The P-I-E-N-O Parkinsn's List Drug Database
cimetidine / TagametTM
ANTI-ULCER:
Hyperacidity
Description: Cimetidine represents the first commercially available drug for peptic ulcer disease that works by antagonizing histamine at the parietal cell. It is classified as an HA-receptor antagonist. Unlike traditional antihistamines used in allergic conditions, cimetidine is used mainly for treating gastrointestinal disorders, although it can be beneficial for other conditions. Cimetidine was approved by the FDA in 1977 and came off patent May 17, 1994. In September 1993, an FDA committee declined permission to market this drug as a nonprescription product but subsequently approved, on March 29, 1995, a lower strength dosage form for OTC use. The OTC formulation will be trade named "Tagamet HB." A nonprescription form of cimetidine was previously available in New Zealand and the UK.
Mechanism of Action: Cimetidine blocks the effects of histamine at the receptor located on the basolateral membrane of the parietal cell (designated as the HA-receptor). The result is a reduction of both gastric volume and gastric acidity. Cimetidine also decreases the amount of gastric acid released in response to other stimuli including food, caffeine, insulin, betazole, or pentagastrin. Because gastric secretions respond to multiple stimuli, cimetidine's effects are not as dramatic as those of omeprazole, which inhibits the final step of acid secretion. Cimetidine does not appear to alter gastric motility, gastric emptying, esophageal pressure, or the secretion rate of the gallbladder or pancreas.
Pharmacokinetics: Cimetidine is rapidly and completely absorbed in the GI tract, but first-pass metabolism reduces oral bioavailability to 60-70%. The rate but not the extent of absorption can be affected by food. The drug distributes throughout body tissues, is found in breast milk, and crosses the placenta. Approximately 48% of an oral dose and 75% of an IV dose of cimetidine is excreted in the urine. The remainder is excreted in the feces or in breast milk. Half-life is roughly 2 hours in patients with normal renal function but increases to 5 hours in anephric patients.
CONTRAINDICATIONS/PRECAUTIONS: Cimetidine should be used cautiously in patients with hepatic disease, such as cirrhosis, or renal disease, such as renal impairment, because clearance can be reduced. Various types of confusional states have been attributed to cimetidine. While decreased clearance would seem to predispose patients to adverse reactions, hepatic disease and/or renal disease have not been shown conclusively to increase the risk for central nervous system reactions.I Nevertheless, lower doses should be used in patients with hepatic and/or renal disease to avoid toxicity.
Cimetidine 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.
Cimetidine is secreted into breast milk. Cimetidine should not be used in women who are breast-feeding.
The safety and efficacy of cimetidine in children is not known. Use should be limited to when the potential benefits outweigh the potential risk.
Many drug interactions have been described when cimetidine was added to a drug regimen. Review Drug Interactions prior to prescribing cimetidine.
DRUG INTERACTIONS: Cimetidine is the classic example of a drug that inhibits cytochrome oxidative hepatic metabolism. Cimetidine can decrease the clearance of other drugs that are metabolized via this pathway. Studies have shown that cimetidine's ability to interfere with this metabolic step is a function of its structure and not of its ability to block HA-receptors since other HA-blockers do not appear to inhibit this metabolic pathway to the same degree as cimetidine. At one time, it was believed that cimetidine interacted with some drugs secondary to its ability to decrease hepatic blood flow. It has since been determined that the predominant mechanism for cimetidine-induced hepatic clearance interactions is secondary to decreased hepatic metabolism. Cimetidine administration can cause serum concentrations of the affected drug to rise, causing toxicity. Drugs affected by cimetidine in this way include: œ-blockers including alprenolol, oxprenolol, and propranolol; carbamazepine; carmustine; fentanyl; flecainide; lidocaine; meperidine; metronidazole; phenytoin; quinidine; theophylline; some tricyclic antidepressants including desipramine, doxepin, imipramine, and nortriptyline; oral contraceptives; and warfarin. Cimetidine also can inhibit the clearance of some benzodiazepines. These include: alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, flurazepam, halazepam, prazepam, and triazolam. Benzodiazepines that do not appear to interact with cimetidine are lorazepam, oxazepam, and temazepam. Cimetidine may also interfere with the clearance of paroxetine, however, additional data is needed to better describe this interaction.
Cimetidine also can reduce the clearance of drugs that are eliminated via renal tubular secretion. Examples include procainamide and theophylline, although the effect of cimetidine on theophylline hepatic elimination is more significant.
Cimetidine can increase nifedipine and nitrendipine area-under-the- curve (AUC), can reduce diltiazem clearance, and has produced variable effects on verapamil clearance. Increased clinical effects of nifedipine were observed during concomitant cimetidine administration. Clinicians should be alert for exaggerated effects of calcium-channel blocker therapy if cimetidine is added to the regimen.
Cimetidine can enhance the myelosuppressive effects of chemotherapeutic drugs or radiation therapy.
Cimetidine can affect the oral absorption of drugs that are susceptible to changes in intragastric pH such as didanosine, ddI and ketoconazole. Rantidine, a drug with actions similar to cimetidine, was shown to increase the oral bioavailability of didanosine, ddI. While the degree of this change was statistically significant, it is unlikely to be clinically significant. Nevertheless, a similar interaction between cimetidine and didanosine, ddI would be expected. Ketoconazole requires an acidic environment for oral absorption. Administration of cimetidine to patients receiving ketoconazole reduces the bioavailability of ketoconazole. Because of the prolonged duration of action of cimetidine, staggering the administration times would not prevent this interaction with ketoconazole. Conversely, cimetidine can enhance oral absorption of ethanol in addition to slowing its clearance.
Antacids can reduce the absorption of cimetidine if given concomitantly; it is recommended that dosages of these drugs be spaced at least an hour apart.
ADVERSE REACTIONS: Adverse reactions during cimetidine therapy occur rarely and are usually mild and transient. However, moderate to severe headaches have been reported in 2.1-3.5% of patients receiving cimetidine; these resolve following discontinuance of the drug. Reversible mental status changes, including agitation, confusion, delirium, hallucinations, hostility, paranoia, depression, and disorientation, have been reported following cimetidine therapy, usually in critically ill patients. A recent 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 agent is more likely to induce CNS reactions than another.I A meta-analysis published in 1989 showed that CNS reactions were no more frequent with cimetidine than with placebo.
Although data exist associating cimetidine with various types of blood cytopenias, the overall incidence of these reactions is low (2.3 per 100,000 patients). Neutropenia and agranulocytosis are the most commonly encountered blood dyscrasias. Cases of leukopenia, thrombocytopenia, and pancytopenia have all been reported during therapy with cimetidine. Although hemolytic anemia has been reported with cimetidine, the casual role of cimetidine remains very controversial. Other factors including underlying diseases or additional drugs could contribute to these hematologic alterations. Recovery is usually rapid after discontinuation of cimetidine.
Gynecomastia and sexual dysfunction including libido decrease and impotence have been seen during cimetidine therapy. These effects may be related to cimetidine's ability to inhibit the metabolism of estradiol.
GI adverse reactions have been reported in patients receiving cimetidine. Diarrhea has been reported during cimetidine therapy but is usually mild and transient. Although rare, pancreatitis, hepatitis, jaundice, and elevated hepatic enzymes have been reported with cimetidine.
Dermatologic reactions are rarely reported and include maculopapular rash, acneiform rash, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis. Hypersensitivity reactions including vasculitis and anaphylaxis have been reported with cimietidine.
PATIENT INFORMATION:
What do cimetidine tablets do?
Cimetidine (TagametTM ) is a type of antihistamine that blocks the release of stomach acid. Cimetidine is used to treat gastric and duodenal ulcers. It can relieve ulcer pain and discomfort, and the heartburn from gastroesophageal reflux disease. Generic cimetidine tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take cimetidine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take cimetidine tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. If you only take cimetidine once a day take it at bedtime. Take your doses at regular intervals. Do not take your medicine more often than directed.
Special precautions for use in children:
This medicine is not for children under 16 years old; give to children only if prescribed by the doctor.
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 cimetidine?
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 cimetidine?
Side effects with cimetidine 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 cimetidine?
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 ulcer to heal.
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.
If you need to take an antacid you should take it at least 1 hour before or 1 hour after cimetidine. Cimetidine will not be as effective if taken at the same time as an antacid.
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 15 and 30C (59 and 86F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.
Parkinsn's Archive Treasures Page
John Cottingham is the webmaster of this site.
