Ranitidine
Encyclopedia
Ranitidine 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.
(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. Proton pump inhibitors are more effective for the prevention of NSAID-induced ulcers.
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.
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 that use of H2 receptor antagonists such as raniditine may increase the risk of infectious diarrhea, including traveller's diarrhea and salmonella.
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 there was still an elevated level of IgE in 6% of patients in this study.
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 (QSAR).
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 reaction
s), 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 inhibitor
s, 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 heartburn symptoms.
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
H2-receptor antagonist
H2-receptor antagonist
The H2 receptor antagonists are a class of drugs used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells. H2 antagonists are used in the treatment of dyspepsia, although they have been surpassed in popularity by the more effective ...
that inhibits stomach acid
Gastric acid
Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1 to 2 and is composed of hydrochloric acid , and large quantities of potassium chloride and sodium chloride...
production. It is commonly used in treatment of peptic ulcer
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
disease (PUD) and gastroesophageal reflux disease (GERD). Ranitidine is also used alongside fexofenadine
Fexofenadine
Fexofenadine is an antihistamine drug used in the treatment of hayfever and similar allergy symptoms...
and other antihistamines for the treatment of skin conditions such as hives. Ranitidine is also known to give false positives for methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
on drug tests.
Medical use
Certain preparations of ranitidine are not available over the counterOver-the-counter drug
Over-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
(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
Bismuth
Bismuth is a chemical element with symbol Bi and atomic number 83. Bismuth, a trivalent poor metal, chemically resembles arsenic and antimony. Elemental bismuth may occur naturally uncombined, although its sulfide and oxide form important commercial ores. The free element is 86% as dense as lead...
(which acts as a mild antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
) as a citrate
Citrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...
salt (ranitidine bismuth citrate, Tritec), to treat Helicobacter pylori
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
infections. This combination is usually given with clarithromycin
Clarithromycin
Clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia , skin and skin structure infections...
, 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. Proton pump inhibitors are more effective for the prevention of NSAID-induced ulcers.
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
Zollinger-Ellison syndrome
Zollinger–Ellison syndrome is a triad of gastric acid hypersecretion, severe peptic ulceration, and non-beta cell islet tumor of pancreas . In this syndrome increased levels of the hormone gastrin are produced, causing the stomach to produce excess hydrochloric acid. Often the cause is a tumor of...
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 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 vitamin 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.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 that use of H2 receptor antagonists such as raniditine may increase the risk of infectious diarrhea, including traveller's diarrhea and salmonella.
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 there was still an elevated level of IgE in 6% of patients in this study.
History and development
Ranitidine was first prepared as AH19065 by John Bradshaw in the summer of 1976 in the Ware research laboratories of Allen & HanburysAllen & Hanburys
Allen and Hanburys Ltd was a British pharmaceutical manufacturer, absorbed by Glaxo Laboratories in 1958.-History:The business was founded in 1715 in Old Plough Court, Lombard Street, London, by Silvanus Bevan, a Welshman, apothecary and a Quaker...
Ltd, part of the Glaxo organization ,. Its development was a response to the first in class histamine H2-receptor antagonist, cimetidine
Cimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
, 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
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
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 (QSAR).
Glaxo refined the model further by replacing the imidazole
Imidazole
Imidazole is an organic compound with the formula C3H4N2. This aromatic heterocyclic is a diazole and is classified as an alkaloid. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents...
-ring of cimetidine with a furan
Furan
Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen. The class of compounds containing such rings are also referred to as furans....
-ring with a nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
-containing substituent, and in doing so developed ranitidine. Ranitidine was found to have a far-improved tolerability profile (i.e. fewer adverse drug reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s), 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
Famotidine
Famotidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and it is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease . It is commonly marketed by Johnson & Johnson/Merck under the trade names Pepcidine and Pepcid and by...
and nizatidine
Nizatidine
Nizatidine is a histamine H2-receptor antagonist that inhibits stomach acid production, and commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease...
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 inhibitor
Proton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
s, with omeprazole
Omeprazole
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...
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 heartburn symptoms.
External links
- Reflux Remedies: ranitidine (Zantac)
- Consumer information on Zantac from the manufacturer
- Zantac official website GlaxoSmithKlineGlaxoSmithKlineGlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
- Zantac OTC official website Boehringer Ingelheim