In September 2019, the probable carcinogen N-nitrosodimethylamine (NDMA) was discovered in ranitidine products from a number of manufacturers, resulting in recalls.

[14][15][16][17] In April 2020, ranitidine was withdrawn from the United States market and suspended in the European Union and Australia due to these concerns.

[27][28][29] It has been withdrawn at regulator request from most markets, including the United States;[12] according to the UK NHS, it has been discontinued globally.

[30] Ranitidine has been discontinued globally, according to the NHS,[30] and is contraindicated due to excess cancer risk and the ready availability of H2 antagonist and PPI alternatives.

[55][56] 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 (NDMA), classified as a probable human carcinogen, at unacceptable levels.

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.

[61] 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.

[68][69][70] The Federal Union of German Associations of Pharmacists (Arzneimittelkommission der Deutschen Apotheker) published a list of recalled products,[71] as did the Therapeutic Goods Administration in Australia.

[72] 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.

[73][74] 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.

In April 2020, new 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.

[19] 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.

[83] In September 2019, Apotex recalled all over-the-counter ranitidine tablets sold in the United States at Walmart, Rite Aid, and Walgreens.

[105] In October 2019, the Department of Health and Social Care of the United Kingdom issued a supply distribution alert (SDA/2019/005) for all oral formulations of ranitidine.

[111][17] In November 2019, Aurobindo Pharma, Amneal Pharmaceuticals, American Health Packaging, Golden State Medical Supply, and Precision Dose recalled some lots of ranitidine tablets, capsules, and syrup.

[124] GlaxoSmithKline, Sanofi, and Teva said they had no plans to reintroduce the drug in the EU, but Accord Healthcare considered the possible reintroduction of ranitidine.

[125] Oral absorption: 50%[125] Protein binding: 15%[126] Metabolism: The major metabolite in the urine is ranitidine N-oxide, which represents less than 4% of the dose.

[1] In general, studies of pediatric patients (aged one month to 16 years) have shown no significant differences in pharmacokinetic parameter values in comparison to healthy adults, when correction is made for body weight.

[1] Ranitidine was first prepared in England as AH19065 by John Bradshaw in the summer of 1977 in the Ware research laboratories of Allen and Hanburys, part of the former Glaxo organisation.

Ranitidine was the result of a rational drug-design process using what was by then a fairly refined model of the histamine H2 receptor and quantitative structure-activity relationships.

Ranitidine was found to have a far-improved tolerability profile (i.e. fewer adverse drug reactions), longer-lasting action, and 10 times the activity of cimetidine.

Ranitidine has 10% of the affinity that cimetidine has to CYP450, so it causes fewer side effects, but other H2 blockers famotidine and nizatidine have no CYP450 significant interactions.

[133][134] In September 2019, the probable carcinogen N-nitrosodimethylamine (NDMA) was discovered in ranitidine products from a number of manufacturers, resulting in recalls; in April 2020, it was withdrawn from the United States market and suspended in Europe and Australia.