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^oneFrom Toxnet: https://toxnet.nlm.nih.gov/

Boilerplate Daily Intake: Water: (assume 3 to six ng N-nitrosodimethylamine/l)(i) 6 to 12 ng; directly intake from drinking water is probably much less than 1 ug/day(two). FOOD: (assume <0.ane to="" 84="" ug/kg)(4)=""> <0.16 to="" 134="">
[(ane) Kimoto WI et al; H2o Res 15: 1099-1106 (1981) (2) USEPA; Ambient Water Quality Criteria Doctor: Nitrosamines p.C-14 (1980) EPA 440/five-lxxx-064 (iv) IARC; IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 17: 125-76 (1978)]

²The calculated acceptable intake for NDMA is based on methods described in the ICH Guidance M7(R1) Assessment and Control of Dna Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk
(http://wcms-internet.fda.gov/files/drugs/published/M7-R1-AssessmentAndControlOfDNA-Reactive-Mutagenic-ImpuritiesInPharmaceuticalsToLimitPotentialCarcinogenicRisk-Guidance.pdf)

7/24/2018: UPDATE - FDA publishes a listing of valsartan-containing products not part of the recollect

Update [seven/24/2018] FDA is updating health care professionals and consumers on the agency'southward progress in responding to the ongoing recalls of valsartan, which is used to treat high blood force per unit area and centre failure, due to the presence of NDMA. The agency has posted a list of valsartan-containing products non impacted by this recollect. FDA continues to evaluate valsartan-containing products and volition update the list of products included in the call up and the listing of products not included in the recall every bit more information becomes available.

Manufacturers of these products frequently produce multiple dosage strengths, however not all of them are being recalled. FDA recommends health care professionals and patients carefully bank check these lists. Health care professionals and patients should bank check this statement frequently for any updates.

FDA reminds consumers to go along taking your current medicine until your doctor or pharmacist gives you a replacement or a different treatment choice. Untreated hypertension (high claret pressure) leads to an increment in the risk of heart attacks and stroke. Untreated heart failure increases the risk of hospitalization and death.

Consumers and health intendance professionals should keep to report any adverse reactions with valsartan-containing products, to the FDA's MedWatch program to assistance the agency better understand the scope of the problem:

• Complete and submit the written report online at www.fda.gov/medwatch/report.htm
• Download and consummate the appropriate form, and then submit information technology via fax at 1-800-FDA-0178

7/eighteen/2018: STATEMENT - FDA updates wellness care professionals and patients on recent valsartan recalls

[seven/18/2018] The U.S. Food and Drug Administration is updating health care professionals and consumers following a recent FDA press release nearly voluntary recalls of several drug products containing the active pharmaceutical ingredient (API) valsartan. Valsartan is used to treat loftier blood pressure and heart failure. Not all products containing valsartan are being recalled, and this update will clarify which valsartan-containing products are being recalled.

The recalled products contain an impurity, N-nitrosodimethylamine (NDMA), in the API manufactured by Zhejiang Huahai Pharmaceuticals, Linhai, People's republic of china. The presence of the potentially cancer-causing NDMA was unexpected, and the bureau believes the NDMA is related to changes in the way the active substance was manufactured. Some levels of the impurity may accept been in the valsartan-containing products for every bit long equally four years.

The investigation into valsartan-containing products is ongoing, and the following listing may change. Nosotros will update this argument as we have more information.

There are currently three voluntary recalls related to the NDMA impurity detected in the valsartan API:

• Teva Pharmaceuticals Usa labeled as Major Pharmaceuticals — recall is at the retail level because these products are only used in facilities where they are directly administered to patients by health care professionals: Valsartan 80 mg and 160 mg products;
• Prinston Pharmaceuticals Inc. labeled as Solco Healthcare LLC — call up is at the consumer/user level: Valsartan 40 mg, 80 mg, 160 mg, and 320 mg; and valsartan/HCTZ 80 mg/12.five mg, 160 mg/12.v mg, 160 mg/25 mg, 320 mg/12.v mg, and 320 mg/25 mg products; and
• Teva Pharmaceuticals labeled as Actavis LLC — recall is at the consumer/user level: Valsartan 40 mg, 80 mg, 160 mg, and 320 mg; and valsartan/HCTZ 80 mg/12.five mg, 160 mg/12.5 mg, 160 mg/25 mg, 320 mg/12.v mg, and 320 mg/25 mg products.

Detailed listing of products included in the recollect (PDF - 87 KB)

What should patients know:

• Continue taking your current medicine until your dr. or pharmacist gives you a replacement or a different handling choice.
• Not all valsartan-containing medications are afflicted and being recalled.
• If you are taking any medication containing valsartan, compare the information on your prescription bottle with the information in this list (company, National Drug Code, lot number) to make up one's mind if your current medicine has been recalled. If you are not sure, contact your chemist.
• If you have medicine included in the recall, contact your pharmacist. The chemist may be able to provide you with valsartan made past another visitor. If not, contact your physician immediately to talk over other treatment options.

What wellness care professionals should know:

• FDA has determined the recalled valsartan products pose an unnecessary risk to patients. Therefore, FDA recommends patients use valsartan-containing medicines made by other companies or consider other bachelor treatment options for the patient'due south medical status.
• If you have medication samples from these companies, quarantine the products and do not provide them to patients.

Consumers and health care professionals should written report whatsoever adverse reactions with valsartan-containing products, to the FDA'southward MedWatch program to help the agency better understand the telescopic of the problem:

• Complete and submit the report online at www.fda.gov/medwatch/report.htm
• Download and consummate the appropriate class, then submit it via fax at one-800-FDA-0178

Fda Expands Blood Pressuredrug Recall

Source: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-and-press-announcements-angiotensin-ii-receptor-blocker-arb-recalls-valsartan-losartan

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