Onsior (tablets for dogs) (40 mg) (Canada)

This page contains information on Onsior (tablets for dogs) (40 mg) for veterinary use.
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  • Onsior (tablets for dogs) (40 mg) Indications
  • Warnings and cautions for Onsior (tablets for dogs) (40 mg)
  • Direction and dosage information for Onsior (tablets for dogs) (40 mg)

Onsior (tablets for dogs) (40 mg)

This treatment applies to the following species:
Manufacturer: Novartis

(robenacoxib)

(Robenacoxib tablets for Dogs 5 mg, 10 mg, 20 mg and 40 mg)

Non-Steroidal Anti-Inflammatory

FOR VETERINARY USE ONLY

For use in dogs only.

Description

PrONSIOR™ contain robenacoxib which is a non-steroidal anti-inflammatory drug (NSAID) belonging to the coxib class. The tablets are round, beige to brown in colour and are not scored.

Onsior (tablets for dogs) (40 mg) Indications

PrONSIOR™ (robenacoxib) is indicated for the relief of pain and inflammation associated with osteoarthritis in dogs.

Dosage and Administration

Give orally without food or with a very small quantity of food.

The recommended dosage of ONSIOR is 1 mg/kg body weight with a range 1-2 mg/kg. Administer once per day according to the table below. There is no maximal limit to duration of treatment. Use the lowest effective dose for the shortest duration consistent with the individual response.

Body weight (Kg)

Number of tablets by size

 

5 mg

10 mg

20 mg

40 mg

2.5 to < 5

1 tablet

 

 

 

5 to < 10

 

1 tablet

 

 

10 to < 20

 

 

1 tablet

 

20 to < 40

 

 

 

1 tablet

40 to 80

 

 

 

2 tablets

Contraindications

As with all non-steroidal anti-inflammatory drugs (NSAIDs), administration of this drug is contraindicated in the following circumstances:

• dogs with gastrointestinal ulcers, renal disease, hepatic disorders, hypoproteinemia, dehydration, cardiac disease or coagulation disorders;

• a known hypersensitivity to robenacoxib or its excipients;

• concurrent use of other NSAIDs or corticosteroids;

• do not use in breeding, pregnant or lactating animals because the safety of robenacoxib has not been established.

CAUTIONS:

The safety of ONSIOR has not been established in dogs weighing less than 2.5 kg or under 6 months of age.

All dogs should undergo a thorough history and physical exam before the initiation of NSAID therapy. Appropriate laboratory tests should be conducted to establish hematological and biochemical baseline data before the administration of an NSAID.

When administering NSAIDs for long-term therapy, liver enzymes should be monitored at the start of therapy, e.g. after 2, 4 and 8 weeks. Thereafter it is recommended to continue regular monitoring, e.g. every 3-6 months. Therapy should be discontinued if liver enzyme activities increase markedly or the dog shows clinical signs such as anorexia, apathy or vomiting in combination with elevated liver enzymes.

ONSIOR should be used with caution in dogs with a known hypersensitivity to other NSAIDs.

Pretreatment with other anti-inflammatory medicines may result in additional or increased adverse effects and accordingly a treatment-free period with such substances should be observed. The treatment-free period should take into account the pharmacokinetic properties of the products used previously. Concomitant treatment with drugs which affect renal flow, e.g. anesthetics should be subject to clinical monitoring.

Concurrent administration of potentially nephrotoxic drugs should be avoided as there might be an increase of renal toxicity. Studies to determine the activity of robenacoxib when administered concomitantly with other protein-bound or similarly metabolized drugs have not been conducted. Drug compatibility should be monitored closely in patients requiring additional therapy.

If gastrointestinal or other side effects occur, treatment should be discontinued.

Warnings

KEEP OUT OF REACH OF CHILDREN. In case of accidental ingestion, seek medical advice immediately and show the package insert or the label to the physician.

Adverse Reactions

In the pivotal clinical trial, a total of 125 dogs with chronic osteoarthritis were treated with ONSIOR at a robenacoxib dosage of 1-2 mg/kg once daily for 3 months. Adverse events reported at a frequency of more than 1% in the ONSIOR group are listed in the table below (by frequency and in alphabetical order:

Adverse Event

ONSIOR (number of dogs)

ONSIOR (% of total 125 dogs treated)

Positive control drug (number of dogs)

Positive control drug (% of total 63 dogs treated)

Emesis

18

14%

7

11%

ALT increased ≥ 3 times normal values after starting treatment

17

14%

4

6%

Diarrhea

16

13%

11*

17%

Anorexia

9

7%

3

5%

Polyphagia

7

6%

2

3%

Death

5

4%

2

3%

Lethargy

5

4%

2

3%

Cardiovascular disorder

3

2%

0

0%

Dyspnea

3

2%

0

0%

Gastroenteritis

3

2%

1**

2%

Hepatopathy with clinical signs

3

2%

2

3%

Intestinal stasis

3

2%

1

2%

Lameness

3

2%

2

3%

Polydipsia

3

2%

2

3%

Hypersalivation

2

2%

0

0%

Inappropriate urination

2

2%

0

0%

Pain

2

2%

0

0%

Seizure

2

2%

0

0%

Stomatitis

2

2%

0

0%

* including one case of hemorrhagic diarrhea

** hemorrhagic gastroenteritis

The following adverse events were reported at a frequency of less than 1% in the Onsior group: anxiety, gastric torsion, hyperactivity, polyuria, pruritus, somnolence, tenesmus and urinary incontinence.

Three dogs treated with ONSIOR and two treated with the positive control article had liver associated adverse events during the study. One ONSIOR treated dog was a 14 year old Collie with signs of polydipsia, vomiting and anorexia after 36 days of treatment. Liver values were normal at the start of treatment, and on day 42 ALT, ALP and AST values were all increased. Treatment was stopped and 1 month later the dog had recovered. In the second case, a 10 year old dog treated with ONSIOR started vomiting, was polyuric and polydipsic, and was lethargic on the 33rd day of treatment. The dog entered the study with an increased ALT and on day 27 of the study there were marked increases in ALT, ALP and AST. Treatment was stopped and the dog recovered 6 weeks later. In the third ONSIOR case, a 12 year old German Shepherd had severe vomiting, diarrhea, abdominal pain and was lethargic and anorexic after 26 days of treatment. At the start of the study ALT and ALP were increased, however by day 28 of treatment there was a large increase in ALT, ALP and AST values. A liver biopsy showed severe active hepatitis. The dog died the day following the liver biopsy. In the positive control group, one dog, an 11 year old Great Pyrenees Mountain, developed a fatty liver one week after starting treatment. This dog had mild increases in liver enzymes at the start of treatment and the values increased slightly with treatment. The second positive control dog, a 13 year old Labrador retriever, was polydipsic and lethargic 5 days after starting treatment. By day 56 the dog had lost more than 10% of its body weight and treatment was stopped. The dog had increased liver enzymes at inclusion and the values increased with treatment. These cases show the importance of ensuring no liver abnormalities are present before starting treatment.

One ONSIOR treated dog, an 11 year old Labrador Retriever, had vomiting, hematochezia and anorexia after 56 days treatment. Values of ALT, ALP and AST were increased in the dog. However no link between the gastrointestinal signs and hepatic disease was made by the treating veterinarian. The treatment was stopped and 1.5 months later the dog had recovered.

Of the 17 dogs treated with ONSIOR that had normal ALT values at the start of the study that increased to 3x normal during the study, 10 dogs had no clinical signs, 4 dogs had mild signs of soft feces or vomiting and three dogs had severe clinical signs of vomiting, lethargy and anorexia. None of the 4 dogs treated with the positive control article that had ALT values 3x normal had clinical signs.

Information For Dog Owners

ONSIOR is the product your veterinarian has chosen to treat your dog’s arthritis pain. It belongs to a class of drugs called “Non-steroidal Anti-inflammatory” or NSAIDs. These drugs must be used according to your veterinarian’s directions. Occasionally, NSAIDs can cause side effects. If your dog stops eating, is depressed, vomits or has diarrhea stop the drug immediately and contact your veterinarian. In most cases the side effects will disappear when the drug is stopped but in rare cases it may be serious. For this reason, it is important to consult with your veterinarian. If you notice any serious side effects or others not mentioned in this insert, please inform your veterinarian.

Pharmacology

Mode of Action

Pharmacodynamics

Robenacoxib is an NSAID of the coxib class. It is a highly potent and selective inhibitor of the cyclooxygenase 2 enzyme (COX-2). The cyclooxygenase enzyme (COX) is present in two forms. COX-1 is the “constitutive” form of the enzyme and has protective functions including in the gastrointestinal tract and kidney. COX-2 is the “inducible” form of the enzyme and is responsible for the production of mediators including PGE2 which induce pain, inflammation or fever.

Pharmacokinetics

Absorption: After oral administration of robenacoxib flavoured tablets at 1 mg/kg without food, peak blood concentrations are attained rapidly with a Tmax of 0.5 h, a Cmax of 1124 ng/ml and an AUC of 1249 ng.h/ml.

In a canine pharmacokinetic study, co-administration of tablets with the entire daily ration of food reduced the AUC by 22% (bioavailability was 62% with food versus 84% when fasted) and the Cmax by 15% (Cmax was 917 ng/ml with food versus 1076 ng/ml when fasted). However, Tmax was not delayed with food (0.3 h) as compared to when fasted (0.5 h). The terminal half-life was 1.15 hours with food as compared to fasted (0.86 h); this difference is very small but may indicate a slower absorption of part of the ingested robenacoxib with food. In an efficacy study with osteoarthritic dogs using ONSIOR, the efficacy was slightly but significantly better when robenacoxib tablets were administered without food.

Distribution: Robenacoxib has a relatively small volume of distribution (Vss 240 ml/kg) and is highly bound to plasma proteins (>98%).

Biotransformation: Robenacoxib is extensively metabolized by the liver in dogs. Apart from one gamma-lactam metabolite, the identity and activity of other metabolites is not known in dogs.

Elimination: Robenacoxib is cleared rapidly from blood (CL 0.81 L/kg/h) with an elimination half-life of 0.7 h after intravenous administration. After oral administration of flavoured tablets, the terminal half-life in blood was 1.2 h. Robenacoxib persists longer and at higher concentrations at sites of inflammation than in blood. Robenacoxib is excreted predominately via the biliary route (56%) and the remainder via the kidneys. The pharmacokinetics of robenacoxib do not differ between male and female dogs.

Safety Studies

In a 6 month study, 6-7 month old healthy Beagle dogs (4/sex/group) were administered ONSIOR at doses of 0, 1X (2.0 mg/kg), 3X (6.0 mg/kg) or 5X (10 mg/kg) once daily as oral tablets.

All dogs survived to their scheduled termination at the end of the six-month study. No effect of treatment was observed on clinical findings, food consumption, water consumption, buccal mucosal bleeding time, ophthalmoscopic, electrocardiographic, physical and neurological examinations, hematology, coagulation, urinalysis, fecal findings and microscopic examinations.

Vomiting, soft feces, injected sclera and salivation were commonly observed in the treated and control groups. Pooled body weights of animals at the 1X dose were slightly higher, but statistically significant, compared to controls during weeks 8 through 14. Albumin was slightly lower compared to the controls in the 3X group on day 91 and in the 1X and 5X groups on day 181. Mean ovarian weights were significantly decreased in the females of the 3X and 5X groups when compared to the controls. These changes appeared to be test article related but there were no histopathological changes. There was a red locus on the cecum of a 3X male and on the duodenum of a 5X female. These lesions were not associated with intestinal erosions on histopathology.

Individual blood profiles of all animals from all treatment groups showed large inter-animal variation on study Days 1, 30, and 150. The Cmax and AUC data determined for Days 1, 30, and 150, considering the large inter-animal variation, reached comparable levels with no accumulation except for the 1X dose. In the 1X dose, data from Day 30 to Day 150 showed a strong increase in the mean Cmax and AUC; no similar trend was seen in the data from study Day 1 to Day 30. Blood concentrations were below the limit of detection within 24 hours postdose in the 1X and 3X groups for all animals at all time points. For the 5X group, a few animals on Day 30 and Day 50 had low but detectable blood levels at 24 hours postdose, with a majority of the animals exhibiting blood concentrations below the limit of quantification. In general, the Cmax and AUC data showed a dose-related increase between the three dose groups.

The daily oral administration of ONSIOR at 1X, 3X, and 5X the maximum target exposure in adult Beagle dogs was well tolerated in this 6-month study. Nevertheless it is strongly recommended that the dose of ONSIOR be tapered to the lowest effective dose and that liver enzymes be monitored regularly.

Efficacy Study

Efficacy was demonstrated using ONSIOR in a blinded, positive-controlled, multi-centered field study conducted in France involving client owned dogs. In this study dogs with clinical signs of osteoarthritis of at least 3 weeks duration confirmed by radiographic changes and lameness were randomly assigned to receive treatment with 1-2 mg/kg ONSIOR or the positive control article for up to 12 weeks. There were 125 dogs in the ONSIOR group and 63 dogs in the positive control group. The primary endpoint was a global investigator score, a composite score for posture, lameness at walk and trot, willingness raise the contralateral limb and pain on palpation/mobilization. One dog in each group was withdrawn because of lack of efficacy. Eleven dogs (9%) in the ONSIOR group and 5 dogs (8%) in the positive control group were withdrawn because of adverse events which may or may not have been related to the treatment. The efficacy of robenacoxib was demonstrated to be noninferior to the positive control for the primary endpoint. The results of the study demonstrated that the efficacy of ONSIOR was noninferior to the positive control treatment.

STORAGE CONDITIONS:

ONSIOR should be stored at 5-25°C.

PRESENTATION:

ONSIOR is available in 5, 10, 20 and 40 mg tablet strengths in colour-coded packaging for oral administration.

Date: March 2013

DIN 02374692 (5 mg), 02374706 (10 mg), 02374714 (20 mg), 02374722 (40 mg)

Novartis Animal Health Canada Inc., 2000 Argentia Road, Plaza 3, Suite 400, Mississauga, Ontario L5N 1V9

™Trademark of Novartis AG; used under license.

NAH-ONSK9-TB-CAN-PI-1

611598 CAN 912988

NAC No.: 1231110.0

NOVARTIS ANIMAL HEALTH CANADA INC.
2000 ARGENTIA RD., SUITE 400, PLAZA 3, MISSISSAUGA, ON, L5N 1V9
Telephone:   800-387-6325
Order Desk:   800-387-6325
Fax:   905-567-0221
Fax Orders:   800-827-5782
Website:   www.ah.novartis.ca
Email:   ah.questions@novartis.com
Every effort has been made to ensure the accuracy of the Onsior (tablets for dogs) (40 mg) information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.

Copyright © 2014 North American Compendiums. Updated: 2014-05-28

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