Olsalazine

Overview

Olsalazine (Dipentum®) is a locally acting anti-inflammatory drug used in dogs for the management of chronic colitis, particularly in patients that cannot tolerate the adverse effects associated with sulfasalazine. Veterinary use is based primarily on empirical and human experience; no well-controlled clinical studies or efficacy trials document effectiveness in animals.

Olsalazine delivers approximately twice the amount of mesalamine (5-aminosalicylic acid; 5-ASA) to the colon compared with sulfasalazine. Because both drugs act by delivering 5-ASA to the large intestine, alternative treatment options may be more appropriate in dogs that have failed to respond to sulfasalazine therapy.

Mechanism of Action (MOA): Olsalazine is cleaved by colonic bacteria in the large intestine into two molecules of mesalamine (5-ASA). Although the exact mechanism is not fully understood, mesalamine exerts local anti-inflammatory effects within the colon, including inhibition of cyclooxygenase and lipoxygenase pathways. Olsalazine may also inhibit water and electrolyte absorption in the small intestine, which is thought to contribute to its tendency to cause watery diarrhea.

Indications

Olsalazine is used in dogs for the management of chronic colitis, particularly when sulfasalazine cannot be tolerated because of adverse effects.

• Chronic colitis: Used as an alternative 5-ASA prodrug for management of chronic inflammatory colonic disease.
• Sulfasalazine intolerance: May be considered in dogs that develop adverse effects associated with sulfasalazine therapy.

Dosage (Reference)

Dog

Olsalazine is used extra-label in dogs for inflammatory bowel disease and chronic colitis. It is not commonly recommended unless the patient cannot tolerate sulfasalazine.

Warnings & Precautions

Olsalazine is contraindicated in patients hypersensitive to it or to salicylates, and should be used cautiously in animals with renal disease.

• Hypersensitivity: Contraindicated in patients with known or suspected hypersensitivity to olsalazine, to salicylates or to other aminosalicylates.
• Renal disease: Use with caution in animals with renal impairment, as nephritis and renal tubular damage have been reported rarely in human and experimental animal patients.
• Nursing animals: Use cautiously in lactating patients; doses 5 to 20 times the human dose produced growth delays in the pups of lactating rats.
• Pregnancy and reproduction: Olsalazine did not affect fertility in rats, but some fetal abnormalities occurred in high-dose rat studies; use during pregnancy only when the maternal benefits outweigh the potential risks to offspring.
• Nephrolithiasis: Nephrolithiasis has been reported in people receiving mesalamine, the active moiety of olsalazine. Mesalamine-containing stones are radiotransparent and may be undetectable by standard radiography or CT; therefore, negative imaging does not exclude their presence. Ensure adequate fluid intake during treatment. The relevance of this risk to dogs and cats is unknown. 

Drug Interactions

The following interactions have been reported or are theoretical in humans or animals and may be clinically significant in veterinary patients. Additional monitoring may be warranted when used concurrently with the following medications.

• Heparin and low molecular weight heparins (e.g., dalteparin, enoxaparin): Concurrent use may increase the risk of bleeding.
• Mercaptopurine: May increase the risk of myelosuppression when administered together.
• Nonsteroidal anti-inflammatory drugs (NSAIDs): Concurrent use may increase risk for GI bleeding.
• Warfarin: Olsalazine may increase prothrombin times in patients receiving warfarin.
• Azathioprine: Aminosalicylates may increase azathioprine toxicity. In people, mesalamine with azathioprine or 6-mercaptopurine may increase the risk of blood disorders and marrow suppression; if the combination is used, monitor complete blood counts and platelet counts.

Side Effects & Overdose

Side Effects

In humans, transient watery diarrhea is the main reported adverse effect of olsalazine. In some cases, it may be difficult to distinguish this effect from clinical signs associated with the underlying colitis.

• Watery diarrhea: In humans this is the main reported adverse effect; 17% developed diarrhea at some point during therapy, and the effect appears dose-related and transient.
• Keratoconjunctivitis sicca (KCS): Occasionally reported in dogs receiving olsalazine. Its incidence is lower than with sulfasalazine but the risk is not completely eliminated; tell owners to report mucoid ocular discharge, redness or squinting.

Overdose

Overdose in dogs may cause vomiting, diarrhea and decreased motor activity. Treatment is supportive and directed toward management of clinical signs.

• Vomiting: May occur following excessive doses.
• Diarrhea: May occur following an overdose.
• Decreased motor activity: Reduced activity levels may be observed.
• Management: Supportive treatment.
• Overdose consultation: For known or suspected overdose, consult a 24-hour poison service specializing in veterinary cases.
• Safety margin: Doses up to 2 g/kg were not lethal in dogs.

Key Notes

Practical clinical points that may help optimize the use of olsalazine in dogs:

• Limited veterinary experience: Clinical experience with olsalazine in dogs remains relatively limited compared with other treatment options used for chronic colitis.
• High colonic delivery: In humans, approximately 98% of an administered dose reaches the colon intact before bacterial conversion to the active compound.
• Efficient activation in the colon: In humans, about 90% of the drug reaching the colon is converted to mesalamine by colonic bacteria.
• Minimal systemic exposure: In humans, olsalazine is poorly absorbed and absorbed drug is rapidly eliminated; only about 2% of the salicylate from this compound is absorbed systemically.
• Short serum half-life: In humans, the reported serum half-life is approximately 1 hour.
• Monitoring: Monitor clinical efficacy and adverse effects, with a baseline and periodic serum renal chemistry panel (for example BUN and creatinine) and urinalysis; some references state that no specific monitoring is necessary.
• Liver enzymes: Olsalazine may cause increases in ALT and AST concentrations.