Ranitidine Hydrochloride 71130-06-8

Medical use

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 7 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's main role is in treating gastric and duodenal ulcers and gastroesophageal reflux disease. It is also used to treat pediatric reflux, where it is preferred over a PPI, because it does not induce histologically relevant hyperplastic changes in the parietal cells. Liquid formulations are available for administering to children. Ranitidine can also be co-administered with NSAIDs to reduce the risk of ulceration. 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 IV 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 twenty four hours, usually at night. For ulcer treatment, a 300 mg nighttime 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 4 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

Ranitidine appears to decrease mucosal perfusion in patients with acute renal and 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 vitamin B12 supplementation than those not taking such drugs. Ranitidine and other histamine H2 receptor antagonists may increase the risk of pneumonia in hospitalized patients. They also increase the risk of community-acquired pneumonia in adults and children. Many studies of various types support that use of H2RA drugs such as raniditine increase the risk of infectious diarrhea including traveller's diarrhea and salmonella. H2 antagonists may increase the risk of developing foods allergies. Patients who take these agents develop higher levels of IgE against food, whether they had prior antibodies or not. Even months after discontinuation there was still an elevated level of IgE in 6% of patients in this study.

History and development

Ranitidine was developed by Sir James Black, graduate of the University of St Andrews Bute Medical School, who at the time worked for Glaxo Pharmaceuticals. In an effort to match the success of Smith, Kline & French (prior to the merger of the two companies into GlaxoSmithKline), Glaxo developed cimetidine as the first histamine H₂-receptor antagonist. 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 ten times the activity of cimetidine. Ranitidine has 10% 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 proton pump inhibitors, with omeprazole becoming the biggest-selling drug for many years. 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 heart burn symptoms.