Ranitidine Market Status
Ranitidine is not available for clinical use in the United States and many other countries following its market withdrawal in April 2020 due to contamination with N-nitrosodimethylamine (NDMA), a probable human carcinogen. 1
Regulatory Action and Rationale
- The US Food and Drug Administration requested all manufacturers to immediately withdraw ranitidine from the market on April 1,2020, due to unacceptable levels of NDMA contamination 1
- NDMA is classified as a probable human carcinogen, raising significant safety concerns about chronic ranitidine exposure 2, 1
- The contamination issue was first identified in 2019 through a citizen petition to the FDA 3
Evidence Regarding NDMA Formation
The evidence on whether ranitidine converts to NDMA in the human body remains controversial:
- One 2016 study demonstrated that ranitidine intake increased urinary NDMA excretion 400-fold (from 110 to 47,600 ng over 24 hours), with NDMA excretion rates equaling or exceeding those seen in schistosomiasis patients, where N-nitrosamines are implicated in bladder cancer 2
- However, a more recent 2021 randomized, double-blind, placebo-controlled trial found no statistically significant difference in 24-hour urinary NDMA excretion between ranitidine (300 mg) and placebo in 18 healthy participants, whether consuming cured-meats or noncured-meats diets 3
- The 2021 trial concluded that findings "do not support that ranitidine is converted to NDMA in a general, healthy population" 3
Clinical Implications
- Alternative H2-receptor antagonists remain available, including famotidine, cimetidine, and nizatidine 4, 5
- Famotidine is dosed at 20 mg twice daily (equivalent to ranitidine 150 mg twice daily) 4
- Proton pump inhibitors remain the preferred option for most acid suppression indications 6
- For patients previously on ranitidine, switching to famotidine or a proton pump inhibitor is appropriate depending on the clinical indication 6, 5
Historical Clinical Context
Prior to withdrawal, ranitidine was widely used and generally well-tolerated, with adverse effects occurring in less than 2% of patients 7. Multiple guidelines from 2005-2020 recommended its use for various indications including anaphylaxis management 4, perioperative aspiration prophylaxis 4, short bowel syndrome 4, and gastroesophageal reflux disease 6, 5. However, these recommendations are now obsolete given the drug's unavailability.