For the relief of pain and inflammation associated with

osteoarthritis in dogs and for the control of postoperative pain associated with soft

tissue and orthopedic surgeries in dogs.

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 specificity

an in vitro study using canine cell cultures, carprofen demonstrated selective inhibitionof COX-2 versus COX-1.

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

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)

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.

Comparison of a single 25 mg dose in Beagle dogs after subcutaneous and oral

administration demonstrated that the dorsoscapular subcutaneous administration

results in a slower rate of drug input (as reflected by mean peak observed concentrations)

but comparable total drug absorption within a 12 hour dosing interval (as

reflected by area under the curve from hours zero to 12 postdose).

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.

Novox Caplets are indicated for the relief of pain and inflammation associated with

osteoarthritis in dogs and for the control of postoperative pain associated with soft

tissue and orthopedic surgeries in dogs.

Always provide Client Information Sheet with prescription. 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 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. Novox

Caplets 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. Novox Caplets should be given by mouth and may be given

with or without food. Care should be taken to ensure that the dog consumes the

complete dose.

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 7 placebocontrolled,

masked studies examining the anti-inflammatory and analgesic effectiveness

of carprofen in various breeds of dogs.

Separate placebo-controlled, masked, multicenter field studies confirmed the antiinflammatory

and analgesic effectiveness of carprofen 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

N

Cl

O

OH

H

CH3

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.

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 final 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 caplets). 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 caplets 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 pretreatment

values for dogs receiving carprofen caplets 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

caplets 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 hematopoetic, 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 caplets 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.

Novox Caplets should not be used in dogs exhibiting previous hypersensitivity to

carprofen.

As a class, cyclooxygenase inhibitory NSAIDs may be associated with gastrointestinal

and renal toxicity. Effects may result from decreased prostaglandin production

and inhibition of the enzyme cyclooxygenase which is responsible for the

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

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

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. Since many NSAIDs possess the potential to induce gastrointestinal

ulceration, concomitant use of carprofen with other anti-inflammatory drugs, such

as corticosteroids and NSAIDs, should be avoided or very closely monitored.

Sensitivity to drug-associated adverse reactions varies with the individual patient.

For example, carprofen treatment was not associated with renal toxicity or gastrointestinal

ulceration in well-controlled safety studies of up to ten times the dose in dogs.

Carprofen 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 carprofen in animals less than 6 weeks of age, in pregnant

dogs, dogs used for breeding purposes, or in lactating bitches has not been established.

Safety has not been established for IV or IM administration. Studies to

determine the activity of caprofen 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

injections. If additional pain medication is warranted after administration of the

total daily dose of carprofen, alternative analgesia should be considered. The use

of another NSAID is not recommended.

Novox Caplets should be stored out of reach of dogs in a secured location. Severe

adverse reactions may occur if large quantities of caplets are ingested. If you suspect

your dog has consumed Novox Caplets above the labeled dose, please call your

veterinarian for immediate assistance and notify VEDCO, Inc. at 1-888-708-3326.

Carprofen, 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.

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.

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

During investigational studies with an oral carprofen formulation at 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.

Inappetence                   1.6                                         1.5

Vomiting                          3.1                                          3.8

Diarrhea/Soft stool      3.1                                          4.5

Behavior change           0.8                                           0.8

Dermatitis                      0.8                                            0.8

PU/PD                              0.8                                             -

SAP increase                  7.8                                           8.3

ALT increase                   5.4                                           4.5

AST increase                  2.3                                            0.8

BUN increase                 3.1                                             1.5

Bilirubinuria                 16.3                                            12.1

Ketonuria                     14.7                                             9.1

Clinical pathology parameters listed represent reports of increases from pre-treatment

values; medical judgment is necessary to determine clinical relevance.

During investigational studies of surgical pain for the caplet formulation, no clinically

Neurologic: Ataxia, paresis, paralysis, seizures, vestibular signs, disorientation.

Behavorial: Sedation, lethargy, hyperactivity, restlessness, aggressiveness.

Immunologic or hypersensitivity: Facial swelling, hives, erythema.

In rare situations, death has been associated with some of the adverse reactions

listed above.

To report a suspected adverse reaction call 1-888-708-3326.

Store tablets at controlled room temperature 15°-30°C (59°-86°F).

Novox Caplets 25 mg-Each light orange, convex tablet debossed with “G” on one

side and bisected on the other side with “33” on the left and “11” on the right of

the bisect.

Bottles of 60 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NDC 50989-740-50

Bottles of 100 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NDC 50989-740-51

Bottles of 180 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NDC 50989-740-84

Novox Caplets 75 mg-Each light orange, convex tablet debossed with “G” on one

side and bisected on the other side with “33” on the left and “22” on the right of

the bisect.

Bottles of 60 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NDC 50989-741-50

Bottles of 180 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NDC 50989-741-84

Novox Caplets 100 mg-Each light orange, convex tablet debossed with “G” on one

side and bisected on the other side with “33” on the left and “33” on the right of

the bisect.

Bottles of 60 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NDC 50989-742-50

Bottles of 180 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .NDC 50989-742-84

Anti-Inflammatory Drugs, Rainsford KD, ed. CRC Press, Boca Raton, p. 33, 1986.

inducible cyclooxygenase activity in human platelets and mononuclear cells by

4. Ricketts AP, Lundy KM, Seibel SB: Evaluation of selective inhibition of canine

cyclooxygenase 1 and 2 by carprofen and other nonsteroidal anti-inflammatory

5. Ceuppens JL, et al: Non-steroidal anti-inflammatory agents inhibit the synthesisof IgM rheumatoid factor

6. Ceuppens JL, et al: Endogenous prostaglandin E2 enhances polyclonalimmunoglobulin production by ionically inhibiting T suppressor cell activity.

immune response. Immunopharmacology 3:205, 1981.8. Leung KH,

Possible roles of the products of cyclooxygenase and lipoxygenase pathways of

9. Veit BC: Immunoregulatory activity of cultured-induced suppressor

10. Schmitt M, et al: Biopharmaceutical evaluation of carprofen following singleintravenous, oral, and rectal doses in dogs.

1990.

11. Kore AM: Toxicology of nonsteriodal anti-inflammatory drugs. Veterinary

12. Binns SH: Pathogenesis and pathophysiology of ischemic injury in cases of

13. Boothe DM: Prostaglandins: Physiology and clinical implications. Compendfor Cont Ed

14. Rubin SI: Nonsteroidal anti-inflammatory drugs, prostaglandins, and the kidney.

15. Ko CH, Lange DN, Mandsager RE, et al: Effects of butorphanol and carprofen

1028, 2000.

To report a suspected adverse reaction call VEDCO, Inc. at 1-888-708-3326.

ANADA #200-366, Approved by FDA

Mfg. by:

IMPAX Laboratories, Inc.

Hayward, CA 94544

Dist. by:

Vedco, Inc.

St. Joseph, MO 64507

Rev. 09/2005

512-02