Alloxate 5 mg/mL Solution for Injection for Dogs

Company: Pivetal

Package Insert for Dogs

Approved by FDA under ANADA # 200-491

(meloxicam)

5 mg/mL Solution for Injection

Non-steroidal anti-inflammatory drug for use in dogs and cats only.

Alloxate 5 mg/mL Solution for Injection for Dogs Caution

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Description

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class. Each mL of this sterile product for injection contains meloxicam 5.0 mg, alcohol 15%, glycofurol 10%, poloxamer 188 5%, sodium chloride 0.6%, glycine 0.5% and meglumine 0.3%, in water for injection, pH adjusted with sodium hydroxide and hydrochloric acid.

Alloxate 5 mg/mL Solution for Injection for Dogs Indications

Dogs: Alloxate™ (meloxicam) 5 mg/mL Solution for Injection is indicated in dogs for the control of pain and inflammation associated with osteoarthritis.

Dosage and Administration

Carefully consider the potential benefits and risk of Alloxate and other treatment options before deciding to use Alloxate. Use the lowest effective dose for the shortest duration consistent with individual response.

Dogs: Alloxate 5 mg/mL Solution for Injection should be administered initially as a single dose at 0.09 mg/lb (0.2 mg/kg) body weight intravenously (IV) or subcutaneously (SQ), followed, after 24 hours, by Meloxicam Oral Suspension at the daily dose of 0.045 mg/lb (0.1 mg/kg) body weight, either mixed with food or placed directly in the mouth.

Contraindications

Dogs with known hypersensitivity to meloxicam should not receive Alloxate 5 mg/mL Solution for Injection.

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 IV or SQ injectable use in dogs. All dogs should undergo a thorough history and physical examination before administering any NSAID. Appropriate laboratory testing to establish hematological and serum biochemical baseline data is recommended prior to, and periodically during use of any NSAID in dogs.

Owner should be advised to observe their dogs for signs of potential drug toxicity.

Precautions

The safe use of Alloxate 5 mg/mL Solution for Injection in dogs younger than 6 months of age, dogs used for breeding, or in pregnant or lactating bitches 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. Safety has not been established for intramuscular (IM) administration in dogs. When administering Alloxate 5 mg/mL Solution for Injection, use a syringe of appropriate size to ensure precise dosing. 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 the administration of the total daily dose of meloxicam oral suspension, a non-NSAID or noncorticosteroid 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 Alloxate 5 mg/mL Solution for Injection 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 Alloxate 5 mg/mL Solution for Injection has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy. The effect of cyclo-oxygenase inhibition and the potential for thromboembolic occurrence or a hypercoagulable state has not been studied.

Adverse Reactions

Dogs: A field study involving 224 dogs was conducted. Based on the results of this study, 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 study. Dogs may have experienced more than one episode of the adverse reaction during the study.

In foreign suspected adverse drug reaction (SADR) reporting, 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).

Post-approval Experience (rev. 2009)

The following adverse reactions are based on post-approval adverse drug event reporting. The categories are listed in decreasing order of frequency by body system:

Gastrointestinal: vomiting, diarrhea, melena, gastrointestinal ulceration

Urinary: azotemia, elevated creatinine, renal failure

Neurological:/Behavioral: lethargy, depression

Hepatic: elevated liver enzymes

Dermatologic: pruritus

Death has been reported as an outcome of the adverse events listed above. Acute renal failure and death have been associated with the use of meloxicam in cats.

To report suspected adverse drug events, for technical assistance or to obtain a copy of the SDS, call 1-866-591-5777.

For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth.

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 be advised when their pet has received a meloxicam injection. Dog owners should contact their veterinarian immediately if possible adverse reactions are observed, and dog owners should be advised to discontinue Alloxate therapy.

Clinical Pharmacology

Meloxicam has nearly 100% bioavailability when administered orally or after subcutaneous injection in dogs. The terminal elimination half-life after a single dose is estimated to be approximately 24 hrs (+/-10%) in dogs regardless of route of administration. 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 of 0.734 mcg/mL can be expected to occur within 2.5 hours following a 0.2 mg/kg subcutaneous injection in dogs. Based upon intravenous administration in Beagle dogs, the meloxicam volume of distribution in dogs (Vdλ) is approximately 0.32 L/kg and the total systemic clearance is 0.01 L/hr/kg. The drug is 97% bound to canine plasma proteins.

Effectiveness

Dogs: The effectiveness of meloxicam injection was demonstrated in a field study involving a total of 224 dogs representing various breeds, all diagnosed with osteoarthritis. This placebo-controlled, masked study was conducted for 14 days. Dogs received a subcutaneous injection of 0.2 mg/kg meloxicam injection on day 1. The dogs were maintained on 0.1 mg/kg oral meloxicam from days 2 through 14. Variables evaluated by veterinarians included lameness, weight-bearing, pain on palpation, and overall improvement. Variables assessed by owners included mobility, ability to rise, limping, and overall improvement.

In this field study, dogs showed clinical improvement with statistical significance after 14 days of meloxicam treatment for all variables.

Animal Safety:

Dogs: 3 Day Target Animal Safety Study - In a three day safety study, meloxicam injection was administered intravenously to Beagle dogs at 1, 3, and 5 times the recommended dose (0.2, 0.6 and 1.0 mg/kg) for three consecutive days. Vomiting occurred in 1 of 6 dogs in the 5X group. Fecal occult blood was detected in 3 of 6 dogs in the 5X group. No clinically significant hematologic changes were seen, but serum chemistry changes were observed. Serum alkaline phosphatase (ALP) was significantly increased in one 1X dog and two of the 5X dogs. One dog in the 5X group had a steadily increasing GGT over 4 days, although the values remained within the reference range. Decreases in total protein and albumin occurred in 2 of 6 dogs in the 3X group and 3 of 6 dogs in the 5X group. Increases in blood urea nitrogen (BUN) occurred in 3 of 6 dogs in the 1X group, 2 of 6 dogs in the 3X group and 2 of 6 dogs in the 5X group. Increased creatinine occurred in 2 dogs in the 5X group. Increased urine protein excretion was noted in 2 of 6 dogs in the control group, 2 of 6 dogs in the 1X group, 2 of 6 dogs in the 3X group, and 5 of 6 dogs in the 5X group. Two dogs in the 5X group developed acute renal failure by Day 4. Bicarbonate levels were at or above normal levels in 1 of the 3X dogs and 2 of the 5X dogs. Histological examination revealed gastrointestinal lesions ranging from superficial mucosal hemorrhages and congestion to erosions. Mesenteric lymphadenopathy was identified in 2 of 6 dogs in the 1X group, 4 of 6 dogs in the 3X group, and 5 of 6 dogs in the 5X group. Renal changes ranged from dilated medullary and cortical tubules and inflammation of the interstitium, to necrosis of the tip of the papilla in 2 of 6 dogs in the 1X group, 2 of 6 dogs in the 3X group, and 4 of 6 dogs in the 5X group.

Injection Site Tolerance - Meloxicam injection was administered once subcutaneously to Beagle dogs at the recommended dose of 0.2 mg/kg and was well-tolerated by the dogs. Pain upon injection was observed in one of eight dogs treated with meloxicam. No pain or inflammation was observed post injection. Long term use of meloxicam injection in dogs has not been evaluated.

Effect on Buccal Mucosal Bleeding Time (BMBT) - Meloxicam injection (0.2 mg/kg) and placebo (0.4 mL/kg) were administered as single intravenous injections to 8 female and 16 male Beagle dogs. There was no statistically significant difference (p>0.05) in the average BMBT between the two groups.

Storage Information:

Store at controlled room temperature, 68-77°F (20-25°C). Use within 180 days of first puncture and puncture a maximum of 51 times.

How Supplied

Alloxate 5 mg/mL Solution for Injection: 10 mL and 20 mL vial

Made in the UK.

Manufactured For: Aspen Veterinary Resources^®, LTD., Liberty, MO 64068

www.pivetalvet.com

Alloxate™ is a trademark of Aspen Veterinary Resources^®, LTD.

Pivetal™ is a trademark, or registered trademark, of Aspen Veterinary Resources^®, LTD. All rights reserved.

08/19 653974I02

CPN: 2028021.0