The United States Food and Drug Administration (FDA) announces to continue investigating the presence of the N-Nitrosodimethylamine (NDMA) impurity in ranitidine and is now aware of NDMA in nizatidine, which is chemically similar to ranitidine. Both medicines are H2 blockers which decrease the amount of acid in the stomach. FDA has identified NDMA in ranitidine and nizatidine active pharmaceutical ingredient (API) and finished drugs.
FDA is posting its laboratory results showing NDMA levels in all ranitidine and nizatidine samples it tested, including API and finished drug which included tablets and syrup. NDMA was present in all samples tested. Products involved are listed below; details of the NDMA levels are available in the attached FDA website. Testing of ranitidine for injection is still ongoing.
For reference, consuming up to 0.096 micrograms or 0.32 parts per million (ppm) of NDMA per day is considered reasonably safe for human ingestion based on lifetime exposure. FDA has set the acceptable daily intake limit for NDMA at 0.096 micrograms or 0.32 ppm for ranitidine. Although many manufacturers have already recalled ranitidine voluntarily, FDA will recommend recalls to manufacturers with NDMA levels above the acceptable daily intake limit.
FDA also developed a simulated gastric fluid (SGF) model to be used with the LC-MS testing method to estimate the biological significance of in vitro findings. The SGF and simulated intestinal fluid (SIF) models are intended to detect the formation of NDMA in systems that approximate the stomach and intestinal fluids, respectively. The results of these tests showed no additional NDMA generated in the stomach.
FDA has determined that the levels of NDMA in ranitidine and nizatidine are similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats.
Details of the Companies and Tested Products:
- Sanofi Pharmaceutical (OTC Ranitidine 150mg; lot tested: 19E413M, 19D554, 19A432U, 19C540, 19D431I, 19D442N, 19D423M, 19D464M)
- Sanofi Pharmaceutical (OTC Ranitidine 75mg; lot tested: 18L012U, 9A003U, 19B006M, 18M025M, 18N023U, 19B005N, 19A002U, 18N026U)
- Cardinal Health (OTC Ranitidine 150mg; lot tested: 9FE2953)
- Watson (Rx Nizatidine 150mg; lot tested: 1350798M)
- Watson (Rx Nizatidine 300mg; lot tested: 1333973A)
- Strides Shasun Ltd (Rx Nizatidine 150mg; lot tested: 7704758A)
- Strides Shasun Ltd (Rx Nizatidine 300mg; lot tested: 7704022A)
- Novitium (Rx Ranitidine 300mg; lot tested: S18038B)
- Dr Reddy's (Rx Ranitidine 300mg; lot tested: C805265)
- Strides Shasun Ltd (Rx Ranitidine 300mg; lot tested: 7702255A)
- Sandoz (Rx Ranitidine 300mg; lot tested: HU2207)
- Strides Shasun Ltd (Rx Ranitidine 300mg; lot tested: 7704537A)
- Aurobindo (Rx Ranitidine 300mg; lot tested: RA3019001-A)
- Ajanta Pharma USA Inc (Rx Ranitidine 300mg; lot tested: PA1229B)
- Silarx Pharma (Ranitidine 150mg Syrup; lot tested: 3652081-02661)
- Pharma Associates (Ranitidine 150mg Syrup; lot tested: BE00, BF75, BF77, BF78, BDFF, COAC)
- Amneal Pharmaceuticals (Ranitidine 300mg; lot tested: AR181795A, AR190878A, AR190876A, AR191177A, HB05819, HB06119, HL08718)
- Sanofi Pharmaceutical (Ranitidine 150mg; lot tested: 19D570, 19D428U, 19E408M)
Please refer to the following website in FDA for details:
http://www.fda.gov/drugs/drug-safety-and-availability/laboratory-tests-ranitidine
In Hong Kong, the above products are not registered pharmaceutical products
Currently, there are 67 registered pharmaceutical products containing ranitidine in Hong Kong. These products in the forms of oral preparations and injections are controlled as over-the-counter medicines and prescription-only medicines respectively; and there is no registered pharmaceutical products containing nizatidine. So far, the Department of Health (DH) has not received any case of adverse drug reaction related to ranitidine or nizatidine.
Related news on the detection of N-nitrosodimethylamine (NDMA) in ranitidine products was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 16 Sep 2019, with the latest update posted on 31 Oct 2019. Letters to inform local healthcare professionals were issued by the DH on 18 Sep 2019. The DH has contacted the relevant overseas drug regulatory authorities for further information regarding the detection of NDMA in ranitidine products, and continues to remain vigilant on the update findings and investigation result announced by the authorities for consideration of any action deemed necessary.
The DH has contacted the certificate holders of all registered ranitidine products for follow up on the local impact of the issue; and to provide evidence that NDMA in the products are below the acceptable limit, and samples of ranitidine-containing products have been collected from the market for analysis. When any health risks are posed to the public, a press statement will be issued as soon as possible. The following are the main content of the press statements issued previously:
- On 24 Sep 2019, the DH endorsed a licensed drug wholesaler, GlaxoSmithKline Ltd, to recall all Zantac products (HK-42792, HK-42793, HK-30459, HK-42045) from the Hong Kong market as a precautionary measure due to the presence of NDMA in the products.
- On 25 Sep 2019, the DH endorsed licensed drug wholesalers Hind Wing Co Ltd and Top Harvest Pharmaceuticals Co Ltd to recall Apo-Ranitidine Tablets (HK-42273, HK-41873) and Zantidon Tablets 150mg (HK-64329) respectively.
- On 27 Sep 2019, the DH endorsed licensed drug manufacturer APT Pharma Limited and licensed drug wholesaler Eugenpharm International Limited to recall Amratidine Tablets 150mg (HK-53143) and Peptil H 150 Tablets 150mg (HK-65103) respectively.
- On 30 Sep 2019, the DH endorsed licensed drug wholesaler Vast Resources Pharmaceutical Limited to recall Weidos Tablets 150mg (HK-62210).
- On 11 Oct 2019, the DH endorsed licensed drug wholesaler Hind Wing Co Ltd to recall Epadoren Solution for Injection 50mg/2ml (HK-61752).
- On 1 Nov 2019, the DH endorsed licensed drug wholesaler Welldone Pharmaceuticals Limited to recall six ranitidine-containing products: Epirant Tab 150mg (HK-56826), Welldone Ranitidine Tab 150mg (HK-57473), Kin Pak Tab 150mg (HK-56824), Wah Tat Tab 150mg (HK-56823), Super Pro Tab 150mg (HK-56825) and Glo-Tac Tab 150mg (HK-57472).
Patients who are taking ranitidine-containing products should not stop taking the medicines, but should seek advice from their healthcare professionals for proper arrangement, e.g. use of alternative medicines with similar uses.
Ends/Saturday, Nov 02, 2019
Issued at HKT 13:00
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