Clinical Pharmacology: Meloxicam has nearly 100% bioavailability when administered orally with food. The terminal elimination half life after a single dose is estimated to be approximately 24 hrs (+/-30%) regardless of route of administration. There is no evidence of statistically significant gender differences in drug pharmacokinetics. Drug bioavailability, volume of distribution, and total systemic clearance remain constant up to 5 times the recommended dose for use in dogs. However, there is some evidence of enhanced drug accumulation and terminal elimination half-life prolongation when dogs are dosed for 45 days or longer.

Peak drug concentrations can be expected to occur within about 7.5 hrs after oral administration. Corresponding peak concentration is approximately 0.464 mcg/mL following a 0.2 mg/kg oral dose. The drug is 97% bound to canine plasma proteins.

Indications: Metacam^® Oral Suspension is indicated for the control of pain and inflammation associated with osteoarthritis in dogs.

Dosage and Administration: Always provide client information sheet with prescription. Carefully consider the potential benefits and risk of Metacam and other treatment options before deciding to use Metacam. Use the lowest effective dose for the shortest duration consistent with individual response. Metacam^® Oral Suspension should be administered initially at 0.09 mg/lb (0.2 mg/kg) body weight only on the first day of treatment. For all treatments after day 1, Metacam^® Oral Suspension should be administered once daily at a dose of 0.045 mg/lb (0.1 mg/kg). The syringe is calibrated to deliver the daily maintenance dose in pounds.

Directions for Administration:

Dogs under 10 pounds (4.5 kg)

Shake well before use, then remove cap. Particular care should be given with regard to the accuracy of dosing. To prevent accidental overdosing of small dogs, administer drops on food only, never directly into the mouth. Carefully measure suspension onto food to assure that the correct dose is given before presentation of the food to the dog. The syringe provided with the meloxicam concentration of 0.5 mg/mL cannot be used to measure doses for dogs weighing less than 1 lb (0.45 kg), and the syringe provided with the meloxicam concentration of 1.5 mg/mL cannot be used to measure doses for dogs weighing less than 5 lbs (2.3 kg).

Metacam^® 0.5 mg/mL Oral Suspension

For dogs less than 1 lb (0.45 kg), Metacam^® Oral Suspension can be given using the dropper bottle: two drops for each pound of body weight for the 0.5 mg/mL concentration (five drops for each kilogram of body weight), dropped directly onto the food.

For dogs between 1-10 pounds, Metacam^® Oral Suspension can be given by drops or by using the measuring syringe provided in the package (see dosing procedure below). The syringe fits on to the bottle and has a scale beginning a

+t 1 lb, designed to deliver the daily maintenance dose (0.05 mg/lb or 0.1 mg/kg). When using the syringe, the dog's weight should be rounded down to the nearest 1 pound increment. Replace and tighten cap after use.

Metacam^® 1.5 mg/mL Oral Suspension

For dogs less than 5 lbs (2.3 kg), Metacam^® Oral Suspension can be given using the dropper bottle: one drop for each pound of body weight for the 1.5 mg/mL concentration (two drops for each kilogram of body weight), dropped directly onto the food.

For dogs between 5-10 pounds, Metacam^® Oral Suspension can be given by drops or by using the measuring syringe provided in the package (see dosing procedure below). The syringe fits on to the bottle and has a scale beginning at 5 lbs, designed to deliver the daily maintenance dose (0.05 mg/lb or 0.1 mg/kg). When using the syringe, the dog's weight should be rounded down to the nearest 5 pound increment. Replace and tighten cap after use.

Dogs over 10 pounds (4.5 kg)

Shake well before use then remove cap. Metacam^® Oral Suspension may be either mixed with food or placed directly into the mouth. Particular care should be given with regard to the accuracy of dosing. Metacam^® Oral Suspension can be given using the measuring syringe provided in the package (see dosing procedure below). The syringe fits on to the bottle and has a scale in pounds designed to deliver the daily maintenance dose (0.05 mg/lb or 0.1 mg/kg). When using the syringe, the dog's weight should be rounded down to the nearest 1 pound increment for Metacam^® 0.5 mg/mL Oral Suspension, or the nearest 5 pound increment for Metacam^® 1.5 mg/mL Oral Suspension. Alternatively, Metacam^® Oral Suspension can be given using the dropper bottle: two drops for each pound of body weight for the 0.5 mg/mL concentration (five drops for each kilogram of body weight), or one drop for each pound of body weight for the 1.5 mg/mL concentration (two drops for each kilogram of body weight). Replace and tighten cap after use.

1. Shake bottle well. Push down and unscrew bottle top. Attach the dosing syringe to the bottle by gently pushing the end onto the top of the bottle.

2. Turn the bottle/syringe upside down. Pull the plunger out until the black line on the plunger corresponds to the dog's body weight in pounds.

3. Turn the bottle right way up and with a twisting movement separate the dosing syringe from the bottle.

4. Push the plunger to empty the contents of the syringe.

Contraindications: Dogs with known hypersensitivity to meloxicam should not receive Metacam^® Oral Suspension. Do not use in cats.

Warnings: Not for use in humans. Keep this and all medications out of reach of children. Consult a physician in case of accidental ingestion by humans. For oral use in dogs only.

As with any NSAID all dogs should undergo a thorough history and physical examination before the initiation of NSAID therapy. Appropriate laboratory testing to establish hematological and serum biochemical baseline data is recommended prior to and periodically during administration. Owner should be advised to observe their dogs for signs of potential drug toxicity and be given a client information sheet about Metacam.

Precautions: The safe use of Metacam^® Oral Suspension in dogs younger than 6 months of age, dogs used for breeding, or in pregnant or lactating dogs has not been evaluated. Meloxicam is not recommended for use in dogs with bleeding disorders, as safety has not been established in dogs with these disorders.

As a class, cyclo-oxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal and hepatic toxicity. Sensitivity to drug-associated adverse events varies with the individual patient. Dogs that have experienced adverse reactions from one NSAID may experience adverse reactions from another NSAID. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with existing renal, cardiovascular, and/or hepatic dysfunction. Concurrent administration of potentially nephrotoxic drugs should be carefully approached. NSAIDs may inhibit the prostaglandins that maintain normal homeostatic function. Such anti-prostaglandin effects may result in clinically significant disease in patients with underlying or pre-existing disease that has not been previously diagnosed. Since NSAIDs possess the potential to induce gastrointestinal ulcerations and/or perforations, concomitant use with other anti-inflammatory drugs, such as NSAIDs or corticosteroids, should be avoided. If additional pain medication is needed after administration of the total daily dose of Metacam Oral Suspension, a non-NSAID or non-corticosteroid class of analgesia should be considered. The use of another NSAID is not recommended. Consider appropriate washout times when switching from corticosteroid use or from one NSAID to another in dogs. The use of concomitantly protein-bound drugs with Metacam^® Oral Suspension has not been studied in dogs. Commonly used protein-bound drugs include cardiac, anticonvulsant and behavioral medications. The influence of concomitant drugs that may inhibit metabolism of Metacam^® Oral Suspension has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy.

Adverse Reactions: Field safety was evaluated in 306 dogs. Based on the results of two studies, GI abnormalities (vomiting, soft stools, diarrhea, and inappetance) were the most common adverse reactions associated with the administration of meloxicam. The following table lists adverse reactions and the numbers of dogs that experienced them during the studies. Dogs may have experienced more than one episode of the adverse reaction during the study.

Adverse Reactions Observed During Two Field Studies
Clinical Observation	Meloxicam (n=157)	Placebo (n=149)
Vomiting	40	23
Diarrhea/Soft Stool	19	11
Bloody Stool	1	0
Inappetance	5	1
Bleeding gums after dental procedure	1	0
Lethargy/Swollen Carpus	1	0
Epiphora	1	0

In foreign suspected adverse drug reaction (SADR) reporting over a 9 year period, incidences of adverse reactions related to meloxicam administration included: auto-immune hemolytic anemia (1 dog), thrombocytopenia (1 dog), polyarthritis (1 dog), nursing puppy lethargy (1 dog), and pyoderma (1 dog).

Information For Dog Owners: Meloxicam, like other NSAIDs, is not free from adverse reactions. Owners should be advised of the potential for adverse reactions and be informed of the clinical signs associated with NSAID intolerance. Adverse reactions may include vomiting, diarrhea, lethargy, decreased appetite and behavioral changes. Dog owners should contact their veterinarian immediately if possible adverse reactions are observed, and dog owners should be advised to discontinue Metacam therapy.

Post-Approval Experience: The following adverse reactions are based on voluntary post-approval reporting. The categories are listed in decreasing order of frequency by body system.

Gastrointestinal: vomiting, anorexia, diarrhea, melena, gastrointestinal ulceration

Urinary: azotemia, elevated creatinine, renal failure

Neurological/Behavioral/Special Sense: lethargy, depression

Hepatic: elevated liver enzymes

Dermatological/Immunological: pruritus

In rare situations, death has been reported as an outcome of the adverse events listed above. Renal failure has been reported as an outcome of repeated oral dosing of cats.

Effectiveness: Proven safe and effective in millions of dogs for over 14 years. The effectiveness of meloxicam was demonstrated in two field studies involving a total of 277 dogs representing various breeds, between six months and sixteen years of age, all diagnosed with osteoarthritis. Both of the placebo-controlled, masked studies were conducted for 14 days. All dogs received 0.2 mg/kg on day 1. All dogs were maintained on 0.1 mg/kg oral meloxicam from days 2 through 14 of both studies. Parameters evaluated by veterinarians included lameness, weight-bearing, pain on palpation, and overall improvement. Parameters assessed by owners included mobility, ability to rise, limping, and overall improvement.

In the first field study (n=109), dogs showed clinical improvement with statistical significance after 14 days of meloxicam treatment for all parameters. In the second field study (n=48), dogs receiving meloxicam showed a clinical improvement after 14 days of therapy for all parameters; however, statistical significance was demonstrated only for the overall investigator evaluation on day 7, and for the owner evaluation on day 14.

Palatability: Dogs love the sweet honey flavor. Metacam^® Oral Suspension was accepted by 100% of the dogs when veterinarians administered the initial dose into the mouth. Metacam^® Oral Suspension was accepted by 90% of the dogs (123/136) when administered by owners. Problems associated with administration included refusal of food, resistance to swallowing and salivation.