Cimetidine

H2 receptor antagonist Gastrointestinal agent

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 5-10 mg/kg q8h or q12h Duration: 4-8 weeks for ulcers; as needed for other conditions
Notes: For mast cell tumors, use as adjunct to antihistamines. Reduce dose in renal impairment.
Cat PO 5-10 mg/kg q8h or q12h Duration: 4-8 weeks for ulcers; as needed
Notes: May cause CNS signs in cats; use with caution.
Horse PO 20 mg/kg q8h Duration: 4-6 weeks for gastric ulcers
Notes: Oral paste or tablet; may be less effective than proton pump inhibitors.
Cattle PO 8-16 mg/kg q8h Duration: 3-5 days
Notes: Off-label use; withdrawal times must be observed.
Small Ruminants PO 10 mg/kg q8h Duration: 3-5 days
Notes: Off-label use; withdrawal times must be observed.
Rabbit PO 5-10 mg/kg q12h Duration: As needed
Notes: Limited evidence; use with caution.
Bird/Poultry PO 10 mg/kg q12h Duration: As needed
Notes: Off-label; adjust for species.
Exotic/Other PO 5-10 mg/kg q12h Duration: As needed
Notes: Use with caution; limited data.

Clinical Indications & Species Uses

General Indications
  • Treatment of gastric and duodenal ulcers
  • Management of gastroesophageal reflux disease
  • Reduction of gastric acid secretion in conditions where acid suppression is beneficial
Dog (Canine)
  • Gastric and duodenal ulcers
  • Gastroesophageal reflux disease
  • Esophagitis
  • Mast cell tumor (as adjunct to reduce histamine-induced acid secretion)
  • Stress-related gastric ulceration
  • Zollinger-Ellison syndrome (rare)
Cat (Feline)
  • Gastric and duodenal ulcers
  • Gastroesophageal reflux disease
  • Esophagitis
  • Chronic gastritis
  • Mast cell tumor (adjunct)
Horse (Equine)
  • Gastric ulcers (equine gastric ulcer syndrome)
  • Esophagitis
  • Gastroesophageal reflux
Cattle (Bovine)
  • Abomasal ulcers
  • Indigestion with gastric hyperacidity
  • Adjunct in treatment of abomasal displacement (off-label)
Small Ruminants (Sheep / Goat)
  • Abomasal ulcers
  • Gastroesophageal reflux (off-label)
Rabbit & Small Mammals
  • Gastric ulcers (off-label)
  • Gastrointestinal stasis (adjunct)
Avian & Poultry
  • Gastric ulcers (off-label)
  • Regurgitation due to gastric hyperacidity (off-label)
Exotic & Other Species
  • Gastric ulcers in ferrets (off-label)
  • Gastroesophageal reflux in reptiles (off-label)

Pharmacology & Mechanism of Action

Drug Class: H2 receptor antagonist | Pharmacological Group: Gastrointestinal agent

Mechanism of Action: Cimetidine is a competitive, reversible antagonist of histamine at the H2 receptors on gastric parietal cells. By blocking histamine-induced acid secretion, it reduces basal and stimulated gastric acid production, including that stimulated by food, pentagastrin, and insulin. It also reduces pepsin output and gastric juice volume.

Pharmacodynamics: Cimetidine inhibits both basal and stimulated gastric acid secretion. It reduces total acid output and decreases the volume of gastric secretion. It also reduces pepsin secretion. The effect is dose-dependent and lasts for several hours. It does not affect gastric emptying or lower esophageal sphincter pressure significantly.

⚑ Pharmacokinetics Summary

Absorption: Cimetidine is well absorbed after oral administration, with peak plasma concentrations occurring 1-2 hours after dosing. Bioavailability is approximately 60-70% due to first-pass metabolism. Food may delay absorption but does not significantly reduce total absorption.
Distribution: Cimetidine is widely distributed throughout the body, including into cerebrospinal fluid, placenta, and milk. It crosses the blood-brain barrier and can cause CNS effects. Protein binding is approximately 20%.
Metabolism: Cimetidine is metabolized in the liver primarily to cimetidine sulfoxide and 5-hydroxymethylcimetidine. It also inhibits cytochrome P450 enzymes, particularly CYP1A2, CYP2C9, CYP2D6, and CYP3A4, leading to drug interactions.
Excretion: Cimetidine is excreted primarily in the urine, both as unchanged drug and metabolites. Renal clearance is significant, and dosage adjustment is needed in renal impairment. A small amount is excreted in bile and feces.
Half-Life: The elimination half-life is approximately 2-3 hours in dogs, 1.5-2 hours in cats, and 1-2 hours in horses. In renal impairment, half-life may be prolonged.
Bioavailability: Oral bioavailability is approximately 60-70% in dogs and cats, with some variation among species.
Protein Binding: Approximately 20% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 100 mg, 200 mg, 300 mg, 400 mg, 800 mg (PO)
Oral Liquid 300 mg/5 mL (PO)
Injectable Solution 150 mg/mL (IV, IM)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to cimetidine or other H2 antagonists
  • Severe renal impairment (requires dose adjustment)
  • Use in animals with known CNS disorders (may exacerbate)
  • Concurrent use with drugs that require gastric acid for absorption (e.g., ketoconazole, itraconazole, atazanavir) may reduce their efficacy
Warnings & Clinical Precautions:
  • Use with caution in animals with hepatic or renal impairment; dose adjustment may be necessary.
  • May cause CNS signs (confusion, agitation, seizures) especially in cats and elderly animals.
  • In food animals, observe withdrawal times; extra-label use requires veterinary oversight.
  • Cimetidine can inhibit cytochrome P450 enzymes, leading to increased plasma levels of many drugs; monitor for toxicity.
  • Long-term use may lead to vitamin B12 deficiency due to reduced acid secretion.
  • In horses, oral cimetidine may be less effective than omeprazole for gastric ulcers; consider alternative therapy.

Adverse Effects & Reactions

Common:

  • Diarrhea
  • Vomiting
  • Anorexia
  • Lethargy
  • CNS depression (especially in cats)

Serious / Severe:

  • Arrhythmias (with rapid IV administration)
  • Seizures
  • Bone marrow suppression (rare)
  • Hepatotoxicity (rare)
  • Interstitial nephritis (rare)

Rare:

  • Gynecomastia (in males with prolonged use)
  • Hyperprolactinemia
  • Bradycardia
  • Hypotension
  • Confusion

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Ketoconazole, Itraconazole Cimetidine reduces gastric acidity, decreasing absorption of these azole antifungals. Moderate
Warfarin Cimetidine inhibits CYP2C9, increasing warfarin levels and risk of bleeding. High
Theophylline Cimetidine inhibits CYP1A2, increasing theophylline levels and risk of toxicity. High
Phenytoin Cimetidine inhibits CYP2C9, increasing phenytoin levels and risk of toxicity. High
Lidocaine Cimetidine reduces hepatic blood flow and inhibits CYP1A2, increasing lidocaine levels. Moderate
Beta-blockers (e.g., propranolol) Cimetidine increases bioavailability of beta-blockers by reducing hepatic metabolism. Moderate
Calcium channel blockers (e.g., diltiazem, nifedipine) Cimetidine inhibits CYP3A4, increasing levels of these drugs. Moderate
Benzodiazepines (e.g., diazepam, midazolam) Cimetidine inhibits CYP3A4, increasing sedative effects. Moderate
Tricyclic antidepressants (e.g., amitriptyline) Cimetidine inhibits metabolism, increasing levels and risk of toxicity. Moderate
Sucralfate Sucralfate may bind to cimetidine, reducing its absorption; separate administration by at least 2 hours. Mild
Antacids Antacids may reduce absorption of cimetidine; separate administration by at least 1 hour. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • CNS depression
  • Confusion
  • Seizures
  • Respiratory depression
  • Arrhythmias
  • Hypotension

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide respiratory support, anticonvulsants (e.g., diazepam) for seizures, and cardiovascular support (fluids, pressors) as needed. Monitor ECG and vital signs. There is no specific antidote; cimetidine is dialyzable, but hemodialysis is rarely needed.

Food Animal Withdrawal Times

πŸ₯© Meat: 0 daysπŸ₯› Milk: 0 daysπŸ₯š Eggs: 0 days

Cimetidine is not approved for food animals in the US. Extra-label use requires extended withdrawal times; consult FARAD (Food Animal Residue Avoidance Databank) for specific recommendations. In general, a withdrawal time of at least 7 days for meat and 72 hours for milk is suggested, but official guidance should be followed.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25Β°C, 68-77Β°F). Protect from moisture.

Handling & Special Conditions: Keep container tightly closed. Injectable solution should be stored at room temperature and protected from freezing.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use. Veterinary use is extra-label.

Extra-Label (Off-Label) Use: Cimetidine is not FDA-approved for veterinary species, but it is commonly used in an extra-label manner under the Animal Medicinal Drug Use Clarification Act (AMDUCA). Extra-label use in food animals requires a valid veterinary-client-patient relationship and must not result in violative residues. Withdrawal times must be extended based on FARAD recommendations.

Clinical Pearls & Practice Notes

πŸ’‘ Clinical Insights: Cimetidine is a histamine H2 receptor antagonist used to reduce gastric acid secretion in various animal species. It is effective for treating gastric ulcers, esophagitis, and gastroesophageal reflux. However, in horses, omeprazole (a proton pump inhibitor) is often preferred due to superior efficacy. Cimetidine has a relatively short duration of action, requiring frequent dosing (q8h). It is a potent inhibitor of cytochrome P450 enzymes, leading to numerous drug interactions; therefore, it should be used with caution in polypharmacy cases. In cats, CNS side effects are more common, and dosing should be conservative. For food animals, extra-label use requires careful attention to withdrawal times. Overall, cimetidine is a cost-effective option for acid suppression, but newer agents like famotidine or omeprazole may offer advantages in terms of potency and dosing frequency.

References & Literature

  • πŸ“š Plumb's Veterinary Drug Handbook
  • πŸ“š Papich Veterinary Pharmacology and Therapeutics
  • πŸ“š Compendium of Veterinary Products (CVP)