The P-I-E-N-O Parkinsn's List Drug Database
ranitidine / ZantacTM
ANTIULCER:
Description: Ranitidine is a histamine receptor antagonist similar to cimetidine and famotidine. Actions of and indications for ranitidine differ little from the other agents, except that ranitidine is 5-12 times as potent as cimetidine at the histamine receptor and has less affinity than cimetidine for the cytochrome hepatic enzyme system. As a result, ranitidine is much less likely than cimetidine to interact with other drugs. Similar to other HA-receptor antagonists, the main use of ranitidine is in the treatment of gastrointestinal disorders. Ranitidine was approved by the FDA in June 1983 and goes off patent December 1995. In December 1994, the manufacturer filed an NDA for ranitidine in combination with bismuth citrate and in October 1994 filed an NDA for a non-prescription form of ranitidine. An FDA advisory committee recommended approval for the OTC form (75 mg) on July 13, 1995.
Mechanism of Action: Ranitidine competitively inhibits the binding of histamine receptors on gastric parietal cells (designated as the HA receptor), thus reducing basal and nocturnal gastric acid secretion. The drug also decreases the amount of gastric acid released in response to stimuli such as food, caffeine, insulin, betazole, or pentagastrin. Ranitidine reduces the total volume of gastric juice, thereby indirectly decreasing pepsin secretion. The drug does not appear to alter gastric motility, gastric emptying, esophageal pressures, biliary secretions, or pancreatic secretions. Ranitidine is not an antimuscarinic anticholinergic. Ranitidine may aid in gastromucosal healing, and it may protect the mucosa from the irritant effects caused by aspirin and nonsteroidal antiinflammatory agents.
Pharmacokinetics: The oral bioavailability of ranitidine is about 50-60% due to first-pass elimination. The presence of food in the GI tract does not appear to affect the extent or rate of absorption. The drug distributes throughout the body fluids and tissues, and can be found in breast milk and CSF. Using inhibition of pentagastrin-induced acid secretion as an indicator, ranitidine's effects persist for 8-12 hours. Ranitidine undergoes metabolism in the liver, and both the unchanged drug and its metabolites are excreted in the urine and feces. The half-life of the drug is 2-3 hours but increases to roughly 5 hours in anuric patients. Tubular secretion as well as glomerular filtration account for ranitidine renal elimination.
CONTRAINDICATIONS/PRECAUTIONS: Ranitidine should be used cautiously in patients with hepatic disease or renal disease, specifically renal impairment, because accumulation can occur. Ranitidine dosage should be reduced in patients with creatinine clearances of less than 50 ml/min.
Ranitidine is classified as pregnancy category B. Animal studies have not demonstrated a risk to the fetus but there are no adequate studies in pregnant women. Risks-benefits should be considered during pregnancy and in women expecting to become pregnant.
Ranitidine is excreted into breast milk. Risks-benefits should be considered in women who are breast-feeding.
DRUG INTERACTIONS: The extent of enzyme inhibition by ranitidine is significantly less than that of cimetidine; the clearance of drugs metabolized by the hepatic microsomal mixed-function oxidase system usually is not affected by concomitant administration of ranitidine at doses of 300 mg/day or less. At least one report exists, however, of theophylline toxicity occurring during ranitidine therapy. If large doses of ranitidine are administered (such as in the treatment of Zollinger-Ellison syndrome), cimetidine-like drug interactions are possible with ranitidine.
Propantheline bromide increases the bioavailability of ranitidine by 23% when the drugs are administered concomitantly. Propantheline bromide is believed to delay gastric emptying, increase transit time, and thereby increase the peak plasma concentration of ranitidine.
Ketoconazole requires an acidic environment for oral absorption. Therapy with ranitidine can reduce the bioavailability of ketoconazole. Because the effects on intragastric pH are sustained, separating the time of administration of these two drugs will not alleviate the problem. It may be necessary to substitute fluconazole in place of ketoconazole.
Didanosine, ddI, is an acid-labile compound. Administration of ranitidine prior to didanosine was found to increase didanosine serum concentrations, although the magnitude was slight. While the degree of this change was statistically significant, it is unlikely to be clinically significant.
Cimetidine can increase nifedipine area-under-the-curve. Although to a smaller degree, ranitidine has been shown to have the same effect. Clinicians should be alert for exaggerated nifedipine effects if ranitidine is added to the regimen.
Antacids can slightly decrease ranitidine absorption. Administer these agents at least an hour apart.
Oral cefuroxime axetil area-under-the-curve was reduced by more than 40% when ranitidine was coadministered. Although the clinical significance of this interaction is unclear, one should be aware of possible antibiotic failure if ranitidine is prescribed with oral cefuroxime axetil.
Although some in vitro studies have suggested HA-receptor antagonists inhibit gastric alcohol dehydrogenase, a small study of patients receiving treatment for duodenal ulcer with either famotidine or ranitidine did not demonstrate altered ethanol pharmacokinetics.
ADVERSE REACTIONS: Similar to other HA antagonists, adverse reactions during ranitidine therapy are infrequent. Adverse reactions during ranitidine therapy occur rarely and are usually mild and transient.
GI adverse reactions have been reported in patients receiving ranitidine. These reactions include diarrhea or constipation, nausea/vomiting and abdominal pain. Although rare, hepatitis, jaundice, and elevated hepatic enzymes have been reported with ranitidine. Pancreatitis, a rare but serious reaction, has also been reported.
Although data exist associating ranitidine with various types of blood cytopenias, the overall incidence of these reactions is low. Neutropenia and agranulocytosis are the most commonly encountered blood dyscrasias. Cases of leukopenia, thrombocytopenia, and pancytopenia have all been reported. Other factors including underlying diseases or additional drugs may have contributed to these hematologic alterations. Recovery is usually rapid after discontinuation of ranitidine.
Reversible mental status changes, including agitation, delirium, hallucinations, hostility, paranoia, depression, and disorientation, have been reported following ranitidine therapy. Other CNS adverse reactions include insomnia, headache, vertigo, and dizziness. A review of central nervous system reactions to HA-blockers revealed that the incidence rate varies widely depending on the specific report, and that no single HAantagonist is more likely to induce CNS reactions than another.I
Gynecomastia and sexual dysfunction including libido decrease and impotence have been seen during ranitidine therapy.
Dermatologic reactions are rarely reported and include maculopapular rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, and alopecia. Hypersensitivity reactions including anaphylaxis have been reported with ranitidine.
PATIENT INFORMATION:
What do ranitidine tablets or capsules do?
Ranitidine (ZantacTM ) is a type of antihistamine that blocks the release of stomach acid. Ranitidine is used to treat gastric and duodenal ulcers. It can relieve ulcer pain and discomfort, and the heartburn from gastroesophageal reflux disease. Generic ranitidine tablets or capsules are not yet available.
What should my doctor, dentist, or pharmacist know before I take ranitidine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take ranitidine tablets or capsules by mouth. Follow the directions on the prescription label. Swallow the tablets or capsules with a drink of water. If you only take ranitidine once a day take it at bedtime. Take your medicine at regular intervals. Do not take your medicine more often than directed.
Special precautions for use in children:
This medicine is not for use in children under 12 years old.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.
What other medicines can interact with ranitidine?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking ranitidine?
Side effects with ranitidine are infrequent but include:
Let your doctor know if you get any of these side effects.
What do I need to watch for while I take ranitidine?
Tell your doctor if your ulcer pain does not improve or gets worse. You may need to take this medicine for several days as prescribed before your symptoms improve. Finish the full course of tablets prescribed by your doctor even if you feel better.
Do not self-medicate with aspirin, ibuprofen or other antiinflammatory medicines; these can aggravate your ulcer and may make it bleed.
Do not smoke cigarettes or drink alcohol; these increase irritation in your stomach and can lengthen the time it will take for your ulcers to heal.
If you need to take an antacid you should take it at least 1 hour before or 1 hour after ranitidine. Ranitidine will not be as effective if taken at the same time as an antacid.
If you get black, tarry stools or vomit up what looks like coffee grounds, call your doctor at once. You may have a bleeding ulcer.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 2 and 25C (36 and 77F). Protect from light and moisture. Keep container tightly closed. Throw away any unused medicine after the expiration date.
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