Histamine H2 - Receptor Inhibitor
Cimetidine is a specific competitive histamine H2receptor antagonist which
effectively inhibits gastric acid secretion. It is advocated for the
treatment of conditions where the inhibition of gastric acid secretion is
likely to be beneficial. It competitively inhibits the action of histamine
at the histamine H2-receptors of the parietal cells and , thus, represents a
new class of pharmacological agent, the histamine H2-receptor antagonist.
Administered orally or i.v., cimetidine inhibits both daytime and nocturnal
basal (non-stimulated) gastric acid secretion. Cimetidine significantly
reduces gastric acid secretion stimulated by solid or liquid meals as well
as that stimulated by histamine, pentagastrin, caffeine, or insulin
infusion. It is generally much less effective in inhibiting carbachol (Carbarryl-choline
chloride) stimulated acid secretion. The extent of inhibition is
dose-related. A 50% reduction in gastric acid secretion is obtained by doses
of cimetidine giving a blood concentration of 1 to 2 umol/L (0.25 to 5 ug/mL).
Cimetidine reduces both hydrogen ion concentration and volume of gastric
secretion. Addition of an anticholinergic agent to cimetidine at dosages
greater than 400mg does not significantly enhance inhibition of acid output.
Pepsin output is decreased by cimetidine, largely due to reduced volume, but
to a lesser extent than acid output in the same patients. Cimetidine does
not consistently alter gastric emptying or lower esophageal sphincter
pressure. Pancreatic secretion of bicarbonate and enzymes is not influenced
by cimetidine. Cimetidine is readily absorbed after oral administration; bio
availability is about 70%. The plasma half-life is approximately 2 hours,
and most of a dose of cimetidine is recovered in the urine within 24 hours.
For the treatment of duodenal ulcer therapy and prophylaxis of recurrent
duodenal ulcer; non-malignant gastric ulcer; gastroesophageal reflux
disease; management of upper gastrointestinal hemorrhage; control of gastric
hypersecretion and peptic ulceration in the Zollinger-Ellison syndrome; and
prophylaxis of stress ulceration.
Contraindications: None known.
Exclude the presence of malignant gastrointestinal neoplasm before treating
symptoms of peptic ulceration with cimetidine. Because cimetidine is
excreted in the urine, reduced dose is usually necessary in patients with
impaired renal function. Cimetidine is removed by hemodialysis.
Pregnancy and Lactation: Give cimetidine to pregnant women only
when, in the judgment of the physician, potential benefits outweigh possible
risks. Give cimetidine with caution to nursing mothers; it is excreted in
Children: Clinical experience is limited; therefore, cimetidine
therapy cannot be recommended for children unless anticipated benefits
outweigh the potential risks. In very limited experience, 20 to 40 mg/kg/day
has been administered in divided doses by mouth or i.v
In therapeutic trials, cimetidine has been administered concomitantly with
sedatives, analgesics. thiazide diuretics, bronchodilators, digoxin and
propranolol without evidence of significant drug interaction. In patients on
coumarin-type anticoagulants, however, further prolongation of prothrombin
time has been observed with concomitant cimetidine administration. For this
reason, monitor closely and adjust the anticoagulant dose as necessary when
administering these drugs concurrently. Cimetidine impairs microsomal
oxidative drug metabolism in a dose-dependent manner in a rat model. The
inhibition was cimetidine inhibits microsomal drug metabolism.
Mild and transient diarrhea, muscular pain, dizziness and rash have been
reported in a small number of patients during treatment with cimetidine. A
few cases of reversible confusional states have been reported, usually in
elderly, severely ill patients, such as those with renal insufficiency or
organic brain syndrome. Overdosage may have played a role in some cases.
These confusional states generally cleared within 24 hours of drug
withdrawal. There have been reports that a few patients have developed mild
nonprogressive gynecomastia during prolonged treatment. No evidence of
induced endocrine dysfunction was found, and the condition remained
unchanged with continuing treatment. Rare cases of fever, hepatitis,
pancreatitis, and interstitial nephritis which cleared on drug withdrawal
have been reported. Some increased in plasma creatinine and serum
transaminase have been reported. Decreased white blood cell counts including
rare cases of agranulocytosis have been reported. These patients generally
had serious concomitant illness and were receiving drugs and/or treatment
known to produce neutropenia.
Hematologic Toxicity: Recently, cimetidine has been implicated in the
development of cases of agranulocytosis, pancytopenia and thrombocytopenia.
However, three patients recovering from metiamideinduced agranulocytosis,
continued to improve after beginning treatment with cimetidine. Of the
reports of bone-marrow depression reviewed, cimetidine cannot definitely by
implicated in any instance.
Symptoms: In cases reported to date, involving oral ingestion of up
to 12g of cimetidine per day for 5 days, no untoward effects were noted;
recovery was uneventful.
Treatment: Employ the usual measures to remove unabsorbed material
from the gastrointestinal tract, including clinical monitoring and
supportive therapy. Studies in animals indicate that assisted respiration
maybe of value and that any tachycardia may be controlled by administration
of a B-blocker
Dosage: In clinical studies, cimetidine has been used in divided
doses of up to 2400 mg/day in adults. Experience with cimetidine in children
is limited and has not been evaluated in clinical studies (see Precautions)
Duodenal ulcer: Adults: 300mg 4 times a day, with meals and at
bedtime. There has been considerable experience with a 200mg dose. A regimen
of 200mg three times daily taken with meals and 400mg at bedtime is
effective in treating benign gastric and duodenal ulceration. Although
healing with cimetidine often occurs during the first week or two, continue
treatment for at least 4 to 6 weeks, unless healing has been demonstrated by
endoscopic examination. Use daily maintenance therapy for patients who will
benefit from a reduction of gastric acid secretion, as well as for patients
known to suffer frequent recurrence of duodenal ulcers. Following healing,
initiate maintenance therapy for periods of 6 to 12 months at a reduced
dosage with the last daily dose taken at bedtime. Reassess patients
periodically after this period of maintenance preferably by endoscopy.
Non-malignant gastric ulcer and gastroesophageal reflux disease:
Adults: 300mg 4 times daily with meals and at bedtime. Although healing of a
non-malignant gastric ulcer may occur within the first 2 weeks, continue
treatment for at least 6 weeks, unless healing has been demonstrated
endoscopically. Administer antacids with caution concomitantly if required.
Management of upper g.i. hemorrhage: Adults: 300mg every 6 hours.
In some patients it may be necessary to increase dosage; however, do not
exceed a total daily dosage of 2400mg.
Impaired renal function: Patients with moderate or sever renal
impairment should receive an initial dose if 200 or 300mg every 12 hours. If
any increase in dosage is necessary, increase the frequency of
For patients undergoing hemodialysis, perform dialysis just prior to the
next scheduled dose, as some drug will be removed by dialysis.
Pathological hypersecretory conditions: e.g Zollinger-Ellison Syndrome
: Adults : 300mg 4 times daily with meals and at bedtime, or 200mg 3
times daily wit meals and 400mg at night. Some patients may require more
frequent administration or higher individual doses to control symptoms.
Adjust dosage to patient's needs; do not exceed 2400mg/day.
Availability of dosage forms:
Each pale green, biconvex, round, film-coated tablets, one side engraved
"APO" over "200" uniform very slightly off white core contains cimetidine
200mg. Available in PVC blisters of 500 tablets.
Each pale green, oblong, biconvex, film-coated tablets, one side engraved
"APO-400" contains cimetidine 400mg. Available in PVC blisters of 500
Protect from light. Store between 15-30°C.
3 years from date of manufacture.