Ranitidine


Ranitidine, sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It is used in the treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellison syndrome. It can be given by mouth, injection into a muscle, or injection into a vein.
In September 2019, the probable carcinogen N-nitrosodimethylamine was discovered in ranitidine products from a number of manufacturers, resulting in recalls. In April 2020, ranitidine was withdrawn from the United States market and suspended in the European Union and Australia due to these concerns. A reformulated ranitidine was approved in Australia in October 2024, and in the United States in November 2025.
Common side effects include headaches, and pain or burning sensation if given by injection. Serious side effects may include cancer, liver problems, a slow heart rate, pneumonia, and the potential of masking stomach cancer. It is also linked to an increased risk of Clostridioides difficile colitis. Ranitidine is an H2 histamine receptor antagonist that works by blocking histamine, thus decreasing the amount of acid released by cells of the stomach.
Ranitidine was discovered in England in 1976 and came into commercial use in 1981. It is on the World Health Organization's List of Essential Medicines.

Medical uses

  • Relief of heartburn
  • Short-term and maintenance therapy of gastric and duodenal ulcers
  • With nonsteroidal anti-inflammatory drugs to reduce the risk of ulceration Proton-pump inhibitors are more effective for the prevention of NSAID-induced ulcers.
  • Pathologic gastrointestinal hypersecretory conditions such as Zollinger–Ellison syndrome
  • Gastroesophageal reflux disease
  • Erosive esophagitis
  • Part of a multidrug regimen for Helicobacter pylori eradication to minimise the risk of duodenal ulcer recurrence
  • Recurrent postoperative ulcer
  • Upper GI bleeding
  • For prevention of acid-aspiration pneumonitis during surgery, it can be administered preoperatively. The drug increases gastric pH, but generally has no effect on gastric volume. In a 2009 meta-analysis comparing the net benefit of PPIs and ranitidine to reduce the risk of aspiration before anaesthesia, ranitidine was found to be more effective than PPIs in reducing the volume of gastric secretions. Ranitidine may have an anti-emetic effect when administered preoperatively.
  • Prevention of stress-induced ulcers in critically ill patients
  • Used together with diphenhydramine as secondary treatment for anaphylaxis; after first-line epinephrine.

    Adverse effects

These adverse effects for ranitidine have been reported as events in clinical trials:

Central nervous system

Rare reports have been made of ranitidine causing malaise, dizziness, somnolence, insomnia, and vertigo. In severely ill, elderly patients, cases of reversible mental confusion, agitation, depression, and hallucinations have been reported.

Cardiovascular

Arrhythmias such as tachycardia, bradycardia, atrioventricular block, and premature ventricular beats have also been reported.

Gastrointestinal

Drugs in the H2 receptor blocker class of medicines have the potential to cause vitamin B12 deficiency, secondary to a reduction in food-bound vitamin B12 absorption. Elderly patients taking H2 receptor antagonists are more likely to require B12 supplementation than those not taking such drugs. H2 blockers may also reduce the absorption of drugs that require an acidic stomach. In addition, multiple studies suggest the use of H2 receptor antagonists such as ranitidine may increase the risk of infectious diarrhoea, including traveller's diarrhoea and salmonellosis. A 2005 study found that by suppressing acid-mediated breakdown of proteins, ranitidine may lead to an elevated risk of developing food or drug allergies, due to undigested proteins then passing into the GI tract, where sensitisation occurs. Patients who take these agents develop higher levels of immunoglobulin E against food, whether they had prior antibodies or not. Even months after discontinuation, an elevated level of IgE in 6% of patients was still found in the study.

Liver

, liver failure, hepatitis, and jaundice have been noted, and require immediate discontinuation of the drug. Blood tests can reveal an increase in liver enzymes or eosinophilia, although in rare instances, severe cases of hepatotoxicity may require a liver biopsy.

Lungs

Ranitidine and other histamine H2 receptor antagonists may increase the risk of pneumonia in hospitalised patients. Ranitidine increases the risk of community-acquired pneumonia in adults and children.

Blood

is a rare but known side effect. Drug-induced thrombocytopenia usually takes weeks or months to appear, but may appear within 12 hours of drug intake in a sensitised individual. Typically, the platelet count falls to 80% of normal, and thrombocytopenia may be associated with neutropenia and anemia.

Skin

Rash, including rare cases of erythema multiforme, and rare cases of hair loss and vasculitis have been seen.

Precautions

Disease-related concerns

Relief of symptoms due to the use of ranitidine does not exclude the presence of a gastric malignancy. In addition, with kidney or liver impairment, ranitidine must be used with caution. It should be avoided in patients with porphyria, as it may precipitate an attack.

Children

In children, the use of gastric acid inhibitors has been associated with an increased risk for development of acute gastroenteritis and community-acquired pneumonia. A cohort analysis including over 11,000 neonates reported an association of H2 blocker use, and an increased incidence of necrotizing enterocolitis in very-low-birth-weight neonates. In addition, about a six-fold increase in mortality, necrotizing enterocolitis, and infection such as sepsis, pneumonia, urinary tract infection was reported in patients receiving ranitidine in a cohort analysis of 274 VLBW neonates.

Drug tests

Ranitidine may return a false positive result with some commercial urine drug screening kits for testing for drugs of abuse.

Cancer-causing due to inherent instability

In June 2019, Valisure informed the US Food and Drug Administration that Zantac-branded and generic ranitidine resulted in very high levels of NDMA in the human body "due to an inherent instability of the ranitidine molecule".
In September 2019, the FDA acknowledged that ranitidine medicines, including some products sold under the brand name Zantac, contained a nitrosamine impurity called N-nitrosodimethylamine, classified as a probable human carcinogen, at unacceptable levels. Health Canada announced that it was assessing NDMA in ranitidine and requested that manufacturers stop the distribution of ranitidine products in Canada until the NDMA levels in the products are found to be safe. Health Canada announced that ranitidine drugs were being recalled by Sandoz Canada, Apotex Inc., Pro Doc Limitée, Sanis Health Inc., and Sivem Pharmaceuticals ULC. The European Medicines Agency started a European Union-wide review of ranitidine medicines at the request of the European Commission.
In October 2019, the US FDA observed that the third-party laboratory that found very high levels of NDMA was using higher temperatures in its tests to detect nitrosamine impurities. The NDMA was mostly generated by the added heat, but the higher temperatures are recommended for using a gas chromatography–mass spectrometry method to test for NDMA in valsartan and angiotensin II receptor blockers. The FDA stated that it recommends using a Liquid Chromatography-High Resolution Mass Spectrometry testing protocol to test samples of ranitidine. Its LC-HRMS testing method does not use elevated temperatures, and has shown the presence of much lower levels of NDMA in ranitidine medicines than were reported by the third-party laboratory. International regulators using similar LC-MS testing methods have also shown the presence of lower but still unacceptable levels of NDMA in ranitidine samples. The FDA provided additional guidance about using another LC-MS method based on a triple-quadrupole MS platform.
In September 2019, Sandoz issued a "precautionary distribution stop" of all medicines containing ranitidine, followed a few days later by a recall of ranitidine hydrochloride capsules in the United States. The Italian Medicines Agency recalled all ranitidine that uses an active pharmaceutical ingredient from Saraca Laboratories. The Federal Union of German Associations of Pharmacists published a list of recalled products, as did the Therapeutic Goods Administration in Australia.
In November 2019, the FDA stated that its tests found levels of NDMA in ranitidine and nizatidine that are similar to those that one may typically ingest with common foods such as grilled or smoked meats. The FDA also stated that its simulated gastric fluid model tests and simulated intestinal fluid model tests indicated that NDMA is not formed when exposed to acid in the stomach with a normal diet. The FDA advised companies to recall their ranitidine if testing shows levels of NDMA above the acceptable daily intake. At the same time, it indicated that some levels of NDMA found in medicines still exceeded the agency's acceptable levels.
In December 2019, the FDA asked manufacturers of ranitidine and nizatidine products to expand their NDMA testing to include all lots of the medication before making them available to consumers.
By the end of 2019, ranitidine had already fallen from the 40th most commonly prescribed medication in the United States in 2018, to 53rd place for 2019, with about 13.6million prescriptions for the year, versus nearly 19 million the previous year. This reflects total prescriptions for all of 2019, while safety concerns affected sales in only the final 4 months of the year.
In April 2020, FDA testing and evaluation prompted by information from third-party laboratories confirmed that NDMA levels increase in ranitidine even under normal storage conditions, and NDMA has been found to increase significantly in samples stored at higher temperatures, including those at which the product may be exposed during distribution and handling by consumers. The testing also showed that the level of NDMA increases as ranitidine medication ages. These conditions may raise the NDMA level above the acceptable daily intake limit. The EMA completed and issued their EU-wide review at the end of the month and the European Commission suspended all ranitidine products in the EU.
In August 2020, the EMA provided guidance to marketing authorization holders for avoiding the presence of nitrosamine impurities and asked them to review all chemical and biological human medicines for the presence of nitrosamines and to test the products at risk. In September 2020, the FDA issued guidance about the control of nitrosamine impurities in human drugs. An implementation plan was issued in February 2021.
In 2022, cancer concerns were found in a Taiwanese nationwide population study.
The FDA issued revised guidelines about nitrosamine impurities in September 2024.