Cimetidine | Cimetidine HCl
Cimetidine has been used for the treatment and/or
prophylaxis of gastric, abomasal and duodenal ulcers, uremic gastritis,
stress-related or drug-induced erosive gastritis, esophagitis, duodenal gastric
reflux and esophageal reflux. It has also been employed to treat hypersecretory
conditions associated with gastrinomas and systemic mastocytosis. Cimetidine has
also been used investigationally as a immunomodulating agent (see doses) in
dogs.
Prototype
histamine-2 blocker used to reduce GI acid production
Contraindications:
hypersensitivity. Caution: geriatric patients, hepatic or renal insufficiency
Storage/Stability/Compatibility
Cimetidine products should be stored protected from
light and kept at room temperature. Do not refrigerate the injectable product as
precipitation may occur. Oral dosage forms should be stored in tight containers.
The cimetidine injectable product is compatible
with the commonly used IV infusions solutions, including amino acid (TPN)
solutions, but should be used within 48 hours of dilution. Cimetidine is also
reported to be compatible with the following drugs: acetazolamide sodium,
amikacin sulfate, atropine sulfate, carbenicillin disodium, cefoxitin sodium,
chlorothiazide sodium, clindamycin phosphate, colistimethate sodium,
dexamethasone sodium phosphate, digoxin, epinephrine, erythromycin lactobionate,
furosemide, gentamicin sulfate, heparin sodium, insulin (regular), isoproterenol
HCl, lidocaine HCl, lincomycin HCl, methylprednisolone sodium succinate,
nafcillin sodium, norepinephrine bitartrate, penicillin G potassium/sodium,
phytonadione, polymyxin B sulfate, potassium chloride, protamine sulfate,
quinidine gluconate, sodium nitroprusside, tetracycline HCl, vancomycin HCl,
verapamil HCl, and vitamin B complex (w/ or w/o C).
The following drugs are reported to be either
incompatible with cimetidine or data are conflicting: amphotericin B,
ampicillin sodium, cefamandole naftate, cefazolin sodium, cephalothin sodium,
and pentobarbital sodium. Compatibility is dependent upon factors such as pH,
concentration, temperature and diluents used.
Pharmacology
At the H2 receptors of the parietal cells,
cimetidine competitively inhibits histamine, thereby reducing gastric acid
output both during basal conditions and when stimulated by food, pentagastrin,
histamine or insulin. Gastric emptying time, pancreatic or biliary secretion,
and lower esophageal pressures are not altered by cimetidine. By decreasing the
amount of gastric juice produced, cimetidine also decreases the amount of pepsin
secreted.
Cimetidine has an apparent immunomodulating effect as it
has been demonstrated to reverse suppressor T cell-mediated immune suppression.
It also possesses weak anti-androgenic activity.
Pharmacokinetics
Pharmacokinetic data for veterinary species is limited
for this agent. In dogs, the oral bioavailability is reported to be
approximately 95%, serum half-life is 1.3 hours and volume of distribution is
1.2 L/kg.
In humans, cimetidine is rapidly and well absorbed after
oral administration, but a small amount is metabolized in the liver before
entering the systemic circulation (first-pass effect). The oral bioavailability
is 70-80%. Food may delay absorption and slightly decrease the amount absorbed,
but when given with food, peak levels occur when the stomach is not protected by
the buffering capabilities of the ingesta.
Cimetidine is well distributed in body tissues and only
15-20% is bound to plasma proteins. The drug enters milk and crosses the
placenta.
Cimetidine is both metabolized in the liver and excreted
unchanged by the kidneys. More of the drug is excreted by the kidneys when
administered parenterally (75%) than when given orally (48%). The average serum
half-life is 2 hours in humans, but can be prolonged in elderly patients and in
those with renal or hepatic disease. Peritoneal dialysis does not appreciably
enhance the removal of cimetidine from the body.
Contraindications/Precautions
Cimetidine is contraindicated in patients with known
hypersensitivity to the drug.
Cimetidine should be used cautiously in geriatric patients
and in patients with significantly impaired hepatic or renal function. In humans
meeting these criteria, increased risk of CNS (confusion) effects may occur;
dosage reductions may be necessary.
Reproductive/Nursing Safety
In humans, the FDA categorizes this drug as category
B for use during pregnancy (Animal studies have not yet demonstrated risk
to the fetus, but there are no adequate studies in pregnant women; or animal
studies have shown an adverse effect, but adequate studies in pregnant women
have not demonstrated a risk to the fetus in the first trimester of pregnancy,
and there is no evidence of risk in later trimesters.) In a separate system
evaluating the safety of drugs in canine and feline pregnancy, this drug is
categorized as in class: B (Safe for use if used cautiously. Studies
in laboratory animals may have uncovered some risk, but these drugs appear to be
safe in dogs and cats or these drugs are safe if they are not administered when
the animal is near term.)
Adverse Effects/Warnings
Adverse effects appear to be very rare in animals at the
dosages generally used. Potential adverse effects (documented in humans) that
could be seen, include mental confusion, headache (upon discontinuation of the
drug), gynecomastia and decreased libido. Rarely, agranulocytosis may develop
and if given rapidly IV, transient cardiac arrhythmias may be seen. Pain at the
injection site may be noted after IM administration.
Cimetidine does inhibit microsomal enzymes in the liver
and may alter the metabolic rates of other drugs (see Drug Interactions below).
Overdosage
Clinical experience with cimetidine overdosage is
limited. In laboratory animals, very high dosages have been associated with
tachycardia and respiratory failure. Respiratory support and beta-adrenergic
blockers have been suggested for use should these symptoms occur.
Drug Interactions
Cimetidine may inhibit the hepatic microsomal enzyme
system and thereby reduce the metabolism, prolong serum half-lives, and increase
the serum levels of several drugs. It may also reduce the hepatic blood flow and
reduce the amount of hepatic extraction of drugs that have a high first-pass
effect. The following drugs may be affected: beta-blockers (e.g.,propranolol),
lidocaine, chloramphenicol, quinidine, calcium channel blockers (e.g.,verapamil),
diazepam (and other benzodiazepines), ethanol, metronidazole, phenytoin,
quinidine, theophylline, and warfarin. Dosage adjustment or increased
therapeutic monitoring may be necessary.
Cimetidine may decrease the renal clearance of
procainamide.
Cimetidine may exacerbate leukopenias when used with other
agents that can cause this problem.
Stagger doses (separate by 2 hours if possible) of
cimetidine with antacids, metoclopramide, sucralfate, digoxin, and
ketoconazole.
Drug/Laboratory Interactions
Cimetidine may cause small increases in plasma
creatinine concentrations early in therapy. These increases are generally
mild, non-progressive, and have disappeared when therapy is
discontinued.Histamine2 blockers may antagonize the effects of
histamine and pentagastrin in the evaluation gastric acid secretion.
After using allergen extract skin tests, histamine2
antagonists may inhibit histamine responses. It is recommended that histamine2
blockers be discontinued at least 24 hours before performing either of these
tests.
Doses
Dogs
For esophagitis:
1. 5-10 mg/kg PO q6h (do not give with antacids)
2. 4 mg/kg PO qid
For prevention of drug-induced gastric
erosion/ulceration:
1. 5 mg/kg PO, SC, tid
For chronic gastritis:
1. 5-10 mg/kg PO, IM or IV tid-qid
For ulcer disease:
1. 5-10 mg/kg PO, IM or IV tid-qid
2. 4-5 mg/kg PO, IV, or SC tid-qid
3. 5 mg/kg IV or PO qid
4. 5-10 mg/kg PO q6-8h or 10 mg/kg q6h as a slow (over 30
minutes) IV infusion
5. 10 mg/kg PO, IM, IV q8h
For gastrinoma:
1. 5-10 mg/kg PO, SC, IV q6-8h
To prevent histamine-mediated gastric
hyperacidity/ulceration secondary to mast cell tumors:
1. 5 mg/kg q8h
2. 5 mg/kg PO, IV, tid-qid
To decrease gastric acid hypersecretion during the
treatment of alkalosis:
1. 5-10 mg/kg tid-qid
As an immunomodulating agent (reverses suppressor T
cell-mediated immune suppression):
1. 10-25 mg/kg PO bid
Cats
1. 5-10 mg/kg PO q6-8h or 10 mg/kg q6h as a slow (over 30
minutes) IV infusion
Ferrets
1. For stress induced ulcers: 5-10 mg/kg PO, SC, IM or IV 3
times daily
Rabbits/Rodents/Pocket Pets
1. Rabbits: For GI ulcers: 5-10 mg/kg PO, SC, IM or
IV q8-12h
2. Mice, Rats, Gerbils, Hamsters,
Guinea pigs, Chinchillas: 5-10 mg/kg PO, IM or SC q6-12h
Cattle
To treat abomasal ulcers: 8-16 mg/kg tid (method
of administration not specified); relatively expensive and may be only of
minimal value
Horses: Note ARCI UCGFS Class 5 Drug
For foals:
1. 1000 mg divided bid or tid PO, IV or IM
2. 300-600 mg PO or IV 4 times a day
Swine
To treat gastric ulcers:
1. 300 mg per animal twice daily
Reptiles
In most species:
1. 4 mg/kg PO q8-12h
Monitoring Parameters
1) Clinical efficacy (dependent on reason for use);
monitored by decrease in symptomatology, endoscopic examination, blood in feces,
etc.; 2) Adverse effects if noted
Client Information
To maximize the benefit of this medication, it must be
administered as prescribed by the veterinarian; symptoms may reoccur if dosages
are missed.
Dosage Forms/Approval Status/Withholding Times
Veterinary-Approved Products: None
Human-Approved Products:
Cimetidine Tablets: 200 mg, 300 mg, 400 mg, 800 mg;
Tagamet® (SK-Beecham); (Rx); generic; (Rx)