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Ranitidine Structural Formulae.png
Systematic (IUPAC) name
Clinical data
Trade names Zantac
AHFS/Drugs.com monograph
MedlinePlus a601106
Licence data US FDA:link
Pregnancy cat. B1 (AU) B (US)
Legal status Pharmacy Only (S2) (AU) OTC (US) P/POM (UK)
Routes Oral, IV
Pharmacokinetic data
Bioavailability 39 to 88%
Protein binding 15%
Metabolism Hepatic
Half-life 2–3 hours
Excretion 30–70% Renal
CAS number 66357-35-5 YesY
ATC code A02BA02
A02BA07 (ranitidine bismuth citrate)
PubChem CID 657345
IUPHAR ligand 1234
DrugBank DB00863
ChemSpider 571454 YesY
UNII 884KT10YB7 YesY
KEGG D00422 YesY
Chemical data
Formula C13H22N4O3S 
Mol. mass 314.4 g/mol
 N (what is this?)  (verify)

Ranitidine (/rəˈnɪtɨdn/; 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.[1]

Medical use[edit]

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 also be coadministered with NSAIDs to reduce the risk of ulceration. Proton-pump inhibitors (PPIs) are more effective for the prevention of NSAID-induced ulcers.[2]

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.

Adverse effects[edit]

Ranitidine appears to decrease mucosal perfusion in patients with acute renal or cardiac failure, and increases their risk of death.[3] All drugs in its class decrease gastric intrinsic factor secretion, which can significantly reduce absorption of protein-bound vitamin B12 in humans.[4] Elderly patients taking H2 receptor antagonists are more likely to require B12 supplementation than those not taking such drugs.[5] H2 blockers may also reduce the absorption of drugs (azole antifungals, calcium carbonate) that require an acidic stomach.[6] 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.[7]

Ranitidine and other histamine H2 receptor antagonists may increase the risk of pneumonia in hospitalized patients.[8] They may also increase the risk of community-acquired pneumonia in adults and children.[9] 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.[10][11][12][13][14]

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.[15] 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.[16]

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.[17]

History and development[edit]

Zantac (ranitidine) 300 mg tablets

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.[18][19] 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.[20]

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.[citation needed] 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.[21]

See also[edit]

  • Famotidine, aka Pepcid AC, Pepcidine: another popular H2-receptor antagonist


  1. ^ Poklis, A; Hall KV, Still J, Binder SR (March 1991). "Ranitidine interference with the monoclonal EMIT d.a.u. amphetamine/methamphetamine immunoassay". Journal of analytical toxicology 15 (2): 101–103. doi:10.1093/jat/15.2.101. PMID 2051743. 
  2. ^ "Reflux Remedies: ranitidine". PharmaSight OTC Health. PharmaSight.org. Retrieved 16 November 2011. 
  3. ^ Jakob SM, Parviainen I, Ruokonen E, et al. (2005). "Lack of effect of ranitidine on gastric luminal pH and mucosal PCO2 during the first day in the ICU". Acta Anaesthesiol Scand 49 (3): 390–396. doi:10.1111/j.1399-6576.2005.00651.x. 
  4. ^ Salom IL, Silvis SE, Doscherholmen A. (1982). "Effect of cimetidine on the absorption of vitamin B12". Scand J Gastroenterol 17 (1): 129–131. doi:10.3109/00365528209181056. PMID 7134827. 
  5. ^ Mitchell SL, Rockwood K. (2001). "The association between antiulcer medication and initiation of cobalamin replacement in older persons". J Clin Epidemiol 54 (5): 531–534. doi:10.1016/S0895-4356(00)00340-1. 
  6. ^ "Reflux Remedies: ranitidine". PharmaSight OTC Health. PharmaSight.org. Retrieved 16 November 2011. 
  7. ^ Pali-Schöll I, Jensen-Jarolim E (April 2011). "Anti-acid medication as a risk factor for food allergy". Allergy 66 (4): 469–77. doi:10.1111/j.1398-9995.2010.02511.x. PMID 21121928. 
  8. ^ Mallow S, Rebuck JA, Osler T, et al. (2004). "Do proton pump inhibitors increase the incidence of nosocomial pneumonia and related infectious complications when compared with histamine-2 receptor antagonists in critically ill trauma patients?". Curr Surg 61 (5): 452–458. doi:10.1016/j.cursur.2004.03.014. PMID 15475094. 
  9. ^ Canani, RB; Cirillo, P; Roggero, P; Romano, C; Malamisura, B; Terrin, G; Passariello, A; Manguso, F; Morelli, L; Guarino, A; Working Group on Intestinal Infections of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition, (SIGENP) (May 2006). "Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children.". Pediatrics 117 (5): e817–20. doi:10.1542/peds.2005-1655. PMID 16651285. 
  10. ^ Cobelens FGJ, Leentvarr-Kuijpers A, Kleijnen J, Coutinho RA. (1998). "Incidence and risk factors of diarrhoea in Dutch travellers: Consequences for priorities in pre-travel health advice". Trop Med Intern Health 3: 896–903. 
  11. ^ Neal KR, Briji SO, Slack RCB, et al. (1994). "Recent treatment with H2-antagonists and antibiotics and gastric surgery as risk factors for Salmonella infection". Br Med J 308 (6922): 176. doi:10.1136/bmj.308.6922.176. PMID 7906170. 
  12. ^ Neal KR, Scott HM, Slack RC, Logan RF. (1996). "Omeprazole as a risk factor for Campylobacter gastroenteritis: Case-control study". BMJ 312 (7028): 414–415. doi:10.1136/bmj.312.7028.414. PMID 8601113. 
  13. ^ Wickramasinghe LSP, Basu SK. (1984). "Salmonellosis during treatment with ranitidine". Br Med J 289 (6454): 1272. doi:10.1136/bmj.289.6454.1272. 
  14. ^ Ruddell WS, Axon AT, Findlay JM, et al. (1980). "Effect of cimetidine on gastric bacterial flora". Lancet i: 672–674. 
  15. ^ Untersmayr E, Bakos N, Scholl I, et al. (2005). "Anti-ulcer drugs promote IgE formation toward dietary antigens in adult patients". FASEB J 19 (6): 656–658. doi:10.1096/fj.04-3170fje. PMID 15671152. 
  16. ^ "Review: Fungal sepsis in Zantac". eHealthMe. Retrieved 19 October 2013. 
  17. ^ Amit V Bangia, Narendra Kamath, and Vidushi Mohan (2011). "Ranitidine-induced thrombocytopenia: A rare drug reaction". Indian J Pharmacol 43 (1): 76–7. doi:10.4103/0253-7613.75676. PMC 3062128. PMID 21455428. 
  18. ^ Lednicer, Daniel (Editor). "Chronicles of Drug Discovery". ACS Professional Reference Books, Volume 3, pages 45-81 1993. ISBN 0-8412-2733-0.
  19. ^ US patent US4128658, "Aminoalkyl furan derivatives", 1978
  20. ^ Laurence Brunton, John Lazo, Keith Parker (August 2005). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11 ed.). McGraw-Hill. p. 972. doi:10.1036/0071422803. ISBN 0-07-142280-3. 
  21. ^ Pelot, Daniel, (M.D.). "Digestive System : New Drug for Heartburn". The New Book of Knowledge : Medicine & Health, Grolier : Danbury, Connecticut. 1990. p.262. ISBN 0-7172-8244-9. Library of Congress 82-645223

External links[edit]