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)