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Cimetidine Injection (Cimetidine Injection) - Description and Clinical Pharmacology


in 0.9% Sodium Chloride Injection, USP

300 mg (6 mg/mL) Cimetidine

Flexible Plastic Container

For Intravenous Infusion Only

Rx only


Cimetidine in 0.9% Sodium Chloride Injection, USP is a sterile, nonpyrogenic solution of cimetidine hydrochloride in 0.9% sodium chloride injection. It is administered by the intravenous route. Each mL contains cimetidine HCl equivalent to 6 mg cimetidine and sodium chloride 9 mg in water for injection. The osmolar concentration is 356 mOsmol/L (calc.); pH is 6.0 (5.0 to 7.0). May contain hydrochloric acid and/or sodium hydroxide for pH adjustment. The solution contains no bacteriostat, antimicrobial agent or added buffer and is intended only for use as a single-dose administration. When smaller doses are required, the unused portion should be discarded.

Cimetidine hydrochloride is a histamine H2-receptor antagonist. Chemically it is N" -cyano- N -methyl- N' -[2-[[(5-methyl-1 H -imidazol-4-yl)methyl]thio]-ethyl]-guanidine.

The molecular formula for cimetidine hydrochloride is C10H16N6S•HCl and the molecular weight is 288.80. The structural formula of cimetidine hydrochloride is:

Cimetidine Hydrochloride

Cimetidine contains an imidazole ring, and is chemically related to histamine.

Cimetidine hydrochloride has a bitter taste and characteristic odor.

Sodium Chloride, USP is chemically designated NaCI, a white crystalline compound freely soluble in water.

Water for Injection, USP is chemically designated H2O.

The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. Exposure to temperatures above 25°C/77°F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period.


Cimetidine competitively inhibits the action of histamine at the histamine H2 receptors of the parietal cells and thus is a histamine H2-receptor antagonist.

Cimetidine is not an anticholinergic agent. Studies have shown that cimetidine inhibits both daytime and nocturnal basal gastric acid secretion. Cimetidine also inhibits gastric acid secretion stimulated by food, histamine, pentagastrin, caffeine and insulin.

Antisecretory Activity

  1. Acid Secretion: Nocturnal: Cimetidine 800 mg orally at bedtime reduces mean hourly H+ activity by greater than 85% over an eight-hour period in duodenal ulcer patients, with no effect on daytime acid secretion. Cimetidine 1600 mg orally h.s. produces 100% inhibition of mean hourly H+ activity over an eight-hour period in duodenal ulcer patients, but also reduces H+ activity by 35% for an additional five hours into the following morning. Cimetidine 400 mg b.i.d. and 300 mg q.i.d. decrease nocturnal acid secretion in a dose-related manner, i.e., 47% to 83% over a six- to eight-hour period and 54% over a nine-hour period, respectively.

    Food Stimulated: During the first hour after a standard experimental meal, oral cimetidine 300 mg inhibited gastric acid secretion in duodenal ulcer patients by at least 50%. During the subsequent two hours cimetidine inhibited gastric acid secretion by at least 75%.

    The effect of a 300 mg breakfast dose of cimetidine continued for at least four hours and there was partial suppression of the rise in gastric acid secretion following the luncheon meal in duodenal ulcer patients. This suppression of gastric acid output was enhanced and could be maintained by another 300 mg dose of cimetidine given with lunch.

    In another study, cimetidine 300 mg given with the meal increased gastric pH as compared with placebo.

    Mean Gastric pH



    1 hour



    2 hours



    3 hours



    4 hours



    24-Hour Mean H + Activity: Cimetidine 800 mg h.s., 400 mg b.i.d. and 300 mg q.i.d. all provide a similar, moderate (less than 60%) level of 24 hour acid suppression. However, the 800 mg h.s. regimen exerts its entire effect on nocturnal acid, and does not affect daytime gastric physiology.

    Chemically Stimulated: Oral cimetidine significantly inhibited gastric acid secretion stimulated by betazole (an isomer of histamine), pentagastrin, caffeine and insulin as follows:


    Stimulant Dose


    % Inhibition


    1.5 mg/kg (sc)

    300 mg (po)

    85% at 2½ hours


    6 mcg/kg/hr (iv)

    100 mg/hr (iv)

    60% at 1 hour


    5 mg/kg/hr (iv)

    300 mg (po)

    100% at 1 hour


    0.03 units/kg/hr (iv)

    100 mg/hr (iv)

    82% at 1 hour

    When food and betazole were used to stimulate secretion, inhibition of hydrogen ion concentration usually ranged from 45 to 75% and the inhibition of volume ranged from 30 to 65%.

    Parenteral administration also significantly inhibits gastric acid secretion. In a crossover study involving patients with active or healed duodenal or gastric ulcers, either continuous I.V. infusion of cimetidine 37.5 mg/hour (900 mg/day) or intermittent injection of cimetidine 300 mg q6h (1200 mg/day) maintained gastric pH above 4.0 for more than 50% of the time under steady-state conditions.

  2. Pepsin: Oral cimetidine 300 mg reduced total pepsin output as a result of the decrease in volume of gastric juice.

  3. Intrinsic Factor: Intrinsic factor secretion was studied with betazole as a stimulant. Oral cimetidine 300 mg inhibited the rise in intrinsic factor concentration produced by betazole, but some intrinsic factor was secreted at all times.


Lower Esophageal Sphincter Pressure and Gastric Emptying

Cimetidine has no effect on lower esophageal sphincter (LES) pressure or the rate of gastric emptying.


Cimetidine is rapidly absorbed after oral administration and peak levels occur in 45 to 90 minutes. The half-life of cimetidine is approximately 2 hours. Both oral and parenteral (I.V. or I.M.) administration provide comparable periods of therapeutically effective blood levels; blood concentrations remain above that required to provide 80% inhibition of basal gastric acid secretion for 4 to 5 hours following a dose of 300 mg.

Steady-state blood concentrations of cimetidine with continuous infusion of cimetidine hydrochloride are determined by the infusion rate and clearance of the drug in the individual patient. In a study of peptic ulcer patients with normal renal function, an infusion rate of 37.5 mg/hour produced average steady-state plasma cimetidine concentrations of about 0.9 mcg/mL. Blood levels with other infusion rates will vary in direct proportion to the infusion rate.

The principal route of excretion of cimetidine is the urine. Following parenteral administration, most of the drug is excreted as the parent compound; following oral administration, the drug is more extensively metabolized, the sulfoxide being the major metabolite. Following a single oral dose, 48% of the drug is recovered from the urine after 24 hours as the parent compound. Following I.V. or I.M. administration, approximately 75% of the drug is recovered from the urine after 24 hours as the parent compound.

Sodium chloride in water dissociates to provide sodium (Na+) and chloride (Cl¯) ions. Sodium (Na+) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Chloride (Cl¯) has an integral role in buffering action when oxygen and carbon dioxide exchange occurs in the red blood cells. The distribution and excretion of sodium (Na+) are largely under the control of the kidney which maintains a balance between intake and output.

Water is an essential constituent of all body tissues and accounts for approximately 70% of total body weight.

Average normal adult daily requirements range from two to three liters (1.0 to 1.5 liters each for insensible water loss by perspiration and urine production).

Waterbalance is maintained by various regulatory mechanisms. Water distribution depends primarily on the concentration of electrolytes in the body compartments and sodium (Na+) plays a major role in maintaining physiologic equilibrium.

Clinical Trials

Duodenal Ulcer

Cimetidine has been shown to be effective in the treatment of active duodenal ulcer and, at reduced dosage, in maintenance therapy following healing of active ulcers.

Active Duodenal Ulcer: Cimetidine accelerates the rate of duodenal ulcer healing. Healing rates reported in U.S. and foreign controlled trials with oral cimetidine are summarized below, beginning with the regimen providing the lowest nocturnal dose.

Duodenal Ulcer Healing Rates with Various Cimetidine Dosage Regimens*


300 mg q.i.d.

400 mg b.i.d.

800 mg h.s.

1600 mg h.s.

week 4





week 6




week 8



*Averages from controlled clinical trials.

A U.S., double-blind, placebo-controlled, dose-ranging study demonstrated that all once-daily at bedtime (h.s.) cimetidine regimens were superior to placebo in ulcer healing and that cimetidine 800 mg h.s. healed 75% of patients at four weeks. The healing rate with 800 mg h.s. was significantly superior to 400 mg h.s. (66%) and not significantly different from 1600 mg h.s. (81%).

In the U.S. dose-ranging trial, over 80% of patients receiving cimetidine 800 mg h.s. experienced nocturnal pain relief after one day. Relief from daytime pain was reported in approximately 70% of patients after two days. As with ulcer healing, the 800 mg h.s. dose was superior to 400 mg h.s. and not different from 1600 mg h.s.

In foreign, double-blind studies with cimetidine 800 mg h.s., 79% to 85% of patients were healed at four weeks.

While short-term treatment with cimetidine can result in complete healing of the duodenal ulcer, acute therapy will not prevent ulcer recurrence after cimetidine has been discontinued. Some follow-up studies have reported that the rate of recurrence once therapy was discontinued was slightly higher for patients healed on cimetidine than for patients healed on other forms of therapy; however, the cimetidine-treated patients generally had more severe disease.

Maintenance Therapy in Duodenal Ulcer: Treatment with a reduced dose of cimetidine has been proven effective as maintenance therapy following healing of active duodenal ulcers.

In numerous placebo-controlled studies conducted worldwide, the percent of patients with observed ulcers at the end of one year's therapy with cimetidine 400 mg h.s. was significantly lower (10 to 45%) than in patients receiving placebo (44% to 70%). Thus, from 55% to 90% of patients were maintained free of observed ulcers at the end of one year with cimetidine 400 mg h.s.

Factors such as smoking, duration and severity of disease, gender, and genetic traits may contribute to variations in actual percentages.

Trials of other anti-ulcer therapy, whether placebo-controlled, positive-controlled or open, have demonstrated a range of results similar to that seen with cimetidine.

Active Benign Gastric Ulcer

Cimetidine has been shown to be effective in the short-term treatment of active benign gastric ulcer.

In a multicenter, double-blind U.S. study, patients with endoscopically confirmed benign gastric ulcer were treated with cimetidine 300 mg four times a day or with placebo for six weeks. Patients were limited to those with ulcers ranging from 0.5 to 2.5 cm in size. Endoscopically confirmed healing at six weeks was seen in significantly* more cimetidine-treated patients than in patients receiving placebo, as shown below:



week 2

14/63 (22%)

7/63 (11%)

total at week 6

43/65 (66%)*

30/67 (45%)


In a similar multicenter U.S. study of the 800 mg h.s. oral regimen, the endoscopically confirmed healing rates were:



total at week 6

63/83 (76%)*

44/80 (55%)


Similarly, in worldwide double-blind clinical studies, endoscopically evaluated benign gastric ulcer healing rates were consistently higher with cimetidine than with placebo.

Preventionof Upper Gastrointestinal Bleeding in Critically Ill Patients

A double-blind, placebo-controlled randomized study of continuous infusion cimetidine was performed in 131 critically ill patients (mean APACHE II score = 15.99) to compare the incidence of upper gastrointestinal bleeding, manifested as hematemesis or bright red blood which did not clear after adjustment of the nasogastric tube and a 5 to 10 minute lavage, persistent Gastroccult (R) positive coffee grounds for 8 consecutive hours which did not clear with 100 cc lavage and/or which were accompanied by a drop in hematocrit of 5 percent points, or melena, with an endoscopically documented upper gastrointestinal source of bleed. 14% (9/65) of patients treated with cimetidine continuous infusion developed bleeding compared to 33% (22/66) of the placebo group. Coffee grounds was the manifestation of bleeding that accounted for the difference between groups. Another randomized, double-blind placebo-controlled study confirmed these results for an end point of upper gastrointestinal bleeding with a confirmed upper gastrointestinal source noted on endoscopy, and by post hoc analyses of bleeding episodes between groups.

Pathological Hypersecretory Conditions (such as Zollinger-Ellison Syndrome)

Cimetidine significantly inhibited gastric acid secretion and reduced occurrence of diarrhea, anorexia and pain in patients with pathological hypersecretion associated with Zollinger-Ellison Syndrome, systemic mastocytosis and multiple endocrine adenomas. Use of cimetidine was also followed by healing of intractable ulcers.

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