|Systematic (IUPAC) name|
|Licence data||US FDA:|
|Pregnancy cat.||B1 (AU) B (US)|
|Legal status||Pharmacy Only (S2) (AU) OTC (US) P/POM (UK)|
|Bioavailability||39 to 88%|
A02BA (ranitidine bismuth citrate)
|Mol. mass||314.4 g/mol|
|(what is this?)|
Ranitidine (//; trade name Zantac) is a histamine H2-receptor antagonist that inhibits stomach acid production. It is commonly used in treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD). Ranitidine is also used alongside fexofenadine and other antihistamines for the treatment of skin conditions such as hives. Ranitidine is also known to give false positives for methamphetamine on drug tests.
Certain preparations of ranitidine are available over the counter (OTC) in various countries. In the United States, 75-mg and 150-mg tablets are available OTC. Zantac OTC is manufactured by Boehringer Ingelheim. In Australia, packs containing seven or 14 doses of the 150-mg tablet are available in supermarkets, small packs of 150-mg and 300-mg tablets are schedule 2 pharmacy medicines. Larger doses and pack sizes still require a prescription.
Outside the United States and Canada, ranitidine is combined with bismuth (which acts as a mild antibiotic) as a citrate salt (ranitidine bismuth citrate, Tritec), to treat Helicobacter pylori infections. This combination is usually given with clarithromycin, an antibiotic.
Ranitidine can be administered preoperatively to reduce the risk of aspiration pneumonia. The drug not only increases gastric pH, but also reduces the total output of gastric juice. Ranitidine may have an antiemetic effect when administered preoperatively.
It can be administered intravenously in intensive care units to critically ill patients (particularly geriatric ones) to reduce the risk of gastric bleeding.
The usual dose of ranitidine is either 150 mg twice a day or 300 mg once every 24 hours, usually at night. For ulcer treatment, a 300-mg night-time dose is especially important - as the increase in gastric/duodenal pH promotes healing overnight when the stomach and duodenum are empty. Conversely, for treating reflux, smaller and more frequent doses are more effective.
Ranitidine used to be administered long term for reflux treatment, sometimes indefinitely. However, PPIs have taken over this role.
In some patients with severe reflux, up to 600 mg of ranitidine can be administered daily, usually in four lots of 150 mg. Such a high dose was not unusual in the past, but nowadays a once-a-day PPI is used instead - both for convenience and because they are more effective in raising gastric pH. Patients with Zollinger-Ellison syndrome have been given doses of 6000 mg per day without any harm.
Ranitidine appears to decrease mucosal perfusion in patients with acute renal or cardiac failure, and increases their risk of death. All drugs in its class decrease gastric intrinsic factor secretion, which can significantly reduce absorption of protein-bound vitamin B12 in humans. 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 (azole antifungals, calcium carbonate) that require an acidic stomach. By suppressing acid-mediated breakdown of proteins, antacid preparations such as ranitidine may lead to an elevated risk of developing food or drug allergies, due to undigested proteins then passing into the gastrointestinal tract, where sensitisation occurs. Whether this risk occurs with only long-term use or with short-term use, as well, is unclear.
Ranitidine and other histamine H2 receptor antagonists may increase the risk of pneumonia in hospitalized patients. They may also increase the risk of community-acquired pneumonia in adults and children. Multiple studies suggest the use of H2 receptor antagonists such as raniditine may increase the risk of infectious diarrhoea, including traveller's diarrhoea and salmonellosis.
H2 antagonists may increase the risk of developing food allergies. Patients who take these agents develop higher levels of IgE 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 this study.
Fungal sepsis has been observed in some patients on ranitidine.
Additionally, thrombocytopenia 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 sensitized individual. Typically, the platelet count falls to 80% of normal, and thrombocytopenia may be associated with neutropenia and anemia.
History and development
Ranitidine was first prepared as AH19065 by John Bradshaw in the summer of[when?] in the Ware research laboratories of Allen & Hanburys Ltd, part of the Glaxo organization. Its development was a response to the first in class histamine H2-receptor antagonist, cimetidine, developed by Sir James Black at Smith, Kline and French, and launched in the United Kingdom as Tagamet in November 1976. Both companies would eventually become merged as GlaxoSmithKline following a sequence of mergers and acquisitions starting with the integration of Allen & Hanbury's Ltd and Glaxo to form Glaxo Group Research in 1979, and ultimately with the merger of Glaxo Wellcome and SmithKline Beecham in 2000. 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.
Glaxo refined the model further by replacing the imidazole ring of cimetidine with a furan ring with a nitrogen-containing substituent, and in doing so developed ranitidine. 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.
Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug by 1988. It has since largely been superseded by the even more effective PPIs, with omeprazole becoming the biggest-selling drug for many years. Some patients[which?] prefer ranitidine rather than omeprazole because these patients reported fewer side effects with ranitidine, and ranitidine was effective enough for their needs. When omeprazole and ranitidine were compared in a study of 144 people with severe inflammation and erosions or ulcers of the esophagus, 85% of those treated with omeprazole healed within eight weeks, compared to 50% of those given ranitidine. In addition, the omeprazole group reported earlier relief of heartburn symptoms.
- Famotidine, aka Pepcid AC, Pepcidine: another popular H2-receptor antagonist
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- "Reflux Remedies: ranitidine". PharmaSight OTC Health. PharmaSight.org. Retrieved 16 November 2011.
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- "Review: Fungal sepsis in Zantac". eHealthMe. Retrieved 19 October 2013.
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- US patent US4128658, "Aminoalkyl furan derivatives", 1978
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- Reflux Remedies: ranitidine (Zantac)
- Consumer information on Zantac from the manufacturer
- Zantac official website GlaxoSmithKline
- Zantac OTC official website Boehringer Ingelheim