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Onsior Solution for Injection (Canada)

This page contains information on Onsior Solution for Injection for veterinary use.
The information provided typically includes the following:
  • Onsior Solution for Injection Indications
  • Warnings and cautions for Onsior Solution for Injection
  • Direction and dosage information for Onsior Solution for Injection

Onsior Solution for Injection

This treatment applies to the following species:
Manufacturer: Elanco (Novartis)

(robenacoxib)

Solution for Injection

(Robenacoxib 20mg/mL sterile solution)

Non-Steroidal Anti-Inflammatory

FOR VETERINARY USE ONLY

DIN: 02374382

Description

ONSIOR is a clear, colourless sterile solution containing the active ingredient, robenacoxib, 20 mg/mL.

THERAPEUTIC CLASSIFICATION:

ONSIOR is a non-steroidal anti-inflammatory drug (NSAID) belonging to the coxib class.

Onsior Solution for Injection Indications

DOGS:

ONSIOR is indicated for the relief of pain and inflammation associated with orthopedic or soft tissue surgery.

CATS:

ONSIOR is indicated as an adjunctive medication in the control of postoperative pain and inflammation associated with onychectomy, ovariohysterectomy, and castration in cats.

Dosage and Administration

DOGS:

Administer subcutaneously once approximately 30 minutes before the start of surgery, around the time of induction of general anesthesia, at a dose of 2 mg/kg (1 mL per 10 kg of body weight).

CATS:

Carefully consider the potential benefits and risks of Onsior and other treatment options before deciding to use Onsior (robenacoxib injection). Use the lowest effective dose for the shortest duration consistent with individual response.

The dose of ONSIOR is 2 mg/kg subcutaneously once daily, for a maximum of three days. Administer the initial dose of ONSIOR subcutaneously to cats approximately 30 minutes before the start of surgery, around the time of induction at a dose of 2 mg/kg. To ensure accuracy of dosing, the use of a 1 mL graduated syringe is recommended.

Contraindications

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

● dogs and cats with gastro-intestinal ulcers;

● dogs and cats with impaired cardiac, renal or hepatic function or coagulation abnormalities;

● dogs and cats that are dehydrated, hypovolemic, hypoproteinemic or hypotensive;

● dogs and cats with a known hypersensitivity to robenacoxib or ONSIOR excipients or known intolerance to NSAIDS;

● concurrent use of other NSAIDs or corticosteroids;

● dogs and cats used for breeding or that are pregnant or lactating dogs and cats because the safety of robenacoxib has not been established in these animals.

CAUTIONS:

The safety of ONSIOR has not been established in dogs and cats less than 2.5 kg (5.5 lbs.) or in dogs less than 6 months of age and in cats less than 4 months of age.

All dogs and cats 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.

As anesthetics may affect renal perfusion, the use of parenteral fluid therapy and monitoring of blood pressure during surgery should be considered to decrease the potential renal complications when using NSAIDs peri-operatively.

The adequacy of the analgesia should be assessed regularly following extubation. If additional analgesia is required choose a drug not of the anti-inflammatory class if it is to be administered within the 24 hours of treatment with ONSIOR.

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 is an increased risk of renal toxicity.

Pretreatment with other anti-inflammatory drugs 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.

Appetite should be monitored in dogs and cats receiving Onsior. Stop administration of Onsior if appetite decreases or the cat or dog becomes lethargic.

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.

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

Robenacoxib has been shown to prolong the QT interval in cats. The risk of developing a ventricular arrhythmia is unknown. The use of ONSIOR in cats with cardiac disease has not been studied. The use of robenacoxib with other drugs shown to prolong the QT interval is not recommended. Commonly used drugs that prolong the QT interval include antihistamines, prokinetics and certain anesthetic drugs.

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

Although all adverse events are not reported, the following information is based on voluntary post-approval drug experience reporting. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using this data.

The post-marketing adverse event reports for ONSIOR injectable have shown the following signs to be reported very rarely (less than 1 animal in 10,000 animals, including isolated reports):

Dogs: anorexia, emesis, lethargy, diarrhea

Cats: anorexia, emesis, lethargy, injection site necrosis

DOGS:

In the pivotal clinical trials, a total of 215 dogs received ONSIOR prior to orthopedic or soft tissue surgery. The following adverse events were reported with ONSIOR with a frequency >1% on the day of surgery or the following day:

Table 1: Adverse Events in Dogs Undergoing Orthopedic Surgery

Adverse Events

ONSIOR (n=97 dogs)

Positive control (n=43 dogs)

Pain at injection site

4 (4%)

3 (7.5%)

Diarrhea

2 (2%)

0 (0%)

Adverse Events occurring in <1% of dogs in the ONSIOR group: vomiting and decreased appetite.

Table 2: Adverse Events in Dogs Undergoing Soft Tissue Surgery

Adverse Events

ONSIOR (n=118 dogs)

Positive control (n=56 dogs)

Pain at injection site

9 (7.6%)

8 (14%)

Vomiting

7 (5.9%)

1 (1.8%)

Hypersalivation

2 (1.7%)

0 (0%)

Increased bleeding

2 (1.7%)

0 (0%)

CATS:

The controlled field study included a total of 349 healthy male and female cats in the field safety analysis. ONSIOR treated cats represented 7 breeds, 4 months to 7 years old, weighing 2.5-6.0 kg. The following table shows the number of cats exhibiting each adverse reaction.

Table 3: Adverse Reactions in the Postoperative Pain Field Study

Adverse Reaction*

ONSIOR (n = 174 cats**)

Control (n = 175 cats)

Incision site infection, dehiscence

9 (5.2%)

0 (0%)

Increased incision site bleeding

6 (3.4%)

4 (2.3%)

Vomiting

5 (2.9%)

0 (0%)

Decreased appetite

4 (2.3%)

3 (1.7%)

Lethargy (after day of surgery)

4 (2.3%)

2 (1.1%)

Urinary Tract Infection (UTI)

2 (1.1%)

0 (0%)

Semiconscious***

1 (0.6%)

0 (0%)

Coughing

1 (0.6%)

0 (0%)

Fever

1 (0.6%)

0 (0%)

Soft stool, diarrhea

0 (0%)

2 (1.1%)

*Cats may have experienced more than one type or occurrence of an event during the study. **One ONSIOR cat suffered an anesthetic-related death.

***Semiconscious cat fully recovered.

No clinically significant differences existed between the ONSIOR and the control group for hematology, serum chemistry or urinalysis results or for injection site evaluation.

OTHER INFORMATION:

Clinical Pharmacology

Mode of Action

Pharmacodynamics

Robenacoxib is a selective inhibitor of the cyclooxygenase 2 enzyme (COX-2), in vitro. The clinical relevance of this data has not been shown. 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

DOGS:

Absorption: Peak blood concentrations of robenacoxib are attained rapidly after subcutaneous injection of ONSIOR in dogs. After a dosage of 2 mg/kg a Tmax of 1 h, a Cmax of 615 ng/mL and an AUC(0-) of 2180 ng.h/mL is obtained. After a subcutaneous administration of 1 mg/kg the systemic bioavailability is 88%.

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

Metabolism: 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.

Elimination: After intravenous administration robenacoxib is rapidly cleared from blood (CL = 0.81 L/kg/h in dogs) with an elimination half-life (t1/2) of 0.8 h. After subcutaneous administration, the terminal half-life from blood is 1.2 h. Robenacoxib persists longer and in higher concentrations at sites of inflammation than in blood. Robenacoxib is excreted predominately via the biliary route in dogs (~65%) and the remainder via the kidneys. The pharmacokinetics of robenacoxib does not differ between male and female dogs.

CATS:

Absorption: Peak blood concentrations of robenacoxib are attained rapidly after subcutaneous injection of ONSIOR in cats. After a dosage of 2 mg/kg a Tmax of 1 hour, a Cmax of 1464 ng/mL and an AUC(0-) of 3128 ng.h/mL is obtained. ONSIOR has a systemic bioavailability of 69%, which is less than that observed after an equivalent oral dose. A slightly less than dose-proportional increase in exposure was observed with an increase in dose (a 2X dose resulted in a 1.4X increase in drug exposure; a 3X increase in dose resulted in a 2.3X increase in drug exposure).

Distribution: Robenacoxib has a relatively small volume of distribution (mean Vss = 190 mL/kg) and is highly bound to plasma proteins (>99%). Robenacoxib persists longer in the inflammatory exudate of a tissue cage model than in blood. The median robenacoxib elimination half-life in exudate was about 27 hours versus 2.5 hours for blood.

Metabolism: Robenacoxib is extensively metabolized by the liver in cats. Apart from one lactam metabolite, the identity of other metabolites is not known.

Elimination: Robenacoxib is rapidly cleared from blood (mean clearance [CL] = 0.44 L/kg/h) with an elimination mean half-life (t1/2) of 1.1 hours after intravenous administration. After subcutaneous administration, the terminal half-life was 1.1 hour (range of estimated values was 0.9 hour to 1.6 hours). Repeated subcutaneous administration at dosages of 2 -20 mg/kg produced no change in the blood profile, with neither bioaccumulation of robenacoxib nor enzyme induction. Elimination occurs predominantly through the biliary route (fecal and urinary excretion are 60 and 16.5% respectively). The pharmacokinetics of robenacoxib injection does not differ between male and female cats.

Safety And Efficacy Study Information:

DOGS:

Safety

Six month-old beagle dogs were administered ONSIOR by subcutaneous injection at dosages of 2 mg/kg (therapeutic dose), 6 mg/kg (3X overdose), and 20 mg/kg (10X overdose) once daily for 3 days every other week for 3 cycles. There was a higher incidence of pain on injection in the 10X males and 3X and 10X females. One 3X dog developed a heart murmur during the study. It is not known if the murmur was related to the treatment. Other observed changes included lower body weights in males in the 1X, 3X and 10X groups and females in the 1X and 10X groups compared to the control. There were no detectable pathological changes to the gastrointestinal tract, kidney or liver. There were no clinically significant changes to bleeding time. Reversible inflammation at the injection site was noted in all groups (including controls) and was more severe in the 6 and 20 mg/kg dose groups. As with any NSAID, overdose may cause gastrointestinal, kidney, or liver toxicity in sensitive or compromised animals.

Efficacy

Efficacy was demonstrated using ONSIOR in two blinded positive controlled multi-centered field studies conducted in France and Germany involving client-owned dogs. In one study dogs requiring orthopedic surgery such as repair of a ruptured anterior cruciate ligament, fracture, femoral neck excision, fragmented coronoid or osteochondrosis dissecans lesion surgery were randomly assigned to receive treatment with 2 mg/kg ONSIOR or the positive control article once. In the second study dogs undergoing soft tissue surgery, most commonly ovariectomy, ovariohysterectomy or mammary gland chain excision were randomly assigned to treatment with 2 mg/kg ONSIOR or the positive control once. There were 97 dogs enrolled in the ONSIOR group and 43 dogs in the positive control group in the orthopedic surgical study and 118 dogs in the ONSIOR group and 56 dogs in the positive control group for the soft tissue surgical study. The mean age of the dogs was 4 years in the orthopedic study and 5 years for the soft tissue study. In both studies the primary endpoint was the sum of the Glasgow Pain Scale scores conducted at 1, 2, 4, 8 and 24 hours postoperatively. There were no dogs which required rescue therapy in either study. There were no differences in the number of dogs that were withdrawn for adverse events between the treatment groups. In both studies noninferiority was demonstrated for the primary endpoint. The results of the studies demonstrated the efficacy of ONSIOR was noninferior to the positive control treatment.

CATS:

Safety

1-day Target Animal Safety Study: In a laboratory study, ONSIOR (robenacoxib) was administered once at 2 (subcutaneously or intravenously) or 4 mg/kg (2x intravenously) to cats anesthetized with intramuscular ketamine and medetomidine. Treatment was associated with vomiting (after intravenous administration of ONSIOR at 2 and 4 mg/kg). One female cat given 2 mg/kg intravenously had a supraventricular premature complex and/or an escape rhythm at 5 minutes post dose, but no QT interval changes were detected at 5 or 60 minutes post administration. A statistical evaluation for ECG parameters was not conducted between the control cats and the cats administered 2 mg/kg subcutaneously. However, the cats administered 2 mg/kg subcutaneously were compared statistically to the cats administered 2 mg/kg intravenously and were not statistically different from each other.

37-Day Interchangeable Use Study: ONSIOR was administered orally (6 mg tablets) and subcutaneously (20 mg/mL solution) to 4-month old healthy cats at 0, 1, 2, and 3 times the labeled doses (1X = 2.4 mg/kg/day orally based on the inherent tablet dose band or 2.0 mg/kg/day subcutaneously). Interchangeable use was evaluated by alternating three 7-day oral tablet/3-day subcutaneous injection cycles followed by one final 7-day oral tablet dosing cycle. Findings included: elevated creatine kinase levels on Days 13 and 37, soft stools, histologic observation of a minimal oral (tongue) ulceration in a 1X cat, injection site edema for up to 120 hours prior to resolution, and a prolonged QT interval in treated cats as compared to the controls on Day 36. Histologically, the injection site had minimal or mild, subacute/chronic inflammation. Inflammation at the injection site was observed in both treated and control animals with a greater frequency in the higher dose groups than in the control and 1X groups. One male and one female in the 1x group had focal tubular degeneration/regeneration of the renal cortex. Focal tubular regeneration represents non-specific renal findings which can occur as a result of many causes. Dose-normalized AUC and concentration levels were higher following the oral route than the subcutaneous route. There was no significant accumulation following once daily administration. One 2X-treated cat had a 7-fold increase in buccal mucosal bleeding time (BMBT) during the treatment period compared to the pre-treatment value.

Preliminary 37-Day Interchangeable Use Study: ONSIOR was administered orally (6 mg tablets) and subcutaneously (20 mg/mL solution) to 4-month old cats at 0, 1, and 5 times the labeled doses (1X = 2.4 mg/kg/day orally based on the inherent tablet dose band or 2.0 mg/kg/day subcutaneously). Interchangeable use was evaluated by alternating three 7-day oral tablet/3-day subcutaneous injection cycles followed by one final 7-day oral tablet dosing cycle. Clinical findings included: scabs and sores at the injection sites of one 1X female and two 5X females, and injection site edema noted more frequently in treated cats. Injection site changes were characterized as minimal to moderate granulomatous inflammation, minimal to moderate fibroplasia/fibrosis, and minimal myofiber regeneration of the panniculus carnosus. In one 1X female, moderate necrosis of a blood vessel was noted within the granulomatous inflammation. Minimal myofiber regeneration was observed in the underlying skeletal muscle in three out of four 5X males.

A red depressed area on the upper lip of one 5X cat correlated histologically with a minimal ulcer. Creatinine was significantly increased in 5X cats compared to the controls. Urine specific gravities remained within normal limits for all 5X cats, and blood urea nitrogen (BUN) values remained within normal limits for all study animals. Histologically, renal changes included bilateral or unilateral minimal to moderate vacuolation and bilateral or unilateral minimal to mild degeneration of proximal tubules were observed in three 5X males. Two 5X males had mineralized foci in the epithelium covering the papilla.

One 5X female had a brief episode of ataxia and lethargy on Day 16. This cat was subsequently noted to be dehydrated and constipated, requiring veterinary intervention with subcutaneous fluid therapy and nutritional supplementation. This cat had the greatest QT increase on ECG evaluation.

Efficacy

Effectiveness was demonstrated using ONSIOR (robenacoxib 20 mg/mL sterile solution) in a masked, placebo-controlled, multi-site field study involving client-owned cats. In this study, 349 cats presenting for ovariohysterectomy or castration in conjunction with an onychectomy (forelimbs only) were randomly administered ONSIOR or saline (control), along with butorphanol and a metacarpal 4 point ring block using bupivacaine. The drug was administered approximately 30 minutes prior to surgery along with pre-anesthetic medications and continued once daily for two additional treatments. Effectiveness was evaluated in 348 cats (173 treated and 175 controls) and field safety was evaluated in 349 cats. A statistically significant difference in the proportion of treatment successes calculated using the least mean squares in the ONSIOR treatment group (83.5%) compared to the control group (61.9%) was observed. Statistically significant differences for pain elicited on palpation at the spay or castration incision site, paw pain, behaviour following social interaction and from a distance, posture score and overall pain at various post-surgical time points up to 8 hours were also observed. Thirty-four out of 173 robenacoxib cases and 73 out of 175 placebo cases were treatment failures. Of the 107 treatment failures (robenacoxib and control), 91 cases (85% of failures) were rescued/withdrawn by 8 hours post surgery. Sixteen failures were rescued/withdrawn between 24 and 28 hours post surgery (15% failures). The results of the field study demonstrate that ONSIOR when administered for a maximum of three days, is effective and well-tolerated for the control of postoperative pain associated with onychectomy, ovariohysterectomy and castration in cats.

STORAGE INFORMATION:

ONSIOR should be stored refrigerated at 2 - 8°C. Avoid introduction of contamination. Keep the vial in the outer carton. After broaching of the vial, the product may be stored for 28 days.

HOW SUPPPLIED INFORMATION:

ONSIOR is available in a multi-dose amber glass vial.

Date: April 2016

Elanco Canada Limited, 150 Research Lane, Suite 120, Guelph, Ontario N1G 4T2

Elanco, Onsior and the diagonal bar are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries or affiliates.

08Apr2016

CPN: 1231114.2

ELANCO CANADA LIMITED
Distributed by ELANCO, Division Eli Lilly Canada Inc. & ELANCO CANADA LIMITED (successor to Novartis Animal Health Canada Inc.)
RESEARCH PARK CENTRE, 150 RESEARCH LANE, SUITE 120, GUELPH, ON, N1G 4T2
Telephone:   519-821-0277
Order Desk:   800-773-7603
Fax:   519-821-7831
Elanco Canada Limited Customer Service Telephone:   800-387-6325
Elanco Canada Limited Customer Service Fax:   800-827-5782
Website:   www.Elanco.ca
Every effort has been made to ensure the accuracy of the Onsior Solution for Injection 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 © 2016 North American Compendiums. Updated: 2016-10-31

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