Surgical pain management in small animal medicine requires balancing efficacy with safety. Non-steroidal anti-inflammatory drugs (NSAIDs) are a cornerstone of multimodal analgesia, but their use is historically constrained by species-specific toxicities. This is particularly true in cats, whose unique liver metabolism (lacking glucuronidyltransferase pathways) makes them highly sensitive to NSAID-induced kidney damage and gastrointestinal ulceration.

Among veterinary NSAIDs, robenacoxib occupies a distinct clinical niche. It is a highly selective cyclooxygenase-2 (COX-2) inhibitor approved for both dogs and cats. Administered as a subcutaneous injection in the clinic around the time of surgery, robenacoxib provides rapid, targeted pain control.

Historically, this drug was available only under the brand name Onsior (manufactured by Elanco). However, the regulatory environment transitioned on March 9, 2026, when the U.S. Food and Drug Administration (FDA) approved the first generic robenacoxib injection (sponsored by Cronus Pharma under ANADA 200-804). This approval, alongside the January 2026 approval of the first generic robenacoxib tablets for cats (sponsored by ZyVet Animal Health), marks a new era of access for this critical surgical molecule.

This clinical guide reviews the indications, dosing protocols, cat-versus-dog label differences, safety margins, and openFDA adverse event data for robenacoxib injection. For the broader oral-tablet label, side effects, and NSAID washout (including the dog tablet's "Do not use in cats" rule), see our Onsior (robenacoxib) for dogs and cats guide.

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What is Robenacoxib? Selectivity and Pharmacokinetics

Robenacoxib is a non-steroidal anti-inflammatory drug belonging to the coxib class. Like all NSAIDs, it works by inhibiting the cyclooxygenase (COX) enzymes that convert arachidonic acid into prostaglandins—the chemical messengers that drive inflammation, pain, and fever.

However, robenacoxib was specifically engineered to be COX-2 selective:

• COX-1 (Constitutive): This enzyme is responsible for producing prostaglandins that perform baseline "housekeeping" functions in the body, such as maintaining blood flow to the kidneys, protecting the mucosal lining of the stomach, and supporting normal platelet aggregation.
• COX-2 (Inducible): This enzyme is upregulated by inflammatory stimuli and is the primary driver of postoperative pain, tissue swelling, and fever.

By preferentially binding to COX-2 while sparing COX-1, robenacoxib targets the site of surgical inflammation while minimizing the risk of adverse gastrointestinal and renal effects. In clinical trials, robenacoxib demonstrated high selectivity for canine and feline COX-2 in vitro and in vivo.

Pharmacokinetics and Tissue Selectivity

Robenacoxib exhibits a unique pharmacokinetic property known as target tissue selectivity. When administered, it is rapidly cleared from the bloodstream (with a short plasma half-life of approximately 1 to 2 hours in cats and dogs). However, it persists at the site of inflammation for much longer.

This occurs because the molecule binds tightly to the acidic environment of inflamed tissues. As a result, the patient benefits from prolonged, 24-hour localized pain relief, while the kidneys and gastrointestinal tract are spared from prolonged exposure in the systemic circulation.

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The 2026 Generic Approvals: A Regulatory Milestone

For more than a decade, Elanco's Onsior was the only robenacoxib product available to U.S. veterinarians. In early 2026, two generic approvals introduced therapeutic alternatives:

1. Feline Generic Tablets (January 9, 2026): The FDA approved the first generic robenacoxib tablets for cats, sponsored by ZyVet Animal Health. These tablets are bioequivalent to Onsior tablets, providing once-daily oral postoperative care.
2. Generic Injectable (March 9, 2026): The FDA approved Robenacoxib Injection, the first generic injectable robenacoxib, sponsored by Cronus Pharma Specialities India Private Ltd. under ANADA 200-804.

Bioequivalence and Formulation

Under the ANADA approval process, Cronus Pharma demonstrated that its generic robenacoxib injection is bioequivalent to brand-name Onsior injection.

Bioequivalence Study Protocols and Pharmacokinetic Metrics

Under the FDA's abbreviated new animal drug application (ANADA) pathway, a generic injectable must demonstrate bioequivalence to the reference listed drug (Elanco's Onsior injection, NADA 141-443). The standard framework uses crossover pharmacokinetic studies in the target species, comparing the rate and extent of drug absorption:

• Key Parameters Measured:
  • Cmax (peak concentration): The maximum blood concentration achieved.
  • AUC (area under the curve), e.g. AUC(0–t) and AUC(0–∞): The total systemic exposure over time.
  • Tmax (time to peak): The time required to reach maximum blood concentration.
• Statistical Acceptance Criteria: FDA requires the 90% confidence intervals for the geometric mean ratio of the generic to the reference drug to fall within the 80% to 125% range for Cmax and AUC. The approval of ANADA 200-804 confirms Cronus Pharma's generic met these criteria.
• Formulation Specifics:
  • Concentration: The generic is a 20 mg/mL sterile injectable solution of robenacoxib, matching the Onsior injection strength.
  • Route of Administration: Approved for subcutaneous (SC) injection.
  • Indication and Dose: It shares the same dose (2 mg/kg once daily for up to 3 days) and the same species-specific surgical indications as the brand.

Tissue-Level Bio-distribution

While systemic bioequivalence is measured via blood plasma, robenacoxib's therapeutic success relies on its unique distribution characteristics:

1. High Protein Binding: Robenacoxib is highly bound to plasma proteins (exceeding 98% in both dogs and cats). This keeps the vast majority of the drug within the vascular compartment during initial circulation.
2. Inflammatory Exudate Penetration: Due to its chemical structure, the molecule has a high affinity for the acidic, protein-rich exudates that accumulate at surgical sites. It easily exits the blood vessels at the site of trauma and binds to cyclooxygenase enzymes locally.
3. Organ-Sparing Elimination: Because it clears from the general circulation in 1 to 2 hours, it minimizes the duration of COX-1 inhibition in healthy tissues. The kidneys, liver, and stomach lining are exposed to only minimal active drug, reducing systemic toxicity risks while the site of incision receives targeted, long-lasting anti-inflammatory coverage for 24 hours.

For veterinary practices, the availability of a generic injectable lowers the cost of surgical preparation and in-clinic pain management, allowing clinics to incorporate modern COX-2 selective NSAID therapy into standard anesthetic protocols more affordably.

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Dog vs. Cat Labels: Surgeries, Age, and Route

Although robenacoxib injection is approved for both dogs and cats, the FDA labels carry distinct, non-interchangeable parameters depending on the species.

Parameter	Canine Label (Dogs)	Feline Label (Cats)
Approved Surgeries	Soft tissue surgery (e.g., ovariohysterectomy, castration, lumpectomy, abdominal procedures)	Orthopedic surgery, ovariohysterectomy (spay), and castration (neuter)
Minimum Age	4 months (16 weeks)	4 months (16 weeks)
Minimum Weight	5.5 lbs (2.5 kg) for oral tablets; no weight limit for SC injection	5.5 lbs (2.5 kg) for oral tablets; no weight limit for SC injection
Route of Administration	Subcutaneous (SC) injection only	Subcutaneous (SC) injection only
Standard Dose	2 mg/kg (0.91 mg/lb) once daily	2 mg/kg (0.91 mg/lb) once daily
Maximum Duration	3 days (72 hours) cumulative	3 days (72 hours) cumulative

Specific Surgery Approvals

• In Dogs: Robenacoxib injection is indicated strictly for the control of postoperative pain and inflammation associated with soft tissue surgery. It is not labeled for orthopedic surgeries (such as TPLO or fracture repair) in dogs, though veterinarians may use it off-label for these indications based on clinical judgment.
• In Cats: The feline label is broader, covering postoperative pain associated with orthopedic surgery, ovariohysterectomy, and castration. This wide indication reflects the drug's role in feline surgery, where safe pain options are limited.

Age Restrictions

Both labels require patients to be at least 4 months of age. Safety has not been established in younger puppies or kittens, whose renal and hepatic clearance mechanisms are still developing.

In-Clinic Administration: Timing the Injection

Because the injection is a clinic-administered dose, when it is given matters as much as whether it is given:

• Dogs: The injection is typically administered subcutaneously about 45 minutes before the start of surgery, alongside the pre-anesthetic medication, so that anti-inflammatory drug levels are established at the site of incision by the time tissue trauma occurs. Subsequent doses (if needed) are then either repeated as SC injection in hospital or transitioned to the oral tablet for the owner to give at home.
• Cats: The injection is given at the time of surgery (perioperatively). Owners are then sent home with one to two oral tablets to complete a total course of no more than three daily doses.
• The hand-off rule: The first in-clinic injection counts as Day 1. If the veterinarian sends home tablets, they are for Day 2 and (at most) Day 3 — never a full three-day bottle on top of the injection.

Getting this timing right is what keeps a patient inside the 3-day safety ceiling, which is the single most important constraint on the drug.

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The 3-Day Maximum Rule and Clinical Transition

The single most critical safety boundary for robenacoxib injection is the 3-day maximum duration limit.

The drug is labeled for a maximum of 3 consecutive daily doses. "Safety has not been demonstrated for usage longer than 3 days" is a prominent warning on both the brand and generic labels.

Cumulative Dosing Across Formulations

In clinical practice, veterinarians often transition a patient from an injectable NSAID administered in-clinic to oral tablets sent home with the owner.

[!IMPORTANT] The 3-Day Rule is Cumulative: The 3-day (72-hour) limit applies to the entire course of therapy, regardless of the formulation.

• If a cat receives a robenacoxib injection (2 mg/kg SC) at the clinic on the day of surgery (Day 1), the owner can administer a maximum of two oral tablets (one tablet once daily on Day 2 and Day 3).
• Do not administer an injection on Day 1, and then send home a 3-day supply of oral tablets. This results in a 4-day course, violating the FDA safety ceiling.
• Never administer the injection and oral tablets concurrently.

Why the 3-Day Limit is Non-Negotiable

The 3-day ceiling reflects what the safety data support, not an arbitrary convenience:

• In Dogs: A month-long laboratory safety study and foreign post-marketing experience linked longer robenacoxib exposure to elevated liver enzymes, hepatopathy, and — in a small number of dogs — hepatic necrosis and death. The short, three-day course is where the canine safety data are strongest.
• In Cats: Cats have limited capacity to clear many drugs through glucuronidation, and no NSAID is approved for long-term use in cats in the U.S. Robenacoxib's COX-2 selectivity supports its short-term feline safety profile, but safety beyond three doses has not been established — which is why a cat goes home with two or three tablets, never a refillable bottle.

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Feline Postoperative Analgesia: Robenacoxib vs. Meloxicam

Historically, the primary injectable NSAID used for feline surgeries in the United States was meloxicam (Metacam). Understanding the differences between these two drugs is essential for choosing the right protocol; see our meloxicam for dogs guide for the meloxicam label in detail.

Feature	Robenacoxib Injection (Onsior / Generic)	Meloxicam Injection (Metacam)
COX Selectivity	Highly COX-2 selective	COX-2 selective (relative)
Feline Duration	Up to 3 days (once daily SC or oral)	Single dose only (SC injection)
FDA Black Box Warning	None	Yes (Warning against repeated dosing in cats)
Cat Safety Profile	High safety margin for 3 days; low renal risk in hydrated patients	Repeated dosing in cats has caused acute renal failure and death
In-Clinic Route	Subcutaneous (SC)	Subcutaneous (SC) or Intravenous (IV)

The Feline Meloxicam Boxed Warning

In 2010, the FDA required a boxed warning to be added to all feline meloxicam labels. The warning states that repeated use of meloxicam in cats has been associated with acute renal failure and death. While meloxicam is highly effective as a single, one-time injection administered prior to surgery, sending it home as an oral liquid for continued feline pain management carries a high risk of severe kidney damage.

The Robenacoxib Advantage

Robenacoxib provides a safer therapeutic window. Because of its high COX-2 selectivity and rapid blood clearance, felines can receive it for three consecutive days without the elevated risk of acute renal failure associated with meloxicam. This allows veterinarians to send home effective oral pain relief (via generic or Onsior tablets) for the critical 48 hours following surgery, supporting smoother postoperative recoveries.

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openFDA Adverse Event Data: Species Split and Analysis

To evaluate how robenacoxib performs in the field, we analyzed the openFDA Animal Adverse Event Database (data snapshot current through June 2026). Counts below are unique reports (one count per distinct report, deduplicated on the FDA report identifier) in which robenacoxib was listed as an active ingredient. Like all passive-surveillance data, these are raw report counts, not rates or proof of causality. For the class-level context, see our veterinary NSAID adverse-event data overview.

The database contains 3,520 unique reports where robenacoxib (Onsior) was listed as an active ingredient.

The Feline-Dominant Reporting Split

A review of the report metadata reveals a striking species distribution:

• Cat Reports: 3,064 (87.0% of total reports)
• Dog Reports: 110 (3.1% of total reports)
• No Species Listed / Other: 346 (9.8% of total reports)

This massive split is not due to robenacoxib being inherently more dangerous to cats. Rather, it reflects prescribing patterns. In dogs, veterinarians have access to a wide array of long-term oral NSAIDs (such as carprofen, meloxicam, deracoxib, firocoxib, and grapiprant), meaning robenacoxib is rarely the first choice for canine pain. In cats, however, robenacoxib is the dominant take-home NSAID, leading to a much larger feline exposure base.

Top 10 Reported Clinical Reactions for Robenacoxib

1. Lethargy / depression: 407 reports
2. Not eating (inappetence): 380 reports
3. Lack of efficacy - NOS: 307 reports
4. Anorexia: 303 reports
5. Fever (pyrexia): 293 reports
6. Vomiting: 286 reports
7. Death by euthanasia: 283 reports
8. Behavioral disorder NOS (agitation/vocalization): 276 reports
9. Other abnormal laboratory test results: 267 reports
10. Death: 231 reports

Understanding the Safety Signals

• Lethargy, Anorexia, and Vomiting: These represent standard veterinary NSAID adverse reactions. Because NSAIDs can affect gastrointestinal perfusion, mild nausea, decreased appetite, and quietness are common early warning signs. Owners should be instructed to discontinue the drug and call the clinic if these signs develop.
• Death by Euthanasia: In passive surveillance databases, "death" and "euthanasia" are frequently reported outcomes because owners and vets are more likely to submit reports for severe cases. In many of these reports, the patient had underlying, undiagnosed renal disease or received a concurrent medication (such as a steroid) that triggered a crisis.
• Renal Signals: Elevated creatinine and blood urea nitrogen (BUN) appear in the laboratory findings category, highlighting the potential for renal decompensation, particularly in older felines or patients that experience hypotension during anesthesia.

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Patient Selection and Veterinary Guidelines

To minimize risks, veterinary teams should implement a strict pre-surgical checklist before administering robenacoxib injection:

1. Patient Selection Criteria

• Hydration is Mandatory: Do not administer robenacoxib to dehydrated animals, patients with pre-existing cardiovascular instability, or those experiencing active shock.
• Renal Function Baseline: Perform pre-anesthetic bloodwork (BUN, creatinine, and urine specific gravity) in all patients, particularly senior cats (older than 7 years) and dogs with histories of renal disease.
• Blood Pressure Management: Ensure the patient maintains adequate blood pressure (Mean Arterial Pressure >60 mmHg) during anesthesia, as intraoperative hypotension combined with NSAID administration can compromise renal blood flow.

2. Medication Washout Boundaries

Concurrent administration of robenacoxib with other inflammatory or immunomodulatory drugs is contraindicated due to the risk of severe gastrointestinal ulceration and renal damage.

[!CAUTION] Medication Washout Is Required: The label calls for an appropriate washout period when switching from another NSAID or from a corticosteroid to robenacoxib (and vice versa).

• Other NSAIDs (carprofen, meloxicam, firocoxib, aspirin, etc.): Do not overlap. Tell the veterinarian about every NSAID or aspirin given in the prior days to weeks so the washout is planned correctly.
• Corticosteroids (prednisolone, dexamethasone, etc.): Do not give a "pre-op" steroid and a "post-op" robenacoxib injection together; overlapping an NSAID with a steroid markedly raises the risk of GI ulceration.
• The exact interval is a clinical decision based on the specific drugs, dose, and patient — follow the veterinarian's direction and the label.

3. Monitoring Guidelines

Instruct owners to monitor for the "Big Four" clinical warnings at home:

1. Appetite Changes: The pet stops eating or eats significantly less.
2. Gastrointestinal Distress: Vomiting or diarrhea (especially if dark, tarry stools are observed).
3. Energy Levels: Severe lethargy, depression, or refusal to move.
4. Urination Patterns: Increased drinking or changes in urination frequency.

If any of these signs occur, the owner must stop the medication immediately and contact the veterinary clinic.

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Frequently Asked Questions

Can robenacoxib injection be used for more than 3 days?

No. The FDA-approved label restricts use to a maximum of 3 consecutive days. Safety beyond three days has not been established; longer canine exposure has been linked to hepatopathy, and no NSAID is approved for long-term use in cats in the U.S.

What is the difference between Onsior tablets and Onsior injection?

The active ingredient (robenacoxib) is identical. The injection is a 20 mg/mL sterile solution administered subcutaneously in the clinic, typically as a pre-anesthetic or intraoperative treatment. The tablets are flavored oral medications designed for once-daily take-home use. They must be transitioned carefully to ensure the 3-day cumulative limit is not exceeded.

Can robenacoxib injection be given to dogs and cats with kidney disease?

It is contraindicated in patients with pre-existing, unstable renal insufficiency. For patients with stable, early-stage chronic kidney disease (IRIS Stage 1 or 2 cats), veterinarians may choose to use it in-clinic if the benefits of surgical pain control outweigh the risks, but the patient must remain fully hydrated and blood pressure monitored throughout the procedure.

How quickly does a robenacoxib injection start working?

Subcutaneously administered robenacoxib is absorbed rapidly. Peak plasma concentrations are reached in approximately 1 hour in dogs and cats. Because it binds tightly to inflamed tissues, its clinical analgesic effect begins before the patient wakes from anesthesia.

What should be done in cases of accidental robenacoxib overdose?

In clinical settings, a subcutaneous injection overdose is managed supportively. If a patient is accidentally administered an excessive dose, the veterinary team should immediately initiate intravenous fluid therapy to support renal perfusion and prevent hypotension. Gastrointestinal protectants, such as misoprostol (a synthetic prostaglandin analog) and proton pump inhibitors (like omeprazole), should be administered to protect the stomach lining. Because robenacoxib is highly protein-bound, hemodialysis is ineffective at clearing the drug, and therapy must focus on protecting the target organs (kidneys and gut) until systemic elimination is complete.

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Sources

• FDA Center for Veterinary Medicine — FDA Approves First Generic Robenacoxib Injectable for Postoperative Pain and Inflammation in Dogs and Cats (March 9, 2026): https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-first-generic-robenacoxib-injectable-postoperative-pain-and-inflammation-dogs-and-cats
• FDA Center for Veterinary Medicine — Freedom of Information (FOI) Summary for ANADA 200-804 (ROBENACOXIB INJECTION, approved March 9, 2026): https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/17381
• DailyMed — ONSIOR (robenacoxib) injection label (Elanco US Inc.): https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=f4f307a0-88b5-4740-b198-35edef954bf1
• FDA Center for Veterinary Medicine — What Veterinarians Should Advise Clients About Pain Control and NSAIDs in Dogs and Cats: https://www.fda.gov/animal-veterinary/resources-you/what-veterinarians-should-advise-clients-about-pain-control-and-nonsteroidal-anti-inflammatory-drugs
• dvm360 — First generic robenacoxib injectable is FDA-approved for postoperative use in dogs and cats: https://www.dvm360.com/view/first-generic-robenacoxib-injectable-is-fda-approved-for-postoperative-use-in-dogs-and-cats
• openFDA — Animal and Veterinary Adverse Event Reports Dataset (Queries for active ingredients: robenacoxib, run date June 26, 2026): https://open.fda.gov/apis/animalandveterinary/event/