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Additional information about the drug Ranitidine


Ranitidine, sold under the trade name Zantac among others, is a medication which decreases stomach acid production.
Common side effects include headaches and pain or burning if given by injection.
Ranitidine was discovered in 1976 and came into commercial use in 1981.
Contents
1 Medical uses
1.1 Preparations
1.2 Dosing
2 Contraindication
3 Adverse effects
3.1 Central nervous system
3.2 Cardiovascular
3.3 Gastrointestinal
3.4 Liver
3.5 Lungs
3.6 Blood
3.7 Skin
4 Warnings and precautions
4.1 Disease-related concerns
4.2 Pregnancy
4.3 Lactation
4.4 Children
4.5 Drug tests
5 Pharmacology
5.1 Mechanism of action
5.2 Pharmacokinetics
5.2.1 Elderly
5.2.2 Children
6 History
7 See also
8 References
9 External links
Medical uses
Relief of heartburn
Short-term and maintenance therapy of gastric and duodenal ulcers
Ranitidine can also be given with NSAIDs to reduce the risk of ulceration. Proton-pump inhibitors (PPIs) are more effective for the prevention of NSAID-induced ulcers.
Pathologic gastrointestinal (GI) hypersecretory conditions such as Zollinger–Ellison syndrome
Gastroesophageal reflux disease (GERD)
Erosive esophagitis
Part of a multidrug regimen for Helicobacter pylori eradication to reduce the risk of duodenal ulcer recurrence
Recurrent postoperative ulcer
Upper GI bleeding
Prevention of acid-aspiration pneumonitis during surgery: ranitidine can be administered preoperatively to reduce the risk of aspiration pneumonia. The drug increases gastric pH, but generally has no effect on gastric volume. In a 2009 meta-analysis comparing the net benefit of proton pump inhibitors and ranitidine to reduce the risk of aspiration before anesthesia, ranitidine was found to be more effective than proton pump inhibitors in reducing the volume of gastric secretions. Ranitidine may have an antiemetic effect when administered preoperatively.
Prevention of stress-induced ulcers in critically ill patients
Used together with diphenhydramine as secondary treatment for anaphylaxis ; after first-line epinephrine.
Preparations
Certain preparations of ranitidine are available over the counter (OTC) in various countries. In the United States, 75- and 150-mg tablets are available OTC. Zantac OTC is manufactured by Sanofi Consumer Healthcare. (Previously manufactured by Boehringer Ingleheim) In Australia and the UK, 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.
Dosing
For ulcer treatment, a 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 addition, a fairly rapid tachyphylaxis can develop within six weeks of initiation of treatment, further limiting its potential for long-term use.
People with Zollinger–Ellison syndrome have been given very high doses without any harm.
Contraindication
Ranitidine is contraindicated for patients known to have hypersensitivity to the drug.
Adverse effects
The following adverse effects have been reported as events in clinical trials:
Central nervous system
Rare reports have been made of malaise, dizziness, somnolence, insomnia, and vertigo. In severely ill, elderly patients, cases of reversible mental confusion, agitation, depression, and hallucinations have been reported.
Cardiovascular
Arrhythmias such as tachycardia, bradycardia, atrioventricular block, and premature ventricular beats have also been reported.
Gastrointestinal
All drugs in its class have the potential to cause vitamin B 12 deficiency secondary to a reduction in food-bound vitamin B 12 absorption. Even months after discontinuation, an elevated level of IgE in six percent of patients was still found in this study.
Liver
Cholestatic hepatitis, liver failure, hepatitis, and jaundice have been noted, and require immediate discontinuation of the drug.
Lungs
Ranitidine and other histamine H 2 receptor antagonists may increase the risk of pneumonia in hospitalized patients.
Blood
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.
Skin
Rash, including rare cases of erythema multiforme and rare cases of hair loss and vasculitis have been seen.
Warnings and precautions
Disease-related concerns
With gastric malignancies, relief of symptoms due to the use of ranitidine does not exclude the presence of a gastric malignancy. In addition, with kidney or liver impairment, ranitidine must be used with caution. Finally, ranitidine should be avoided in patients with porphyria, as it may precipitate an attack.
Pregnancy
This drug is rated pregnancy category B in the United States.
Lactation
Ranitidine enters breast milk, with peak concentrations seen at 5.5 hours after the dose in breast milk. Caution should be exercised when prescribed to nursing women.
Children
In children, the use of gastric acid inhibitors has been associated with an increased risk for development of acute gastroenteritis and community-acquired pneumonia.
Drug tests
Ranitidine may return a false positive on some commercial drug testing kits.
Pharmacology
Mechanism of action
Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine H 2 receptors found in gastric parietal cells. This results in decreased gastric acid secretion and gastric volume, and reduced hydrogen ion concentration.
Pharmacokinetics
Absorption: Oral: 50%
Protein binding: 15%
Metabolism: N -oxide is the principal metabolite.
Half-life elimination: With normal renal function, ranitidine taken orally has a half-life of 2.5–3.0 hours. If taken intravenously, the half-life is generally 2.0–2.5 hours in a patient with normal creatinine clearance.
Excretion: The primary route of excretion is the urine. In addition, about 30% of the orally administered dose is collected in the urine as non-absorbed drug in 24 hours.
Elderly
In the elderly population, the plasma half-life of ranitidine is prolonged to 3–4 hours secondary to decreased kidney function causing decreased clearance.
Children
In general, studies of pediatric patients (aged 1 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.
History
Zantac (ranitidine) 300-mg tablets
Ranitidine was first prepared as AH19065 by John Bradshaw in the summer of 1977 in the Ware research laboratories of Allen & Hanburys, part of the Glaxo organization. Its development was a response to the first in class histamine H 2 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 H 2 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 H 2 blockers famotidine and nizatidine have no CYP450 significant interactions.
Ranitidine was introduced in 1981 and was the world’s biggest-selling prescription drug by 1987. 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 heartburn symptoms.
See also
Famotidine (trade names Pepcid, Pepcidine) — another popular H 2 receptor antagonist
Nizatidine

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