PIROXICAM

Chemistry - An oxicam derivative non-steroidal antiinflammatory agent, piroxicam occurs as awhite, crystalline solid. It is sparingly soluble in water. Piroxicam is structurally not related to othernon-steroidal antiinflammatory agents.

Storage, Stability, Compatibility

Capsules should be stored at temperatures less than 30°C intight, light-resistant containers. When stored as recommended, capsules have an expiration date of36 months after manufacture.

Pharmacology - PIROXICAM

Like other non-steroidal antiinflammatory agents, piroxicam has antiinflammatory, analgesic and antipyretic activity. The drug's antiinflammatory activity is thought to beprimarily due to its inhibition of prostaglandin synthesis, but additional mechanisms (e.g., superoxide formation inhibition) may be important. As with other NSAIDs, piroxicam can affect renalfunction, cause GI mucosal damage, and inhibit platelet aggregation.

Uses, Indications

In dogs, piroxicam may be beneficial in reducing the pain and inflammationassociated with degenerative joint disease. It also has been used in dogs as adjunctive treatment ofbladder transitional cell carcinoma.

Pharmacokinetics - PIROXICAM

After oral administration, piroxicam is well absorbed from the gut. While thepresence of food will decrease the rate of absorption, it will not decrease the amount absorbed. It isnot believed that antacids significantly affect absorption.
Piroxicam is highly bound to plasma proteins. In humans, synovial levels are about 40% of thosefound in the plasma. Maternal milk concentrations are only about 1% of plasma levels.
In humans, piroxicam has a very long plasma half-life (about 50 hours). The drug is principallyexcreted as metabolites in the urine after hepatic biotransformation.

Contraindications, Precautions, Reproductive Safety

Piroxicam is contraindicated in patientshypersensitive to it or who are severely allergic to aspirin or other NSAIDs. It should be used onlywhen its potential benefits outweigh the risks in patients with active, or a history of GI ulcer diseaseor bleeding disorders. Because peripheral edema has been noted in some human patients, it shouldbe used with caution in patients with severely compromised cardiac function.
Animal studies have not demonstrated any teratogenic effects associated with piroxicam. The drugis excreted into milk in very low concentrations (about 1% found in maternal plasma).

Adverse Effects, Warnings

Like other NSAIDs used in dogs, piroxicam has the potential forcausing significant GI ulceration and bleeding. The therapeutic window for the drug is very narrowin dogs as doses as low as 1 mg/kg given daily have caused significant GI ulceration, renal papillarynecrosis, and peritonitis. Other adverse effects reported in humans and potentially possible in dogsinclude CNS effects (headache, dizziness, etc.), otic effects (tinnitus), elevations in hepatic functiontests, pruritus and rash, and peripheral edema.
Overdosage, Acute Toxicity - There is limited information available, but dogs may be moresensitive to the drugs ulcerative effects than are humans. Patients ingesting significant overdosesshould be monitored carefully and gut removal techniques employed when warranted. Treatment issupportive.

Drug Interactions

Because piroxicam is highly bound to plasma proteins, it can displace or bedisplaced by other highly protein bound drugs, including warfarin, phenylbutazone, etc.
Because piroxicam may inhibit platelet aggregation and also cause gastrointestinal ulceration, when used with other drugs that alter hemostasis (e.g., heparin, warfarin, etc.) and/or cause gastrointestinal erosion (e.g., aspirin, flunixin, phenylbutazone, corticosteroids, etc.), increasedlikelihood of bleeding or ulceration may occur.
NSAIDs (including piroxicam ) may potentially significantly reduce the excretion ofmethotrexate and cause toxicity.
Laboratory Considerations - Piroxicam may cause falsely elevated blood glucose values whenusing the glucose oxidase and peroxidase method using ABTS as a chromogen.