Robenacoxib

Overview

Robenacoxib (Onsior®) is a selective COX-2 inhibitor NSAID used in dogs and cats for the management of pain and inflammation associated with musculoskeletal disorders and surgical procedures.

It is approved for the treatment of both acute and chronic musculoskeletal pain and inflammation and for the control of postoperative pain and inflammation; in the United States the approval covers postoperative use only, for a maximum of three days. Robenacoxib is characterized by tissue selectivity, with preferential distribution to sites of inflammation and a short plasma half-life.

Mechanism of Action (MOA): Robenacoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, reducing the production of prostaglandins involved in inflammation and pain.

Indications

Robenacoxib is used in dogs and cats for the management of pain and inflammation associated with musculoskeletal disorders and surgery.

• Acute and chronic musculoskeletal disorders: Alleviation of pain and inflammation in dogs and cats.
• Postoperative pain and inflammation (dogs): Reduction of pain and inflammation following orthopedic and soft tissue surgery.
• Postoperative pain and inflammation (cats): Reduction of pain and inflammation following orthopedic surgery, ovariohysterectomy and castration in cats; robenacoxib is the only NSAID approved for multiple doses in cats in the United States.
• Chronic osteoarthritis (dogs): Long-term control of the pain and inflammation of chronic osteoarthritis in dogs; outside the United States the oral tablets carry this indication.
• Anterior uveitis (cats): Extra-label control of the ocular pain and inflammation of anterior uveitis in cats, for a maximum of three days.

Dosage (Reference)

Dog

Robenacoxib may be administered by subcutaneous injection or orally for the management of pain and inflammation.

Cat

Robenacoxib may be administered by subcutaneous injection or orally for the management of acute and chronic musculoskeletal pain and inflammation.

Warnings & Precautions

Robenacoxib should be used cautiously in patients at risk of renal, gastrointestinal, or cardiovascular complications and careful dose administration is particularly important in cats.

• Perioperative use: NSAIDs may adversely affect renal perfusion during periods of hypotension. If hypotension during anesthesia is anticipated, delay administration until the patient has fully recovered and is normotensive.
• Renal disease: Administration to animals with renal disease should be carefully evaluated and is not advisable during the perioperative period.
• Dehydration, hypovolemia, or hypotension: Avoid use in dehydrated, hypovolaemic or hypotensive patients; some references instead advise cautious use.
• Gastrointestinal disease: Avoid use in animals with gastrointestinal disease; gastrointestinal ulceration is specifically contraindicated, while other references frame pre-existing gastrointestinal disease as an increased-risk condition.
• Coagulation disorders: Do not administer to animals with blood clotting disorders.
• Age and body weight restrictions: Do not administer to dogs younger than 12 weeks, cats younger than 16 weeks, or animals weighing less than 2.5 kg; some references set a single minimum age of 4 months for both species.
• Pregnancy: Avoid use during pregnancy; some references do not prohibit it and advise that the drug should only be used when the maternal benefit outweighs the potential risk to offspring. Safety has not been established during lactation or in animals used for breeding.
• Liver disease: Hepatic disease may prolong the metabolism of robenacoxib, increasing the risk of drug accumulation with repeated dosing. Use with caution in dogs and cats with hepatic dysfunction; on some labels hepatic dysfunction is a contraindication.
• Long-term therapy: Monitor clinical efficacy and adverse effects, with baseline and periodic blood count, renal chemistry with electrolytes, and urinalysis. For long-term therapy, check serum liver chemistry at 2, 4 and 8 weeks and then every 3 to 6 months, and discontinue treatment if liver enzyme activity rises markedly or is accompanied by clinical signs.
• Hypersensitivity and NSAID intolerance: Do not use in animals that are hypersensitive to robenacoxib, that have a known intolerance to NSAIDs, or that have gastrointestinal ulcers.
• Sulfite hypersensitivity: The solution for injection contains sodium metabisulfite and should not be used in animals with sulfite hypersensitivity.
• Cardiac disease and QT prolongation: Robenacoxib prolongs the QT interval; use it with caution in animals with cardiac disease and avoid combining it with other QT-prolonging drugs. Where the combination cannot be avoided, monitor carefully.
• Inappetence and lethargy: Stop administration in animals that become inappetent or lethargic.
• Peri-operative fluid therapy: When an NSAID is used peri-operatively, fluid therapy during surgery is recommended to reduce the risk of renal complications.
• Route of injection: Give the injection subcutaneously only; avoid intramuscular and intravenous injection.

Drug Interactions

Concurrent administration of robenacoxib with certain medications may increase the risk of adverse effects, particularly renal and gastrointestinal complications.

• Other NSAIDs: Do not administer concurrently or within 24 hours of another NSAID.
• Glucocorticoids: Do not administer concurrently with glucocorticoids; concurrent use is contraindicated. Recommendations for the treatment-free interval range from at least 24 hours to 3 to 5 days; take the pharmacokinetics of the previously used drug into account.
• Aminoglycosides and other potentially nephrotoxic drugs: Concurrent administration is not recommended because of the potential for increased nephrotoxicity.
• Diuretics and ACE inhibitors: Use cautiously with diuretics and ACE inhibitors, which affect renal blood flow; additional clinical monitoring is recommended. NSAIDs can reduce the blood-pressure effect of ACE inhibitors and the saluretic and diuretic effect of furosemide.
• Concurrent aspirin: Aspirin may increase the risk of gastrointestinal toxicity, including ulceration, bleeding, vomiting and diarrhea.
• Digoxin: NSAIDs may increase serum digoxin concentrations.
• Concurrent fluconazole: Fluconazole has increased plasma concentrations of a related coxib in humans and could potentially affect robenacoxib concentrations in dogs.
• Highly protein-bound drugs: Robenacoxib is more than 99% bound to plasma proteins and could theoretically displace other highly bound drugs such as oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas and valproic acid. These interactions are unlikely to be clinically important because increased free drug concentrations equilibrate through increased clearance, but monitor for adverse effects of each drug.
• Methotrexate: Serious toxicity has occurred when NSAIDs have been used with methotrexate; use the combination with extreme caution.
• Wash-out before switching NSAIDs: Allow a treatment-free period of at least 24 hours before starting robenacoxib after another anti-inflammatory, taking the previous drug’s pharmacokinetics into account; some guidance recommends a 3 to 5 day wash-out when switching NSAIDs.

Side Effects & Overdose

Side Effects

Gastrointestinal adverse effects are the most commonly reported reactions associated with robenacoxib therapy.

• Gastrointestinal signs: Commonly reported – decreased appetite, vomiting, soft feces and diarrhea – although most cases are mild and resolve without treatment. Stop therapy if signs persist beyond 1 to 2 days.
• Gastrointestinal bleeding: Discontinue treatment immediately if gastrointestinal bleeding is suspected.
• Cardiac effects: NSAIDs may precipitate cardiac failure in humans; the significance of this risk in animals is unknown.
• Adverse effects reported in dogs: Blood in the feces has been seen in some dogs, and increased liver enzymes were common in dogs given robenacoxib for longer than 2 weeks. Long-term oral treatment may raise liver enzyme activity without necessarily indicating liver pathology.
• Adverse effects reported in cats: Infection, dehiscence and increased bleeding at incision sites, decreased appetite, vomiting, lethargy and pain at the injection site have all been reported.
• Reactions at the injection site: Injection site reactions including swelling, necrosis and abscess formation have been reported; rotate injection sites when repeat doses are given.

Overdose

Repeated administration in patients with impaired hepatic function may increase the risk of drug accumulation and overdose.

• Drug accumulation: Liver disease may prolong the metabolism of robenacoxib, increasing the potential for accumulation with repeated dosing.
• Acute overdose: No acute toxicity data have been located. Acute overdose may cause gastrointestinal, kidney or liver toxicity.
• Safety margin in dogs: In dogs, 10 mg/kg daily for 6 months and 40 mg/kg (20 times the label dose) for 1 month produced no significant clinical, hematological or pathological effects. Oral robenacoxib given daily for 21 days produced microscopic colonic mucosal lesions in 4 of 7 healthy dogs, of uncertain clinical relevance.
• Safety margin in cats: In healthy young cats, 4 mg/kg subcutaneously every 24 hours for 2 days and 10 mg/kg subcutaneously for 3 consecutive days produced no signs of toxicity. Oral doses of 10 mg/kg every 24 hours for 28 days or every 12 hours for 42 days produced no toxicologically significant effects.
• Management: Treatment is supportive and based on clinical presentation, and may include gastrointestinal protectants and forced diuresis. Contact a 24-hour veterinary poison consultation service for a suspected overdose.

Key Notes

Practical clinical points for the use of robenacoxib in dogs and cats:

• Tissue selectivity: Robenacoxib preferentially distributes to and concentrates at sites of inflammation.
• Short plasma half-life: Plasma half-life is short despite sustained activity at inflamed tissues: about 0.9 to 1.2 hours after oral dosing and 1 to 4 hours after subcutaneous dosing in dogs, and about 1.7 hours orally and 1.1 hours subcutaneously in cats.
• Palatability in cats: The tablets are highly palatable, and many cats will consume them voluntarily.
• Oral administration in cats: Tablets may be administered directly or mixed with a small amount of food. A small amount of food does not significantly affect bioavailability, but a full meal can reduce oral bioavailability from about 49% to about 10%.
• Administration in dogs: Oral dosing is recommended without food because administration with food has been reported to reduce efficacy.
• COX-2 selectivity: In vitro whole-blood assays report about 128 to 130 times greater selectivity for COX-2 than COX-1 in dogs; reported feline ratios range from 32-fold to 500-fold. These ratios vary greatly with the assay used, and it is not established whether COX selectivity is associated with improved efficacy or safety.
• Pharmacokinetics: Oral bioavailability is about 84% fasted and 62% fed in dogs and about 49% fasted in cats; subcutaneous bioavailability is 67 to 100% in dogs and about 69% in cats. Robenacoxib is more than 98% protein bound, has a volume of distribution of about 0.24 L/kg in dogs and 0.19 L/kg in cats, and is eliminated mainly in the bile.
• Switching between tablets and injection: The tablets and the injection can be interchanged within a course in both species, up to the maximum number of doses. In cats the oral dose is not the same as the injectable dose, so recalculate when switching.
• Storage and handling: Store tablets at 15 to 25 degrees Celsius. Store the injection at 2 to 8 degrees Celsius in its original outer carton and use it within 12 weeks of first puncture. Tablets are not scored and must not be broken. Do not mix the injection with other drugs.