Cimetidine
Cimetidine is a generic medication for the drug :
Cimetidine medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Cimetidine 200 mg
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Cimetidine 400 mg
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Cimetidine 600 mg
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Cimetidine 800 mg
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Drug Interactions
Drug-Food Interactions
Take cimetidine with meals and at bedtime. See Action and Clinical Pharmacology, Pharmacokinetics, Absorption.
Drug-Laboratory Interactions
Patients should be off cimetidine for at least one week prior to the urea breath test for H. pylori, to prevent false negative results.
Cimetidine may increase levels of the following tests: alanine aminotransferase, serum alkaline phosphatase, serum amylase, serum aspartate aminotransaminase, serum bilirubin, blood urea nitrogen, serum C3 complement, serum creatinine, plasma follicle stimulating hormone, serum gamma-glutamyltransferase, serum high-density lipoprotein cholesterol, serum lactate dehydrogenase, serum lipase, serum prolactin, serum testosterone, serum uric acid.
Cimetidine may decrease levels of the following tests: blood erythrocytes, plasma insulin, plasma parathyroid hormone assay, blood platelet, urine porphobilinogen, serum testosterone, serum triiodothyronine (T3).
Cimetidine
Drug-Drug Interactions
| Interacting Drug | Effect | Clinical Comment |
|---|---|---|
| Antacids | Simultaneous administration of antacids with cimetidine reduces cimetidine serum levels possibly by adsorbing to the cimetidine in the gastrointestinal tract. Data is conflicting regarding this interaction depending on single dose versus multiple dose studies. | Clinical significance unknown. If cimetidine is taken with food, take antacids 1 hour after, to avoid this potential interaction. Space antacids 1 hour before or after cimetidine administration if cimetidine is taken on an empty stomach. |
| Amiodarone | Cimetidine may increase amiodarone serum levels by inhibiting hepatic metabolism of amiodarone or uptake of amiodarone by hepatocytes. | Monitor amiodarone levels when cimetidine is initiated, discontinued or if there is a change in the dose. Consider using an alternate H2-receptor antagonist. |
| Atazanavir | Cimetidine may decrease atazanavir levels by reducing its absorption. | Avoid combination. Separating the doses may not prevent this interaction. |
| Azole Antifungals, i.e., itraconazole, ketoconazole, posaconazole | By suppressing gastric acid, cimetidine may decrease absorption of azole antifungals, decreasing bioavailability and resulting in a loss of antifungal efficacy. | Avoid combination. Consider using a non-interacting antifungal such as fluconazole, voriconazole or terbinafine, if an H2-receptor antagonist is needed. Consider giving glutamic acid hydrochloride 680 mg, 15 minutes before administration of ketoconazole, on an empty stomach, to enhance its absorption. |
| Benzodiazepines, i.e., alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, flurazepam, midazolam, triazolam | Increased serum levels of benzodiazepines undergoing oxidative metabolism in the liver or their active metabolites. | Upon initiation of cimetidine, observe for signs and symptoms of increased plasma levels of benzodiazepines such as prolonged sedation. Warn patients of possible impairment of judgment and reflexes. Consider switching to lorazepam, oxazepam or temazepam as they undergo glucuronide conjugation or consider using an alternate H2-receptor antagonist. |
| Beta Blockers, i.e., carvedilol, labetalol, metoprolol, propranolol, timolol | Increased plasma levels of beta blockers that undergo significant hepatic metabolism. | Use beta blockers that are not hepatically metabolized, such as atenolol or nadolol, or use an alternate H2-receptor antagonist such as ranitidine or famotidine. |
| Carbamazepine | Cimetidine may transiently increase plasma levels of carbamazepine by inhibiting its metabolism. Decreased carbamazepine clearance has been shown when steady states have not been reached. Transient decrease in carbamazepine clearances were observed in trials where cimetidine was withheld until steady state carbamazepine concentrations were attained. | Upon initiation of cimetidine, observe for signs and symptoms of carbamazepine toxicity such as somnolence, dizziness, nystagmus and twitching, especially during the first few weeks of therapy. Monitor for carbamazepine levels when cimetidine is discontinued or if there is a change in dose. Consider using an alternate H2-receptor antagonist such as ranitidine. |
| Carmustine | Cimetidine may increase bone marrow suppression of carmustine by an unknown mechanism. | Monitor for excessive bone marrow suppression, such as leukopenia, thrombocytopenia, neutropenia, with concomitant use of cimetidine and carmustine. An alternate H2-receptor antagonist such as ranitidine may be theoretically less likely to interact. |
| Clozapine | Cimetidine may increase serum clozapine levels by decreasing its hepatic metabolism. | Avoid combination. Monitor for signs and symptoms of clozapine toxicity such as diaphoresis, dizziness, vomiting, generalized weakness and lightheadedness on standing, if cimetidine is initiated and decreased therapeutic effects when cimetidine is discontinued. Consider using an alternate H2-receptor antagonist such as ranitidine. |
| Cyclosporine | Concomitant use may increase serum creatinine levels as it may compete with creatinine for renal tubular secretion; blood cyclosporine levels seem not affected by cimetidine. | Monitor serum creatinine levels if used concomitantly. Consider using an alternate H2-receptor antagonist such as ranitidine. |
| Diltiazem | Cimetidine may increase serum levels of diltiazem by inhibiting hepatic metabolism of diltiazem. | Monitor patients for bradycardia or hypotension when initiating, discontinuing or changing the dose of cimetidine. Adjust diltiazem dose, if needed. Consider using an alternate H2-receptor antagonist. |
| Dofetilidea | Cimetidine may increase plasma dofetilide levels by reducing renal and hepatic metabolism of dofetilide. | Avoid combination because it may result in QTc interval prolongation with cimetidine co-administration. Consider using an alternate H2-receptor antagonist such as ranitidine at doses ≤150 mg twice daily if necessary. May consider proton pump inhibitors and antacids. |
| Erlotinib | By suppressing gastric acid, cimetidine may decrease absorption resulting in decreased serum levels of erlotinib. | Avoid combination. Separating the doses may not prevent this interaction. |
| Ethanol | Cimetidine may increase ethanol peak levels by increasing its absorption and decreasing its metabolism. | Avoid combination. Combination can lead to increased risk of intoxication and worsening of symptoms related to peptic ulcer or gastroesophageal reflux disease. |
| Lidocaine | Cimetidine may increase lidocaine serum levels by inhibiting its metabolism, decrease its protein binding and/or decrease its volume of distribution. | Clinical significance unknown. If used concomitantly, monitor for adverse effects of lidocaine toxicity such as lightheadedness and paresthesias. Measure lidocaine plasma levels. Adjust lidocaine dose, if needed. Consider using an alternate H2-receptor antagonist such as ranitidine, famotidine or nizatidine. |
| Metformin | Cimetidine may increase metformin serum levels by inhibiting its tubular secretion resulting in reduced renal clearance. | Consider using an alternate H2-receptor antagonist such as famotidine. Monitor for signs and symptoms of lactic acidosis such as hyperventilation, tachycardia or nausea, if used concomitantly, especially in patients with reduced renal function. Adjust metformin dose, if needed. |
| Mirtazapine | Remeron RD product monograph lists cimetidine as an agent that increases the AUC of mirtazapine by about 60%. | Consider monitoring for somnolence and arrhythmia with concomitant use. Adjust mirtazapine dose when initiating, discontinuing or changing the dose of cimetidine. |
| Nifedipine | Cimetidine may increase nifedipine serum levels by inhibiting its metabolism and/or increasing its bioavailability due to increased pH. | Monitor patients for altered effects of nifedipine when initiating, discontinuing or changing the dose of cimetidine. Adjust nifedipine dose if needed. |
| Phenytoin | Cimetidine may increase serum phenytoin levels by inhibiting its hepatic metabolism. | Avoid combination. Monitor for signs and symptoms of phenytoin toxicity such as nystagmus, ataxia or confusion with concomitant use. Monitor phenytoin levels upon initiation, discontinuation or change in dose of cimetidine. |
| Procainamide | Cimetidine may increase procainamide and its metabolite, N-acetylprocainamide serum levels by decreasing its clearance. | Avoid combination. Monitor serum procainamide and NAPA levels. Adjust procainamide dose, if needed. |
| Quinidine | Cimetidine may increase serum quinidine levels by inhibiting its hepatic metabolism and/or decreasing its renal clearance and/or increased absorption. | Avoid combination. Monitor for signs and symptoms of quinidine toxicity such as ECG abnormalities with concomitant use. Monitor quinidine serum levels upon initiation, discontinuation or change in dose of cimetidine. Consider using an alternate H2-receptor antagonist such as ranitidine, famotidine and nizatidine. |
| Selective Serotonin Reuptake Inhibitors (SSRIs), i.e., citalopram, escitalopram, paroxetine | Cimetidine may increase serum levels of SSRIs by inhibiting CYP2C19. | Monitor for altered SSRI effect when cimetidine is initiated, discontinued or changed in dose. Adjust SSRI dose as needed. Consider using an alternate H2-receptor antagonist such as ranitidine. |
| Sirolimus | The Rapamune product monograph lists cimetidine as an agent that may increase sirolimus blood levels. | Monitor blood sirolimus trough levels when cimetidine is initiated, discontinued or if there is a change in the dose. |
| Tacrolimus | Advagraf and Prograf product monographs lists cimetidine as an agent that may increase tacrolimus blood levels. | Monitor for signs and symptoms of tacrolimus toxicity such as hypomagnesemia, mild elevations of renal function makers such as creatinine, hyperreflexia, oliguria, tremor and elevations in liver enzymes with concomitant use. |
| Theophyllines, e.g., aminophylline, theophylline | Cimetidine may increase serum theophylline levels by inhibiting its hepatic metabolism. | Monitor for signs and symptoms of theophylline toxicity such as seizures, arrhythmias, metabolic abnormalities (e.g., hypokalemia, hypomagnesemia, hypophosphatemia) with concomitant use. Monitor theophylline levels upon initiation, discontinuation or change in dose of cimetidine. If cimetidine is initiated, a decrease in the theophylline dose may be necessary. Consider using an alternate H2-receptor antagonist such as ranitidine, famotidine and nizatidine. |
| Tricyclic Antidepressants, i.e., amitriptyline, desipramine, doxepin, imipramine, nortriptyline | Cimetidine may increase serum levels of tricyclic antidepressants by inhibiting its hepatic metabolism and/or increasing its bioavailability. | Consider using an alternate H2-receptor antagonist such as ranitidine, famotidine and nizatidine. Adjust dose of the tricyclic antidepressant as necessary, if used concomitantly. Monitor for anticholinergic symptoms such as severe dry mouth, urinary retention, dizziness and blurred vision with concomitant use. |
| Warfarin | Cimetidine may inhibit hepatic metabolism of warfarin therefore increasing its effects. | Avoid combination. If used concomitantly, monitor INR and signs and symptoms of bleeding when cimetidine is initiated, discontinued or if there is a change in the dose. Adjust warfarin dose as necessary. Consider using an alternate H2-receptor antagonist such as ranitidine, famotidine and nizatidine. |
Overview
Cimetidine inhibits cytochrome P450 enzymes specifically CYP1A2, 2C9, 2D6 and 3A4. Drugs that are metabolized by these isoenzymes may be affected when used concurrently with cimetidine. By altering the gastric pH, cimetidine may affect the absorption of certain drugs such as ketoconazole or itraconazole.
Dosage and Administration
Cimetidine
Dose in Adult Patients with Renal Impairment
| Creatinine Clearance | Dose Adjustment |
|---|---|
| >50 mL/min | No adjustment |
| 10–50 mL/min | Decrease dose by 50% |
| <10 mL/min | Decrease dose by 75% |
Recommended Dose and Dosage Adjustment
Administration
Usually taken with food and at bedtime.
Hepatic Impairment
Reduce cimetidine dose in severe liver disease. Cimetidine may cause confusion in patients with hepatic insufficiency possibly because of high plasma concentrations.
Cimetidine
Dose in Adult Patients
| Indication | Dose | Duration of Therapy | Clinical Comment |
|---|---|---|---|
| Duodenal ulcer, active | 800 mg po once daily or 600 mg po BID or 300 mg po QID | 4 weeks minimum | |
| Duodenal ulcer, prevention of recurrence | 400 mg po daily or 300 mg po BID | At least 6 to 12 months | |
| Gastric ulcer, active | 800 mg po once daily or 400 mg po BID or 600 mg po BID or 300 mg po QID | 6 to 8 weeks minimum | |
| Gastric ulcer, prevention of recurrence | 400 mg po once daily or 300 mg po BID | At least 6 to 12 months | |
| Gastroesophageal reflux disease (GERD) | 800 mg po once daily or 600 mg po BID or 300 mg po QID | 8 to 12 weeks | |
| NSAID-induced lesions, treatment | 800 mg po once daily or 400 mg po BID | If duodenal ulcer: 4 weeks minimum If gastric ulcer: 6 to 8 weeks | Discontinue NSAID, if possible. Test and treat if positive for H. pylori. Double dose of H2RAs effectively reduce the risk of NSAID-induced gastric and duodenal endoscopic ulcers. Standard doses are not effective. |
| NSAID-induced lesions, prevention of recurrence | 400 mg po once daily | At least 6 to 12 months if NSAID is discontinued | If ongoing NSAID treatment required, recurrence of lesions may be prevented by continuous concomitant treatment with cimetidine. However, PPIs are more effective than H2RAs. |
| Pathologic hypersecretory conditions (e.g., Zollinger-Ellison syndrome) | 300 mg po QID. Maximum 2400 mg po daily | Indefinite | PPIs may be more effective in suppressing acid secretion in patients with Zollinger-Ellison syndrome. Cimetidine 400 mg po BID has been used in systemic mastocystosis. |
| Helicobacter pylori eradication | Cimetidine 400 mg po BID Bismuth subsalicylate 525 mg po QID (available as 262 mg tablets) Metronidazole 250 mg po QID Tetracycline 500 mg po QID | 10 to 14 days | Quadruple therapy requires complex dosing frequency and high pill count. Predictors of treatment failure include poor compliance and antibiotic resistance. Consider in patients with penicillin hypersensitivity or in those previously treated with macrolides. PPIs are considered first line. H2RA can be substituted in the quadruple therapy, if patient cannot tolerate PPIs. |
| Non-ulcer dyspepsia (NUD) | 400 mg po BID | Relative to placebo and antacids, cimetidine showed benefit in relieving pain and nausea, but not bloating, when given for 6 weeks. Patients with NUD may benefit from cimetidine therapy as it may relieve epigastric discomfort. |
Dosage in Dialysis
In patients with renal insufficiency, cimetidine may cause mental confusion possibly because of high plasma concentrations. Patients undergoing hemodialysis may experience gastric hypersecretion. Cimetidine should be given after hemodialysis because 5 to 20% is dialyzable. Peritoneal dialysis does not remove cimetidine and no adjustment is necessary.
Cimetidine
Dose in Pediatric Patients
| Age | Dose | Maximum dose | Clinical Comment |
|---|---|---|---|
| 0 to 4 weeks | 5 to 10 mg/kg/day in divided doses every 8 to 12 hours | The maximum dose in pediatric patients should not exceed the maximum adult dose for the same clinical use Cimetidine). | Data is limited. |
| 1 month to 1 year | 10 to 20 mg/kg/day in divided doses every 6 to 12 hours | ||
| 1 year to 12 years | 20 to 40 mg/kg/day in divided doses every 6 hours |
Adverse Reactions
Renal
elevated creatinine, urinary retention, acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody where the patient was reactive with myeloperoxidase.
Hepatic/Biliary/Pancreatic
increased AST/ALT, pancreatitis.
Gastrointestinal
collagenous colitis.
Hematologic
agranulocytosis, granulocytopenia (several cases), neutropenia, thrombocytopenia, pancytopenia (several cases), aplastic anemia, hemolytic anemia.
Cimetidine
More Common Adverse Drug Reactions (≥1%)
| Body System | Effect |
|---|---|
| Central Nervous System | headache |
| Endocrine | gynecomastia |
| Gastrointestinal | nausea, vomiting |
Immune
delayed hypersensitivity.
Less Common Adverse Drug Reactions (<1%)
Miscellaneous
arthralgia, myalgia, edema of the breast, fever.
Central Nervous System
agitation, disorientation, dizziness, hallucination, mental confusion, somnolence, delirium and depression (several cases).
Ophthalmologic
optic neuropathy.
Dermatologic
erythema multiforme (1 case), Stevens-Johnson syndrome (1 case), toxic epidermal necrolysis (1 case), exfoliative dermatitis, generalized exfoliative erythroderma, baboon-like syndrome, reversible alopecia.
Sexual Function/Reproduction
impotence, galactorrhea. Climacteric symptoms specifically hot flushes. Profuse sweating, anxiety and dizziness in young man on maintenance hemodialysis.
Cardiovascular
arrhythmia, bradycardia, hypotension, tachycardia, heart block.
Indications and Clinical Use
Geriatrics
Monitor for drug interactions if cimetidine is initiated as this population may be on multiple medications. May increase risk of neurologic adverse effects (see Warnings and Precautions).
Pediatrics
Since data in children younger than 16 years old are limited, the manufacturers do not recommend the use of cimetidine unless the benefits outweigh the risks. Limited clinical experience with pediatric cimetidine dosing is available (see Dosage and Administration).
Overdosage
For management of a suspected drug overdose, CPhA recommends that you contact your regional Poison Control Centre. See the eCPS Directories section for a list of Poison Control Centres.
Warnings and Precautions
Geriatrics
Decreased cimetidine clearance may increase the possibility of CNS adverse effects in the elderly.
Renal
Since cimetidine is excreted by the kidneys, dose adjustment is needed in patients with renal failure. Increase in serum creatinine early in cimetidine therapy is frequent and possibly due to competitive renal tubular secretion. This does not signify deteriorating renal function. Interstitial nephritis has also been reported, which subsides with withdrawal of cimetidine.
Special Populations
Gastrointestinal
Cimetidine may mask symptoms of gastric malignancy.
Peri-Operative Considerations
H2RAs may be administered 2 hours preoperatively to decrease gastric acidity.
Neurologic
Confusion, agitation, psychosis, paranoia, depression, anxiety, hallucinations, hostility, delirium and disorientation may occur, especially in the elderly (≥50 years) and in those with hepatic or renal insufficiency. The condition is more likely at higher doses and develops 2 to 3 days after starting cimetidine. It is reversible and resolves within 3 to 4 days of stopping cimetidine.
Pediatrics (≤16 years)
Since data in children younger than 16 years old are limited, the manufacturers do not recommend the use of cimetidine unless the benefits outweigh the risks. Limited clinical experience with pediatric cimetidine dosing is available where 20 to 40 mg/kg daily has been used (see Dosage and Administration).
Respiratory
Cimetidine and other agents which decrease gastric acid may increase the risk of community-acquired pneumonia.
Pregnant Women
Pregnancy Category BM. Cimetidine crosses the placental barrier. To date, there have been no reports of increased congenital malformations ascribed to cimetidine in humans. No evidence of impaired fertility or harm to the fetus was observed in reproduction studies using rats, rabbits and mice, with cimetidine doses of up to 40 times the usual human dose. Because of its antiandrogenic properties, cimetidine has been reported to reduce sperm counts in males, and prostate and seminal vesicles in animals. The use of cimetidine in pregnancy requires that the potential benefit of the drug be weighed against the possible risk to the fetus.
Nursing Women
Cimetidine distributes into breast milk. Limited evidence suggests that the infant doses resulting from maternal cimetidine breast milk levels are much less than neonatal doses of 5 to 10 mg/kg daily. The clinical significance of an infant ingesting cimetidine from the milk, however, is currently unknown. Adverse effects to the fetus have not been reported. The American Academy of Pediatrics lists cimetidine as compatible with breastfeeding. Because of the potential of cimetidine to affect the metabolism of other drugs given concomitantly, nizatidine and famotidine may be preferred as they concentrate to a lesser degree in the breast milk [Clin Pharm 1991;10(8):594-624].
Cardiovascular
Cimetidine has been associated with sinus bradycardia.
Action and Clinical Pharmacology
Distribution
Cimetidine is 15 to 20% bound to plasma proteins. Cimetidine crosses the placenta. It also distributes into breast milk. Volume of distribution ranges from 0.8 to 1.3 L/kg which is also age-dependent, decreasing with increasing age.
Pharmacokinetics
Absorption
Cimetidine is rapidly and well absorbed following oral administration. Oral bioavailability is between 60 and 70%. When cimetidine is taken with meals, its absorption is delayed and slightly decreased; however, cimetidine is administered with food because peak concentrations and therefore maximal antisecretory effects of cimetidine are achieved when the stomach is no longer protected by the buffering capacity of food. The onset of action of cimetidine ranges from 15 to 60 minutes. Duration of action ranges from 4 to 8 hours.
Mechanism of Action
By competitively inhibiting histamine at the H2-receptor, cimetidine reduces gastric acid secretion under basal conditions and when stimulated with food or caffeine. In patients with peptic ulcer disease or Zollinger-Ellison syndrome, the basal gastric acid secretions are inhibited to a greater extent than meal-stimulated acid secretion at a given blood concentration of cimetidine.
Excretion
Cimetidine is primarily excreted in the urine as unchanged drug. In patients with normal renal function, the elimination half-life of cimetidine is 2 hours. In patients with creatinine clearance of 20 to 50 mL/min, the half-life is 2.9 hours. In patients with creatinine clearance of less than 20 mL/min, the half-life is 3.7 hours. In patients who are anephric, the half-life of cimetidine is 5 hours.
Adults
Metabolism
Cimetidine is metabolized in the liver to sulfoxide and 5-hydroxymethyl derivatives and may represent 25 to 40% of the total elimination of cimetidine.
Contraindications
Patients who are hypersensitive to cimetidine or to any ingredient in the formulation.
