Mesalamine — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	10-20 mg/kg	q8h (every 8 hours)	Duration: Long-term; often 4-6 weeks for initial response, then taper to lowest effective dose Notes: Use with food to reduce GI upset. For granulomatous colitis in Boxers, combine with enrofloxacin (5-10 mg/kg q24h) for 8-10 weeks.
Cat	PO	10-20 mg/kg	q12h (every 12 hours)	Duration: Long-term; reassess after 4-6 weeks Notes: Cats may be more sensitive to adverse effects; monitor renal function. Use with caution in cats with kidney disease.
Dog	Rectal (enema)	1-4 g per enema	q24h (once daily) at bedtime	Duration: As directed for colitis Notes: Use commercially available enema preparations (e.g., Rowasa). Administer after bowel movement.
Cat	Rectal (suppository)	250 mg per suppository	q24h (once daily)	Duration: As directed for colitis Notes: May be difficult to administer; consider oral therapy if not tolerated.

Clinical Indications & Species Uses

General Indications

Treatment of inflammatory bowel disease (IBD) in dogs and cats, particularly when colitis is a component

Dog (Canine)

Inflammatory bowel disease (IBD)
Lymphocytic-plasmacytic colitis
Histiocytic ulcerative colitis
Granulomatous colitis (in Boxers, often in combination with antibiotics)

Cat (Feline)

Inflammatory bowel disease (IBD)
Lymphocytic-plasmacytic enteritis/colitis

Pharmacology & Mechanism of Action

Drug Class: 5-Aminosalicylate | Pharmacological Group: Anti-inflammatory (GI)

Mechanism of Action: Mesalamine (5-aminosalicylic acid, 5-ASA) is the therapeutically active moiety of sulfasalazine. It acts locally on the intestinal mucosa to reduce inflammation. The exact mechanism is not fully understood, but it is thought to inhibit cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene synthesis. It also scavenges reactive oxygen species, inhibits cytokine production (e.g., IL-1, TNF-α), and modulates nuclear factor kappa B (NF-κB) activity, thereby decreasing mucosal inflammation and promoting healing in inflammatory bowel disease (IBD).

Pharmacodynamics: Mesalamine exerts its anti-inflammatory effects primarily in the colon and distal small intestine. It reduces mucosal inflammation, decreases neutrophil chemotaxis, and inhibits the production of pro-inflammatory mediators. It also has antioxidant properties. The drug is poorly absorbed systemically, with most of the dose remaining in the GI tract, which maximizes local therapeutic effect while minimizing systemic side effects. Clinical improvement in IBD is typically seen within 3-7 days of therapy.

⚡ Pharmacokinetics Summary

Absorption: Mesalamine is poorly absorbed from the small intestine; absorption is variable and depends on the formulation. Oral formulations (e.g., delayed-release, extended-release) are designed to deliver the drug to the distal small intestine and colon. Rectal formulations (suppositories, enemas) provide local delivery. In dogs, oral bioavailability is approximately 20-30%.

Distribution: The drug is distributed mainly in the GI tract, with minimal systemic distribution. The volume of distribution is low. It crosses the placenta and is excreted in milk, but systemic levels are low.

Metabolism: Mesalamine is metabolized in the intestinal mucosa and liver to N-acetyl-5-aminosalicylic acid (N-acetyl-5-ASA) via N-acetyltransferase. This metabolite is inactive.

Excretion: The drug and its metabolite are excreted primarily in the feces (unabsorbed portion) and urine (absorbed portion). In dogs, approximately 70-80% of the dose is recovered in feces, and 20-30% in urine.

Half-Life: The plasma half-life is short (0.5-2 hours in dogs and cats), but the local effect in the GI tract is prolonged due to high luminal concentrations.

Bioavailability: Oral bioavailability is low (20-30%) due to poor absorption and first-pass metabolism. Rectal administration results in lower systemic absorption but higher local concentrations.

Protein Binding: Mesalamine is approximately 40-50% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet (delayed-release) 400 mg, 800 mg, 1200 mg (PO)

Oral Capsule (extended-release) 250 mg, 375 mg, 500 mg (PO)

Oral Suspension (reconstituted) 1.2 g/60 mL (after reconstitution) (PO)

Rectal Suppository 500 mg, 1000 mg (Rectal)

Rectal Enema (suspension) 4 g/60 mL (Rectal)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to mesalamine, salicylates, or any component of the formulation
Known severe renal impairment (use with caution; may worsen renal function)
History of hypersensitivity to sulfasalazine (cross-reactivity possible)

Warnings & Clinical Precautions:

Use with caution in patients with renal disease; monitor renal function (BUN, creatinine, urinalysis) periodically.
Use with caution in patients with hepatic impairment.
May cause blood dyscrasias; monitor CBC in long-term therapy.
In cats, use with caution due to potential for renal toxicity and GI upset.
Do not crush or chew delayed-release tablets; administer whole.
If using enema, instruct owner on proper administration technique.
Discontinue if signs of hypersensitivity (rash, fever, eosinophilia) occur.

Adverse Effects & Reactions

Common:

Vomiting
Diarrhea
Anorexia
Nausea
Flatulence
Abdominal pain

Serious / Severe:

Nephrotoxicity (interstitial nephritis)
Hepatotoxicity
Blood dyscrasias (leukopenia, thrombocytopenia, agranulocytosis)
Exacerbation of colitis (rare)
Hypersensitivity reactions (dermatitis, fever, eosinophilia)

Rare:

Pancreatitis
Pericarditis
Pulmonary fibrosis
Neurotoxicity (seizures, peripheral neuropathy)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Azathioprine or 6-Mercaptopurine	Mesalamine may inhibit TPMT (thiopurine methyltransferase), increasing the risk of myelosuppression from azathioprine/6-MP.	High
Warfarin and other anticoagulants	Mesalamine may enhance the anticoagulant effect, increasing bleeding risk.	Moderate
NSAIDs (e.g., carprofen, meloxicam)	Additive nephrotoxicity and GI irritation.	Moderate
Corticosteroids	May increase risk of GI ulceration; monitor for signs of bleeding.	Moderate
Digoxin	Mesalamine may reduce the absorption of digoxin.	Mild

Overdose & Toxicity Management

Signs of Toxicity:

Vomiting
Diarrhea
Abdominal pain
Lethargy
Tinnitus (in humans; may occur in animals)
Hyperventilation
Renal failure (with massive overdose)

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce vomiting if recent ingestion and the animal is conscious. Administer activated charcoal to reduce absorption. Provide IV fluids to maintain hydration and renal perfusion. Monitor renal function, electrolytes, and acid-base status. In severe cases, consider hemodialysis (though rarely needed).

Food Animal Withdrawal Times

Not approved for use in food-producing animals. Withdrawal times are not established. Do not use in animals intended for food.

Storage, Handling & Regulatory Information

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

Handling & Special Conditions: Keep container tightly closed. For oral suspension, reconstitute with water and use within 2 weeks; store reconstituted suspension at room temperature or refrigerate (do not freeze).

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use (e.g., Asacol, Pentasa, Rowasa).

Extra-Label (Off-Label) Use: In the US, mesalamine is not FDA-approved for veterinary use; use in animals is extra-label. Must follow AMDUCA regulations: require a valid veterinarian-client-patient relationship, and for food animals, extended withdrawal times must be considered. Not for use in food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Mesalamine is a valuable drug for managing inflammatory bowel disease (IBD) in dogs and cats, particularly when colitis is a major component. It is generally well-tolerated, but renal toxicity is a concern, especially in cats and animals with pre-existing renal disease. Baseline and periodic monitoring of renal function (BUN, creatinine, urinalysis) and CBC are recommended. The drug is most effective when used as part of a comprehensive treatment plan that may include dietary modification, probiotics, and immunosuppressive agents (e.g., corticosteroids) in severe cases. In dogs with granulomatous colitis (Boxers), combination with enrofloxacin is often necessary. Owners should be educated on proper administration, especially for rectal formulations. Due to the lack of veterinary-approved formulations, compounding may be required; ensure stability and accurate dosing. Avoid use in food animals due to lack of withdrawal data.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)