FDA continues to investigate 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 in the table below 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. 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.
The methods FDA used in the laboratory testing are available here.
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.
NDMA ESTIMATED RISK:
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.
|Company||Product||Lots Tested||NDMA level ppm||NDMA level (micrograms-mcg/tablet or oral dose)|
|Sanofi Pharmaceutical||OTC Ranitidine 150mg||19E413M, 19D554, 19A432U, 19C540, 19D431I, 19D442N, 19D423M, 19D464M,||0.07-2.38||0.01-0.36|
|Sanofi Pharmaceutical||OTC Ranitidine 75mg||18L012U, 9A003U, 19B006M, 18M025M, 18N023U, 19B005N, 19A002U, 18N026U||0.10-0.55||0.01-0.04|
|Cardinal Health||OTC Ranitidine 150mg||9FE2953||1.02||0.15|
|Watson||Rx Nizatidine 150mg||1350798M||0.05||0.01|
|Watson||Rx Nizatidine 300mg||1333973A||0.04||0.01|
|Strides Shasun Ltd||Rx Nizatidine 150mg||7704758A||0.11||0.02|
|Strides Shasun Ltd||Rx Nizatidine 300mg||7704022A||0.09||0.03|
|Novitium||Rx Ranitidine 300mg||S18038B||2.85||0.86|
|Dr Reddy’s||Rx Ranitidine 300mg||C805265||0.68||0.20|
|Strides Shasun Ltd||Rx Ranitidine 300mg||7702255A||0.11||0.03|
|Sandoz||Rx Ranitidine 300mg||HU2207||0.82||0.25|
|Strides Shasun Ltd||Rx Ranitidine 300mg||7704537A||0.02||0.00|
|Aurobindo||Rx Ranitidine 300mg||RA3019001-A||1.86||0.56|
|Ajanta Pharma USA Inc||Rx Ranitidine 300mg||PA1229B||0.23||0.07|
|Silarx Pharma||Ranitidine 150mg Syrup||3652081-02661||1.37||0.20|
|Pharma Associates||Ranitidine 150mg Syrup||BE00, BF75, BF77, BF78, BDFF, COAC||0.03-0.07||0.004-0.012|
|Amneal Pharmaceuticals||Ranitidine 300mg||AR181795A, AR190878A, AR190876A, AR191177A, HB05819, HB06119, HL08718||0.52-2.17||0.16-0.65|
|Sanofi Pharmaceutical||Ranitidine 150mg||19D570, 19D428U, 19E408M||0.08-2.17||0.01-0.33|