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.

 

CompanyProductLots TestedNDMA level ppmNDMA level (micrograms-mcg/tablet or oral dose)
Sanofi PharmaceuticalOTC Ranitidine 150mg19E413M, 19D554, 19A432U, 19C540, 19D431I, 19D442N, 19D423M, 19D464M,0.07-2.380.01-0.36
Sanofi PharmaceuticalOTC Ranitidine 75mg18L012U, 9A003U, 19B006M, 18M025M, 18N023U, 19B005N, 19A002U, 18N026U0.10-0.550.01-0.04
Cardinal HealthOTC Ranitidine 150mg9FE29531.020.15
WatsonRx Nizatidine 150mg1350798M0.050.01
WatsonRx Nizatidine 300mg1333973A0.040.01
Strides Shasun LtdRx Nizatidine 150mg7704758A0.110.02
Strides Shasun LtdRx Nizatidine 300mg7704022A0.090.03
NovitiumRx Ranitidine 300mgS18038B2.850.86
Dr Reddy’sRx Ranitidine 300mgC8052650.680.20
Strides Shasun LtdRx Ranitidine 300mg7702255A0.110.03
SandozRx Ranitidine 300mgHU22070.820.25
Strides Shasun LtdRx Ranitidine 300mg7704537A0.020.00
AurobindoRx Ranitidine 300mgRA3019001-A1.860.56
Ajanta Pharma USA IncRx Ranitidine 300mgPA1229B0.230.07
Silarx PharmaRanitidine 150mg Syrup3652081-026611.370.20
Pharma AssociatesRanitidine 150mg SyrupBE00, BF75, BF77, BF78, BDFF, COAC0.03-0.070.004-0.012
Amneal PharmaceuticalsRanitidine 300mgAR181795A, AR190878A, AR190876A, AR191177A, HB05819, HB06119, HL087180.52-2.170.16-0.65
Sanofi PharmaceuticalRanitidine 150mg19D570, 19D428U, 19E408M0.08-2.170.01-0.33

 

Source: FDA