Cimetidine

Cimetidine - Tagamet ®

Usual Diluents

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

----Continuous infusion----
[900 mg/ 100 to 250 ml] [24 hour]
[901 to 2400mg/ 250-1000 ml] [24 hour]

Stability / Miscellaneous

Renal dosing: >40/ q6h; 20 to 40/ q8h; 5 to 20/q12h; <5/200 mg q12h.

DOSAGE AND ADMINISTRATION
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.

The doses and regimen for parenteral administration in patients with GERD have not been established.

Recommendations for Parenteral Administration:
Intramuscular Injection: 300 mg every 6 to 8 hours (no dilution necessary). Transient pain at the site of injection has been reported.

Intravenous Injection: 300 mg every 6 to 8 hours. 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. Dilute Cimetidine Injection, USP, 300 mg, in Sodium Chloride Injection (0.9%) or another compatible I.V. solution (see Stability of Cimetidine Injection, USP) to a total volume of 20 mL and inject over a period of not less than 5 minutes (see PRECAUTIONS).

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.

Dilute Cimetidine Injection, USP, 300 mg, in at least 50 mL of 5% Dextrose Injection, or another compatible I.V. solution (see Stability of Cimetidine Injection, USP).

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. Dilute 900 mg Cimetidine Injection, USP in a compatible I.V. fluid (see Stability of Cimetidine Injection, USP) for constant rate infusion over a 24-hour period. Note: Cimetidine Injection, USP may be diluted in 100 to 1000 mL; however, 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.

Stability of Cimetidine Injection, USP
When added to or diluted with most commonly used intravenous solutions, e.g., Sodium Chloride Injection (0.9%), Dextrose Injection (5% or 10%), Lactated Ringer’s Injection, 5% Sodium Bicarbonate Injection, Cimetidine Injection, USP should not be used after more than 48 hours of storage at room temperature.

NOTE: The products accompanying this insert are for I.M./I.V. use 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 (see Clinical Trials—Active Duodenal Ulcer). 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 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 and 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 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 administer product unless solution is clear and container is undamaged. Discard unused portion. All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HOW SUPPLIED
Cimetidine Injection, USP 300 mg/2 mL cimetidine is supplied as follows:
Single-dose Fliptop Vial - 2 mL;
Multiple-dose Fliptop Vial - 8 mL.

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Do not refrigerate.

August, 2006
©Hospira 2006 EN-1270
Hospira, Inc., Lake Forest, IL 60045 USA

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Stability
Intact vials of cimetidine should be stored at room temperature and protected from light; cimetidine may precipitate from solution upon exposure to cold but can be redissolved by warming without degradation

Stability at room temperature:
Prepared bags: 7 days

Premixed bags: Manufacturer expiration dating and out of overwrap stability: 15 days.