Cimetidine (injection)

Cimetidine (injection)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

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Overview

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Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

• Short-term treatment of active duodenal ulcer. Most patients heal within 4 weeks and there is rarely reason to use cimetidine at full dosage for longer than 6 to 8 weeks. Concomitant antacids should be given as needed for relief of pain. However, simultaneous administration of oral cimetidine and antacids is not recommended, since antacids have been reported to interfere with the absorption of oral cimetidine.

• Maintenance therapy for duodenal ulcer patients at reduced dosage after healing of active ulcer. Patients have been maintained on continued treatment with cimetidine 400 mg h.s. for periods of up to five years.

• Short-term treatment of active benign gastric ulcer. There is no information concerning usefulness of treatment periods of longer than 8 weeks.

• Prevention of upper gastrointestinal bleeding in critically ill patients.

• The treatment of pathological hypersecretory conditions (i.e., Zollinger-Ellison Syndrome, systemic mastocytosis, multiple endocrine adenomas).

Dosage

Parenteral Administration

• In hospitalized patients with pathological hypersecretory conditions or intractable ulcers, or in patients who are unable to take oral medication, cimetidine may be administered parenterally.

• Intermittent Intravenous Infusion: 300 mg every 6 to 8 hours, infused over 15 to 20 minutes. In some patients it may be necessary to increase dosage. When this is necessary, the increases should be made by more frequent administration of a 300 mg dose, but should not exceed 2400 mg per day.

• Continuous Intravenous Infusion: 37.5 mg/hour (900 mg/day). For patients requiring a more rapid elevation of gastric pH, continuous infusion may be preceded by a 150 mg loading dose administered by I.V. infusion as described above. Note: A volumetric pump is recommended if the volume for 24-hour infusion is less than 250 mL. In one study in patients with pathological hypersecretory states, the mean infused dose of cimetidine was 160 mg/hour with a range of 40 to 600 mg/hour.

• These doses maintained the intragastric acid secretory rate at 10 mEq/hour or less. The infusion rate should be adjusted to individual patient requirements.

NOTE: The products accompanying this insert are for I.V. infusion only. Much of the following relates to the use of oral cimetidine and is for informational purposes only. See Parenteral Administration (above) for specific dosing recommendations.

Duodenal Ulcer

• Active Duodenal Ulcer: Clinical studies have indicated that suppression of nocturnal acid is the most important factor in duodenal ulcer healing. This is supported by recent clinical trials. Therefore, there is no apparent rationale, except for familiarity with use, for treating with anything other than a once-daily at bedtime oral dosage regimen (h.s.).

• In a U.S. oral dose-ranging study of 400 mg h.s., 800 mg h.s. and 1600 mg h.s., a continuous dose response relationship for ulcer healing was demonstrated.

• However, 800 mg h.s. is the dose of choice for most patients, as it provides a high healing rate (the difference between 800 mg h.s. and 1600 mg h.s. being small), maximal pain relief, a decreased potential for drug interactions (see PRECAUTIONS − Drug Interactions) and maximal patient convenience. Patients unhealed at four weeks, or those with persistent symptoms, have been shown to benefit from two to four weeks of continued therapy.

• It has been shown that patients who both have an endoscopically demonstrated ulcer larger than 1 cm and are also heavy smokers (i.e., smoke one pack of cigarettes or more per day) are more difficult to heal. There is some evidence which suggests that more rapid healing can be achieved in this subpopulation with cimetidine 1600 mg at bedtime. While early pain relief with either 800 mg h.s. or 1600 mg h.s. is equivalent in all patients, 1600 mg h.s. provides an appropriate alternative when it is important to ensure healing within four weeks for this subpopulation. Alternatively, approximately 94% of all patients will also heal in eight weeks with cimetidine 800 mg h.s.

• Other cimetidine oral regimens in the U.S. which have been shown to be effective are: 300 mg four times daily, with meals at bedtime, the original regimen with which U.S. physicians have the most experience, and 400 mg twice daily, in the morning and at bedtime (see Clinical Trials−Active Duodenal Ulcer).

• Concomitant antacids should be given as needed for relief of pain. However, simultaneous administration of oral cimetidine and antacids is not recommended, since antacids have been reported to interfere with the absorption of oral cimetidine.

• While healing with cimetidine often occurs during the first week or two, treatment should be continued for 4 to 6 weeks unless healing has been demonstrated by endoscopic examination.

• Maintenance Therapy for Duodenal Ulcer: In those patients requiring maintenance therapy, the recommended adult oral dose is 400 mg at bedtime.

Active Benign Gastric Ulcer

• The recommended adult oral dosage for short-term treatment of active benign gastric ulcer is 800 mg h.s., or 300 mg four times a day with meals and at bedtime. Controlled clinical studies were limited to six weeks of treatment (see Clinical Trials). 800 mg h.s. is the preferred regimen for most patients based upon convenience and reduced potential for drug interactions. Symptomatic response to cimetidine does not preclude the presence of a gastric malignancy. It is important to follow gastric ulcer patients to assure rapid progress to complete healing.

Prevention of Upper Gastrointestinal Bleeding

• The recommended adult dosing regimen is continuous I.V. infusion of 50 mg/hour. Patients with creatinine clearance less than 30 cc/min. should receive half the recommended dose. Treatment beyond 7 days has not been studied.

Pathological Hypersecretory Conditions (such as Zollinger−Ellison Syndrome)

• Recommended adult oral dosage: 300 mg four times a day with meals and at bedtime. In some patients it may be necessary to administer higher doses more frequently. Doses should be adjusted to individual patient needs, but should not usually exceed 2400 mg per day and should continue as long as clinically indicated.

Dosage Adjustment for Patients with Impaired Renal Function

• Patients with severely impaired renal function have been treated with cimetidine. However, such usage has been very limited. On the basis of this experience the recommended dosage is 300 mg every 12 hours orally or by intravenous injection. Should the patient's condition require, the frequency of dosing may be increased to every 8 hours or even further with caution. In severe renal failure, accumulation may occur and the lowest frequency of dosing compatible with an adequate patient response should be used. When liver impairment is also present, further reductions in dosage may be necessary. Hemodialysis reduces the level of circulating cimetidine. Ideally, the dosage schedule should be adjusted so that the timing of a scheduled dose coincides with the end of hemodialysis.

• Patients with creatinine clearance less than 30 cc/min. who are being treated for prevention of upper gastrointestinal bleeding should receive half the recommended dose.

• Do not add other drugs to premixed Cimetidine in 0.9% Sodium Chloride Injection, USP in plastic containers.

• All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Cimetidine (injection) in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Cimetidine (injection) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Cimetidine (injection) in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Cimetidine (injection) in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Cimetidine (injection) in pediatric patients.

Contraindications

• Cimetidine is contraindicated for patients known to have hypersensitivity to the product.

Warnings

There is limited information regarding Cimetidine (injection) Warnings' in the drug label.

Adverse Reactions

Clinical Trials Experience

• Adverse effects reported in patients taking cimetidine are described below by body system. Incidence figures of 1 in 100 and greater are generally derived from controlled clinical studies.

• The collection of this information has been derived largely from trials associated with oral cimetidine.

• Gastrointestinal:

• Diarrhea (usually mild) has been reported in approximately 1 in 100 patients.

• CNS:

• Headaches, ranging from mild to severe, have been reported in 3.5% of 924 patients taking 1600 mg/day, 2.1% of 2,225 patients taking 800 mg/day and 2.3% of 1,897 patients taking placebo. Dizziness and somnolence (usually mild) have been reported in approximately 1 in 100 patients on either 1600 mg/day or 800 mg/day.

• Reversible confusional states, e.g., mental confusion, agitation, psychosis, depression, anxiety, hallucinations, disorientation, have been reported predominantly, but not exclusively, in severely ill patients. They have usually developed within 2 to 3 days of initiation of cimetidine therapy and have cleared within 3 to 4 days of discontinuation of the drug.

• Endocrine:

• Gynecomastia has been reported in patients treated for one month or longer. In patients being treated for pathological hypersecretory states, this occurred in about 4% of cases while in all others the incidence was 0.3% to 1% in various studies. No evidence of induced endocrine dysfunction was found, and the condition remained unchanged or returned toward normal with continuing cimetidine treatment.

• Reversible impotence has been reported in patients with pathological hypersecretory disorders, e.g., Zollinger−Ellison Syndrome, receiving cimetidine particularly in high doses, for at least 12 months (range 12 to 79 months, mean 38 months). However, in large-scale surveillance studies at regular dosage, the incidence has not exceeded that commonly reported in the general population.

• Hematologic:

• Decreased white blood cell counts in cimetidine-treated patients (approximately 1 per 100,000 patients), including agranulocytosis (approximately 3 per million patients), have been reported, including a few reports of recurrence on rechallenge. Most of these reports were in patients who had serious concomitant illnesses and received drugs and/or treatment known to produce neutropenia. Thrombocytopenia (approximately 3 per million patients) and, very rarely, cases of pancytopenia or aplastic anemiahave also been reported. As with some other H2 receptor antagonists, there have been extremely rare reports of immune hemolytic anemia.

• Hepatobiliary:

• Dose-related increases in serum transaminase have been reported. In most cases they did not progress with continued therapy and returned to normal at the end of therapy. There have been rare reports of cholestatic or mixed cholestatic hepatocellular effects. These were usually reversible. Because of the predominance of cholestatic features, severe parenchymal injury is considered highly unlikely. However, as in the occasional liver injury with other H2-receptor antagonists, in exceedingly rare circumstances fatal outcomes have been reported.

• There has been reported a single case of biopsy-proven periportal hepatic fibrosis in a patient receiving cimetidine.

• Rare cases of pancreatitis, which cleared on withdrawal of the drug, have been reported.

• Hypersensitivity:

• Rare cases of fever and allergic reactions including anaphylaxis and hypersensitivity vasculitis, which cleared on withdrawal of the drug, have been reported.

• Renal:

• Small, possibly dose-related increases in plasma creatinine, presumably due to competition for renal tubular secretion, are not uncommon and do not signify deteriorating renal function. Rare cases of interstitial nephritis and urinary retention, which cleared on withdrawal of the drug, have been reported.

• Cardiovascular:

• Rare cases of bradycardia, tachycardia and A-V heart block have been reported with H2-receptor antagonists.

• Musculoskeletal:

• There have been rare reports of reversible arthralgia and myalgia; exacerbation of joint symptoms in patients with preexisting arthritis has also been reported. Such symptoms have usually been alleviated by a reduction in cimetidine dosage. Rare cases of polymyositis have been reported, but no causal relationship has been established.

• Integumental:

• Mild rash and, very rarely, cases of severe generalized skin reactions including Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, exfoliative dermatitis and generalized exfoliative erythroderma have been reported with H2-receptor antagonists. Reversible alopecia has been reported very rarely.

• Immune Function:

• There have been extremely rare reports of strongyloidiasis hyperinfection in immunocompromised patients.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Cimetidine (injection) in the drug label.

Drug Interactions

• Cimetidine, apparently through an effect on certain microsomal enzyme systems, has been reported to reduce the hepatic metabolism of warfarin-type anticoagulants, phenytoin, propranolol, nifedipine, chlordiazepoxide, diazepam, certain tricyclic antidepressants, lidocaine, theophylline and metronidazole, thereby delaying elimination and increasing blood levels of these drugs.

• Clinically significant effects have been reported with the warfarin anticoagulants; therefore, close monitoring of prothrombin time is recommended, and adjustment of the anticoagulant dose may be necessary when cimetidine is administered concomitantly. Interaction with phenytoin, lidocaine and theophylline has also been reported to produce adverse clinical effects.

• However, a crossover study in healthy subjects receiving either cimetidine 300 mg q.i.d. or 800 mg h.s. concomitantly with a 300 mg b.i.d. dosage of theophylline extended-release tablets demonstrated less alteration in steady-state theophylline peak serum levels with the 800 mg h.s. regimen, particularly in subjects aged 54 years and older. Data beyond ten days are not available. (Note: All patients receiving theophylline should be monitored appropriately, regardless of concomitant drug therapy.)

• Dosage of the drugs mentioned above and other similarly metabolized drugs, particularly those of low therapeutic ratio or in patients with renal and/or hepatic impairment, may require adjustment when starting or stopping concomitantly administered cimetidine to maintain optimum therapeutic blood levels.

• Alteration of pH may affect absorption of certain drugs (e.g. ketoconazole). If these products are needed, they should be given at least 2 hours before cimetidine administration.

• Additional clinical experience may reveal other drugs affected by the concomitant administration of cimetidine.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Teratogenic Effects: Pregnancy Category B: Reproduction studies have been performed in rats, rabbits and mice at doses up to 40 times the normal human dose and have revealed no evidence of impaired fertility or harm to the fetus due to cimetidine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cimetidine (injection) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Cimetidine (injection) during labor and delivery.

Nursing Mothers

• Cimetidine is secreted in human milk and, as a general rule, nursing should not be undertaken while a patient is on a drug.

• Caution should be exercised when solutions from flexible plastic containers are administered to a nursing mother.

Pediatric Use

• Clinical experience in pediatric patients is limited. Therefore, cimetidine therapy cannot be recommended for pediatric patients under 16, unless, in the judgment of the physician, anticipated benefits outweigh the potential risks. In very limited experience, doses of 20 to 40 mg/kg per day have been used.

• Safety and effectiveness of solutions from flexible plastic containers in pediatric patients have not been well established.

Geriatic Use

There is no FDA guidance on the use of Cimetidine (injection) with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Cimetidine (injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Cimetidine (injection) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Cimetidine (injection) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Cimetidine (injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Cimetidine (injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Cimetidine (injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

• Oral

• Intravenous

Monitoring

There is limited information regarding Monitoring of Cimetidine (injection) in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Cimetidine (injection) in the drug label.

Overdosage

• Studies in animals indicate that toxic doses are associated with respiratory failure and tachycardia that may be controlled by assisted respiration and the administration of a beta blocker.

• Reported acute ingestions orally of up to 20 grams have been associated with transient adverse effects similar to those encountered in normal clinical experience. The usual measures to remove unabsorbed material from the gastrointestinal tract, clinical monitoring and supportive therapy, should be employed.

• There have been reports of severe CNS symptoms, including unresponsiveness, following ingestion of between 20 and 40 grams of cimetidine, and extremely rare reports following concomitant use of multiple CNS-active medications and ingestion of cimetidine at doses less than 20 grams. An elderly, terminally ill dehydrated patient with organic brain syndrome receiving concomitant antipsychotic agents and cimetidine 4800 mg intravenously over a 24 hour period experienced mental deterioration with reversal on cimetidine discontinuation.

• There have been two deaths in adults who have been reported to have ingested over 40 grams orally on a single occasion.

Pharmacology

There is limited information regarding Cimetidine (injection) Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Cimetidine (injection) Mechanism of Action in the drug label.

Structure

There is limited information regarding Cimetidine (injection) Structure in the drug label.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Cimetidine (injection) in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Cimetidine (injection) in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility:

• In a 24-month toxicity study conducted in rats, at dose levels of 150, 378 and 950 mg/kg/day (approximately 8 to 48 times the recommended human dose), there was a small increase in the incidence of benign Leydig cell tumors in each dose group: when the combined drug-treated groups and control groups were compared, this increase reached statistical significance. In a subsequent 24 month study, there were no differences between the rats receiving 150 mg/kg/day and the untreated controls. However, a statistically significant increase in benign Leydig cell tumor incidence was seen in the rats that received 378 and 950 mg/kg/day. These tumors were common in control groups as well as treated groups and the difference became apparent only in aged rats.

• Cimetidine has demonstrated a weak antiandrogenic effect. In animal studies this was manifested as reduced prostate and seminal vesicle weights. However, there was no impairment of mating performance or fertility, nor any harm to the fetus in these animals at doses 8 to 48 times the full therapeutic dose of cimetidine, as compared with controls. The cases of gynecomastia seen in patients treated for one month or longer may be related to this effect.

• In human studies, cimetidine has been shown to have no effect on spermatogenesis, sperm count, motility, morphology or in vitro fertilizing capacity.

• Studies with solutions from flexible plastic containers have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

Clinical Studies

There is limited information regarding Clinical Studies of Cimetidine (injection) in the drug label.

How Supplied

Storage

There is limited information regarding Cimetidine (injection) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Cimetidine (injection) in the drug label.

Precautions with Alcohol

• Alcohol-Cimetidine (injection) interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• CIMETIDINE IN SODIUM CHLORIDE®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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