How to Order Prescriptions
Description
Carprovet is a non-steroidal anti-inflammatory drug (NSAID) that is used to
reduce pain and inflammation (soreness) due to osteoarthritis and pain
following surgery in dogs. Carprovet is a prescription drug for dogs. It is
available as a chewable tablet and is given to dogs by mouth. Carprovet (carprofen) is a non-steroidal anti-inflammatory drug (NSAID) of the propionic acid class that includes ibuprofen, naproxen,
and ketoprofen. Carprofen is the nonproprietary designation for a substituted carbazole, 6-chloro-α-methyl-9H-carbazole-2-acetic acid. The empirical formula is C15H12ClNO2 and the molecular weight 273.72.
Caution
Federal law restricts this drug to use by or on the order of a licensed veterinarian.
Clinical Pharmacology
Carprofen is a non-narcotic, non-steroidal anti-inflammatory agent with characteristic analgesic and antipyretic activity
approximately equipotent to indomethacin in animal models.1 The mechanism of action of carprofen, like that of other NSAIDs, is believed to be
associated with the inhibition of cyclooxygenase activity. Two unique cyclooxygenases have been described in mammals.2
The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function. The inducible
cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-1 is thought to be associated with gastrointestinal and
renal toxicity while inhibition of COX-2 provides anti-inflammatory activity. The specialty of a particular NSAID for COX-2 versus COX-1 may vary from
species to species.3
In an in vitro study using canine cell cultures, carprofen demonstrated selective inhibition of COX-2 versus COX-1.4
Clinical relevance of these data has not been shown. Carprofen has also been shown to inhibit the release of several prostaglandins in two inflammatory cell
systems: rat polymorphonuclear leukocytes (PMN) and human rheumatoid synovial cells, indicating inhibition of acute (PMN system) and chronic
(synovial cell system) inflammatory reactions.1 Several studies have demonstrated that carprofen has modulatory effects on both humoral and cellular
immune responses.5-9 Data also indicate that carprofen inhibits the production of osteoclast-activating factor (OAF), PGE1, and PGE2 by its inhibitory
effect in prostaglandin biosynthesis.1 Based upon comparison with data obtained from intravenous administration, carprofen is rapidly and nearly
completely absorbed (more than 90% bioavailable) when administered orally.10 Peak blood plasma concentrations are achieved in 1-3 hours after oral
administration of 1, 5, and 25 mg/kg to dogs. The mean terminal half-life of carprofen is approximately 8 hours (range 4.5-9.8 hours) after single oral
doses varying from 1-35 mg/kg of body weight. After a 100 mg single intravenous bolus dose, the mean elimination half-life was approximately
11.7 hours in the dog. Carprofen is more than 99% bound to plasma protein and exhibits a very small volume of distribution. Carprofen is eliminated in
the dog primarily by biotransformation in the liver followed by rapid excretion of the resulting metabolites (the ester glucuronide of carprofen and the
ether glucuronides of 2 phenolic metabolites, 7-hydroxy carprofen and 8-hydroxy carprofen) in the feces (70-80%) and urine (10-20%). Some
enterohepatic circulation of the drug is observed.
Indications
Carprovet is indicated for the relief of pain and inflammation associated with osteoarthritis and for the control of postoperative pain
associated with soft tissue and orthopedic surgeries in dogs.
Contraindications
Carprovet should not be used in dogs exhibiting previous hypersensitivity to carprofen.
Warnings
Keep out of reach of children. Not for human use. Consult a physician in cases of accidental ingestion by humans.
For use in dogs only. Do not use in cats. All dogs should undergo a thorough history and physical examination before initiation of NSAID therapy.
Appropriate laboratory tests to establish hematological and serum biochemical baseline data prior to, and periodically during, administration of any
NSAID should be considered. Owners should be advised to observe for signs of potential drug toxicity (see INFORMATION FOR DOG OWNERS, ADVERSE REACTIONS, ANIMAL SAFETY and Post-Approval Experience).
Precautions
As a class, cyclooxygenase inhibitory NSAIDs may be associated with gastrointestinal, renal and hepatic toxicity. Effects may result from
decreased prostaglandin production and inhibition of the enzyme cyclooxygenase which is responsible for the formation of prostaglandins from
arachidonic acid. 11-14 When NSAIDs inhibit prostaglandins that cause inflammation they may also inhibit those prostaglandins which maintain normal
homeostatic function. These anti-prostaglandin effects may result in clinically significant disease in patients with underlying or pre-existing disease
more often than in healthy patients.12,14 NSAID therapy could unmask occult disease which has previously been undiagnosed due to the absence of
apparent clinical signs. Patients with underlying renal disease for example, may experience exacerbation or decompensation of their renal disease while
on NSAID therapy.11-14 The use of parenteral fluids during surgery should be considered to reduce the potential risk of renal complications when using
NSAIDs perioperatively. Carprofen is an NSAID, and as with others in that class, adverse reactions may occur with its use. The most frequently reported
effects have been gastrointestinal signs. Events involving suspected renal, hematologic, neurologic, dermatologic, and hepatic effects have also been
reported. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with renal, cardiovascular,
and/or hepatic dysfunction. Concurrent administration of potentially nephrotoxic drugs should be approached cautiously, with appropriate monitoring.
Concomitant use of Carprovet with other anti-inammatory drugs, such as other NSAIDs or corticosteroids, should be avoided because of the potential
increase of adverse reactions, including gastrointestinal ulcerations and/or perforations. Sensitivity to drug-associated adverse reactions varies with the
individual patient. Dogs that have experienced adverse reactions from one NSAID may experience adverse reactions from another NSAID. Carprofen
treatment was not associated with renal toxicity or gastrointestinal ulceration in well-controlled safety studies of up to ten times the dose in healthy
dogs. Carprovet is not recommended for use in dogs with bleeding disorders (e.g., Von Willebrand’s disease), as safety has not been established in dogs
with these disorders. The safe use of Carprovet in animals less than 6 weeks of age, pregnant dogs, dogs used for breeding purposes, or in lactating
bitches has not been established. Studies to determine the activity of Carprovet 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. Such drugs
commonly used include cardiac, anticonvulsant and behavioral medications. It has been suggested that treatment with carprofen may reduce the level
of inhalant anesthetics needed.15
If additional pain medication is warranted after administration of the total daily dose of Carprovet, alternative analgesia should be considered. The use of
another NSAID is not recommended. Consider appropriate washout times when switching from one NSAID to another or when switching from
corticosteroids use to NSAID use. Store out of reach of dogs in a secured location. Severe adverse reactions may occur if large quantities of tablets are
ingested. If you suspect your dog has consumed Carprovet chewable tablets above the labeled dose, please call your veterinarian for immediate
assistance and notify Dechra at (866) 933-2472.
Information for Dog Owners
Carprovet, like other drugs of its class, is not free from adverse reactions. Owners should be advised of the potential
for adverse reactions and be informed of the clinical signs associated with drug intolerance. Adverse reactions may include decreased appetite,
vomiting, diarrhea, dark or tarry stools, increased water consumption, increased urination, pale gums due to anemia, yellowing of gums, skin or white of
the eye due to jaundice, lethargy, incoordination, seizure, or behavioral changes. Serious adverse reactions associated with this drug class can
occur without warning and in rare situations result in death (see ADVERSE REACTIONS). Owners should be advised to discontinue Carprovet
therapy and contact their veterinarian immediately if signs of 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. Owners should be
advised of the importance of periodic follow up for all dogs during administration of any NSAID.
Adverse Reactions
During investigational studies for the caplet formulation with twice daily administration of 1 mg/lb, no clinically significant
adverse reactions were reported. Some clinical signs were observed during field studies (n=297) which were similar for carprofen caplet- and
placebo-treated dogs. Incidences of the following were observed in both groups: vomiting (4%), diarrhea (4%), changes in appetite (3%), lethargy
(1.4%), behavioral changes (1%), and constipation (0.3%). The product vehicle served as control.
There were no serious adverse events reported during clinical field studies with once daily administration of 2 mg/lb.
The following categories of abnormal health observations were reported. The product vehicle served as control.
Post-Approval Experience
Although not all adverse reactions are reported, the following adverse reactions are based on voluntary post-approval adverse drug experience
reporting. The categories of adverse reactions are listed in decreasing order of frequency by body system.
Gastrointestinal: Vomiting, diarrhea, constipation, inappetence, melena, hematemesis, gastrointestinal ulceration, gastrointestinal bleeding, pancreatitis.
Hepatic
Inappetence, vomiting, jaundice, acute hepatic toxicity, hepatic enzyme elevation, abnormal liver function test(s), hyperbilirubinemia,
bilirubinuria, hypoalbuminemia. Approximately one-fourth of hepatic reports were in Labrador Retrievers.
Neurologic
Ataxia, paresis, paralysis, seizures, vestibular signs, disorientation.
Urinary
Hematuria, polyuria, polydipsia, urinary incontinence, urinary tract infection, azotemia, acute renal failure, tubular abnormalities including acute
tubular necrosis, renal tubular acidosis, glucosuria.
Behavioral: Sedation, lethargy, hyperactivity, restlessness, aggressiveness.
Hematologic
Immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, blood loss anemia, epistaxis.
Dermatologic: Pruritus, increased shedding, alopecia, pyotraumatic moist dermatitis (hot spots), necrotizing panniculitis/vasculitis, ventral ecchymosis.
Immunologic or hypersensitivity
Facial swelling, hives, erythema.
In rare situations, death has been associated with some of the adverse reactions listed above.
To report suspected adverse events, for technical assistance or to obtain a copy of the safety data sheet (SDS), contact Dechra at (866) 933-2472.
For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS, or www.fda.gov/reportanimalae
Dosage and Administration
Always provide Client Information Sheet with prescription. Carefully consider the potential benefits and risk of
Carprovet and other treatment options before deciding to use Carprovet. Use the lowest effective dose for the shortest duration consistent with
individual response. The recommended dosage for oral administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be
administered as 2 mg/lb (4.4 mg/kg) of body weight once daily or divided and administered as 1 mg/lb (2.2 mg/kg) twice daily. For the control of
postoperative pain, administer approximately 2 hours before the procedure. Carprovet chewable tablets are scored and dosage should be calculated in
half-tablet increments. Tablets can be halved by placing the tablet on a hard surface and pressing down on both sides of the score. Carprovet chewable
tablets may be fed by hand or placed on food. Care should be taken to ensure that the dog consumes the complete dose.
Effectiveness
Confirmation of the effectiveness of carprofen for the relief of pain and inflammation associated with osteoarthritis, and for the control
of postoperative pain associated with soft tissue and orthopedic surgeries, was demonstrated in 5 placebo-controlled, masked studies examining the
anti-inflammatory and analgesic effectiveness of carprofen caplets in various breeds of dogs.
Separate placebo-controlled, masked, multicenter field studies confirmed the anti-inflammatory and analgesic effectiveness of carprofen caplets when
dosed at 2 mg/lb once daily or when divided and administered at 1 mg/lb twice daily. In these 2 field studies, dogs diagnosed with osteoarthritis
showed statistically significant overall improvement based on lameness evaluations by the veterinarian and owner observations when administered
carprofen at labeled doses.
Separate placebo-controlled, masked, multicenter field studies confirmed the effectiveness of carprofen caplets for the control of postoperative pain
when dosed at 2 mg/lb once daily in various breeds of dogs. In these studies, dogs presented for ovariohysterectomy, cruciate repair and aural surgeries
were administered carprofen preoperatively and for a maximum of 3 days (soft tissue) or 4 days (orthopedic) postoperatively.
In general, dogs administered carprofen showed statistically significant reduction in pain scores compared to controls.
Animal Safety
Laboratory studies in unanesthetized dogs and clinical field studies have demonstrated that carprofen is well tolerated in dogs after oral administration.
In target animal safety studies, carprofen was administered orally to healthy Beagle dogs at 1, 3, and 5 mg/lb twice daily (1, 3 and 5 times the
recommended total daily dose) for 42 consecutive days with no significant adverse reactions. Serum albumin for a single female dog receiving 5 mg/lb
twice daily decreased to 2.1 g/dL after 2 weeks of treatment, returned to the pre-treatment value (2.6 g/dL) after 4 weeks of treatment, and was 2.3
g/dL at the intinal 6-week evaluation. Over the 6-week treatment period, black or bloody stools were observed in 1 dog (1 incident) treated with 1 mg/lb
twice daily and in 1 dog (2 incidents) treated with 3 mg/lb twice daily. Redness of the colonic mucosa was observed in 1 male that received 3 mg/lb
twice daily.
Two of 8 dogs receiving 10 mg/lb orally twice daily (10 times the recommended total daily dose) for 14 days exhibited hypoalbuminemia. The mean
albumin level in the dogs receiving this dose was lower (2.38 g/dL) than each of 2 placebo control groups (2.88 and 2.93 g/dL, respectively). Three
incidents of black or bloody stool were observed in 1 dog. Five of 8 dogs exhibited reddened areas of duodenal mucosa on gross pathologic
examination. Histologic exam of these areas revealed no evidence of ulceration, but did show minimal congestion of the lamina propria in 2 of the
5 dogs. In separate safety studies lasting 13 and 52 weeks, respectively, dogs were administered orally up to 11.4 mg/lb/day (5.7 times the
recommended total daily dose of 2 mg/lb) of carprofen. In both studies, the drug was well tolerated clinically by all of the animals. No gross or histologic
changes were seen in any of the treated animals. In both studies, dogs receiving the highest doses had average increases in serum L-alanine
aminotransferase (ALT) of approximately 20 IU.
In the 52-week study, minor dermatologic changes occurred in dogs in each of the treatment groups but not in the control dogs. The changes were
described as slight redness or rash and were diagnosed as non-specific dermatitis. The possibility exists that these mild lesions were treatment related,
but no dose relationship was observed.
Clinical field studies were conducted with 549 dogs of different breeds at the recommended oral doses for 14 days (297 dogs were included in a study
evaluating 1 mg/lb twice daily and 252 dogs were included in a separate study evaluating 2 mg/lb once daily). In both studies the drug was clinically
well tolerated and the incidence of clinical adverse reactions for carprofen-treated animals was no higher than placebo-treated animals (placebo
contained inactive ingredients found in carprofen). For animals receiving 1 mg/lb twice daily, the mean post-treatment serum ALT values were 11 IU
greater and 9 IU less than pre-treatment values for dogs receiving carprofen and placebo, respectively. Differences were not statistically significant.
For animals receiving 2 mg/lb once daily, the mean post-treatment serum ALT values were 4.5 IU greater and 0.9 IU less than pre-treatment values for
dogs receiving carprofen and placebo, respectively. In the latter study, 3 carprofen-treated dogs developed a 3-fold or greater increase in (ALT) and/or
(AST) during the course of therapy. One placebo-treated dog had a greater than 2-fold increase in ALT. None of these animals showed clinical signs
associated with laboratory value changes. Changes in the clinical laboratory values (hematology and clinical chemistry) were not considered clinically
significant. The 1 mg/lb twice daily course of therapy was repeated as needed at 2-week intervals in 244 dogs, some for as long as 5 years.
Clinical field studies were conducted in 297 dogs of different breeds undergoing orthopedic or soft tissue surgery. Dogs were administered 2 mg/lb of
carprofen two hours prior to surgery then once daily, as needed for 2 days (soft tissue surgery) or 3 days (orthopedic surgery). Carprofen was well
tolerated when used in conjunction with a variety of anesthetic-related drugs. The type and severity of abnormal health observation in carprofen- and
placebo-treated animals were approximately equal and few in number (see ADVERSE REACTIONS). The most frequent abnormal health observation was
vomiting and was observed at approximately the same frequency in carprofen- and placebo-treated animals. Changes in clinicopathologic indices of
hematopoietic, renal, hepatic, and clotting function were not clinically significant. The mean post-treatment serum ALT values were 7.3 IU and 2.5 IU
less than pre-treatment values for dogs receiving carprofen and placebo, respectively.
The mean post-treatment AST values were 3.1 IU less for dogs receiving carprofen and 0.2 IU greater for dogs receiving placebo.
Storage
Store at controlled room temperature 20°-25° C (68°-77° F) with excursions between 15°-30°C (59°-86° F) permitted.
How Supplied
Carprovet chewable tablets are scored, and contain 25 mg, 75 mg, or 100 mg of carprofen per tablet. Each tablet size is packaged in
bottles containing 30, 60, or 180 tablets.