Onsior Solution for Injection for Cats (Canada)

Company: Elanco

(robenacoxib)

Solution for Injection

(robenacoxib 20mg/mL sterile solution)

Non-Steroidal Anti-Inflammatory

For Veterinary Use Only

For Subcutaneous Use in Cats

DIN 02374382

Description

ONSIOR contains robenacoxib which is a non-steroidal anti-inflammatory drug (NSAID) belonging to the coxib class. ONSIOR injection is a clear, colourless sterile solution containing the active ingredient, robenacoxib, 20 mg/mL.

INDICATION:

ONSIOR (robenacoxib) injection 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

For subcutaneous use in cats ≥ 4 months of age.

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 (robenacoxib) injection is 2 mg/kg subcutaneously once daily, for a maximum of 3 days. Administer the initial dose of ONSIOR subcutaneously to cats approximately 30 minutes before the start of surgery, around the time the pre-anesthetic agents are given, at a dose of 2 mg/kg. After surgery, once daily treatment may be given via subcutaneous injection, or interchanged with the oral tablet in cats ≥ 2.5 kg and ≥ 4 months of age, for up to a maximum of two additional days at their respective label recommended dose. If subsequent doses are given by subcutaneous injection, different sites for each injection should be used (see ADVERSE REACTIONS). To ensure accuracy of dosing, the use of a 1 mL graduated syringe is recommended.

Note: In cats, the dose of ONSIOR tablets and ONSIOR injection are different.

As with other NSAIDs, do not exceed the recommended dosage (see CONTRAINDICATIONS and CAUTIONS sections). When prescribing NSAIDs, exceeding the label recommended dose could lead to complications, including acute renal failure and in some cases associated death has been reported.

Owners should be advised when their pet has received a robenacoxib injection, and be informed of the potential for adverse reactions and clinical signs associated with possible NSAID intolerance. Always provide the Client Information Sheet to the pet owner after administration (detach from Package Insert).

Contraindications

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

● cats with gastro-intestinal ulcers;

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

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

● cats with a known hypersensitivity to robenacoxib or ONSIOR excipients or known intolerance to NSAIDs;

● concurrent use of other NSAIDs or corticosteroids;

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

CAUTIONS:

The safety of ONSIOR injection has not been established in cats less than 4 months of age.

All 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.

Monitor cats post-injection for reactions. Injection site reactions have been associated with the use of ONSIOR injection (See ADVERSE REACTIONS).

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. Cats that have experienced adverse reactions from one NSAID may experience adverse reactions from another NSAID. Patients at greatest risk for adverse events are those that are dehydrated, on concomitant diuretic therapy, or those with existing renal, cardiovascular, and/or hepatic dysfunction. Anesthetic drugs may affect renal perfusion; approach concomitant use of anesthetics and NSAIDs cautiously. Appropriate monitoring procedures (including ECG, blood pressure, and temperature regulation) should be employed during all surgical procedures. The use of parenteral fluids during surgery is recommended to decrease potential renal complications when using NSAIDs perioperatively.

Appetite should be monitored in cats receiving ONSIOR.

Do not give additional ONSIOR injections if decreased appetite, lethargy, vomiting, diarrhea, change in drinking or urination, change in behaviour, such as depression or restlessness, or other suspected adverse reactions occur (see ADVERSE REACTIONS).

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 following treatment with ONSIOR.

Pre-treatment 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.

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.

The use of concomitantly protein-bound or similarly metabolized drugs with ONSIOR (robenacoxib) has not been studied. Commonly used protein-bound drugs include cardiac, anticonvulsant, and behavioral medications. The influence of concomitant drugs that may inhibit metabolism of ONSIOR has not been evaluated. Drug compatibility should be monitored in patients requiring adjunctive therapy.

ONSIOR was administered concurrently with pre-anesthetic (opioid) and a metacarpal four point ring block using a longer acting local anesthetic medication, during the field study assessing the effect of ONSIOR on postoperative pain control. Level of analgesia should be monitored postoperatively to assess if additional pain control is needed. If necessary, additional analgesic treatment with opioids is recommended. Other NSAIDs and corticosteroids should not be used.

The use of ONSIOR in cats with cardiac disease has not been studied. ONSIOR has been shown to prolong the QT interval in a laboratory setting. The associated risk of developing a ventricular arrhythmia is unknown. 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. Appropriate monitoring procedures (including ECG, blood pressure, and temperature regulation) should be employed during all surgical procedures.

Warnings

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

Adverse Reactions

Although all adverse reactions 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 reaction frequency or establish a causal relationship to product exposure using this data.

The post-marketing adverse reaction reports for ONSIOR injectable very rarely (less than 1 animal in 10,000 animals, including isolated reports) reported anorexia, emesis, lethargy, and injection site necrosis.

The placebo 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 kg. The following adverse reactions were reported with ONSIOR with a frequency of more than 1% during the study.

Adverse Reactions in Cats in the Postoperative Pain Field Study

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

Adverse reactions reported at a frequency of less than 1% in the ONSIOR group: coughing, fever and 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.

For technical support or to report a suspected adverse drug reaction, contact Elanco Canada Limited at 1-800-265-5475.

Information for Cat Owners:

ONSIOR, like other drugs of its class, is not free from adverse reactions. Adverse reactions may include vomiting, diarrhea, decreased appetite, dark or tarry stools, increased water consumption, increased urination, anemia, yellowing of gums, skin or whites of the eye due to jaundice, lethargy, incoordination, seizure, or behavioural changes. Discontinue ONSIOR therapy and contact your veterinarian immediately if signs of possible intolerance are observed. The vast majority of patients with drug related adverse reactions have recovered when the signs are recognized, the drug is withdrawn, and veterinary care, if appropriate, is initiated.

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

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 h, 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 h versus 2.5 h for blood.

Biotransformation: 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 (t_1/2) of 1.1 h after intravenous administration. After subcutaneous administration, the terminal half-life was 1.1 h (range of estimated values was 0.9 h to 1.6 h). Repeated subcutaneous administration at dosages of 2 to 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 Studies:

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 anaesthetized 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 h 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 degeneration/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 Study

Effectiveness was demonstrated using ONSIOR (robenacoxib) injection 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 h 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 h post surgery. Sixteen failures were rescued/withdrawn between 24 and 28 h 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 CONDITIONS:

ONSIOR injection should be stored refrigerated at 2°C to 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 at room temperature (15°C - 25°C).

PRESENTATION:

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

Date: April 2023

Elanco Canada Limited, 1919 Minnesota Court, Suite 401, Mississauga, Ontario L5N 0C9

Onsior, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates.

© 2023 Elanco or its affiliates.

04Apr2023

CPN: 1231114.8