Canine Osteoarthritis Brochure

WAGS.
UNLEASHED.
Identifying and Controlling Arthritis in Dogs
What is arthritis?
Arthritis, or osteoarthritis (OA), is a progressive,
degenerative disease that can occur in dogs of
all ages, sizes and breeds. The disease can affect
one or more joints, leading to pain, stiffness, joint
swelling, lameness and reduced mobility — all of
which can decrease a dog’s quality of life.
Because OA is a progressive condition that
manifests over time, the signs of pain become more
apparent as the condition becomes more severe.
What signs of arthritis should
I watch for in my dog?
Unfortunately, dogs can’t tell us where or when it
hurts, so sometimes it can be difficult to know
when a dog is in pain. The key is to look for a
change in your dog’s behavior.
What can I do to help
manage my dog’s arthritis?
Although osteoarthritis is incurable, it can be
managed. By following a few steps, you can
ensure that you and your dog will have many
healthy and happy years together.
Develop a program
The goals of osteoarthritis therapy are to decrease
inflammation and pain, resulting in:
•
Increased activity 1,2
•
Preserved muscle mass and strength
•
Regained function
Medical treatment of osteoarthritis should include:
weight control, exercise, and pharmacological
management of inflammation and pain for an
improved quality of life.3
NSAIDs and other
pharmacologics
Does your dog display any of the following
signs? If so, you might want to talk to
your veterinarian about arthritis.
•
•
•
•
•
•
•
•
•
•
•
•
•
No longer meets you at the door
General decrease in activity or exercise
Reluctance to walk, run, climb, jump or play
Stiffness or decreased movement of joints
Limping or lameness
Difficulty rising from a resting position
Lagging behind on walks
Soreness when touched
Yelping or whimpering in pain
Acting aggressive or withdrawn
Flatness of ears against their head
Licking affected area
Exhibiting other personality changes
Exercise
Weight
Control
If properly treated, the progression of
osteoarthritis can be slowed.4
1 Brown DC et al. Use of activity monitor to detect response to treatment in dogs
with osteoarthritis. JAVMA. 2010;237:66-70.
2 Autefage A, Gossellin J. Efficacy and safety of the long-term oral administration of
carprofen in the treatment of osteoarthritis in dogs. Revue Med Vet. 2007;158:119-127.
3 Johnson SA, Budsberg SC. Non-steroidal anti-inflammatory drugs and
corticosteroids for the management of canine osteoarthritis in dogs.
Vet Clin North Am Small Anim Pract. 1997;27:841-862
4 Litman D. Maximizing success in osteoarthritis care: benefits of a comprehensive
management approach. Int J Rheum. 2008;5:1-37.
Stick with the program
What is RIMADYL?
Medications and therapy may make such a
difference in your dog’s quality of life that you may
be tempted to discontinue treatment. However, an
OA management plan is only effective if your dog
stays on it.
Did you know that human arthritis medications
like aspirin can be toxic to dogs? 1, 2 That’s why
we developed RIMADYL (carprofen).
Long-term treatment provides continuous
improvement in your dog’s mobility and pain
associated with arthritis.1 To ensure that your
dog doesn’t suffer a setback, you’ll need to
keep your dog on your veterinarian’s prescribed
treatment program.
Lighten their load
If needed, reducing your pet’s weight can
significantly decrease the burden on load-bearing
joints. Consult your veterinarian for a weight
management program for your pet.
•
RIMADYL is approved by the FDA for once- or
twice-daily dosing to help manage pain and
inflammation in a dog’s joints
•
RIMADYL was developed specifically for dogs
to help improve their mobility by reducing
joint pain and inflammation
•
RIMADYL was the first anti-inflammatory
medication for osteoarthritis approved for
dogs in the US
•
Over 24 million dogs have been treated with
RIMADYL, making it the #1 osteoarthritis
medication prescribed by veterinarians3, 4
Get their paws moving
Moderate exercise can help strengthen muscles
and reduce the chances of further damage. To
establish an adequate, low-impact routine, consult
your veterinarian.
1 Autefage A, Gossellin J. Efficacy and safety of the long-term oral administration of
carprofen in the treatment of osteoarthritis in dogs. Revue Med Vet. 2007;158:119-127.
IMPORTANT SAFETY INFORMATION: As a class,
NSAIDs may be associated with gastrointestinal,
kidney and liver side effects. These are usually
mild, but may be serious. Pet owners should
discontinue therapy and contact their veterinarian
immediately if side effects occur. Evaluation for
pre-existing conditions and regular monitoring
are recommended for pets on any medication,
including RIMADYL. Use with other NSAIDs or
corticosteroids should be avoided.
1 Kore, A M Toxicology of nonsteroidal anti-inflammatory drugs.
Veterinary Clinics of North America: Small animal practice. 20:419-30; 1990.
2 Jones, R D; Baynes, R E; Nimitz, C T. Nonsteroidal anti-inflammatory
drug toxicosis in dogs and cats: 240 cases (1989-1990). JAVMA, 201:475-7; 1992.
3 VetInsight Analytics, September 2013
4 Data on file. MDI market research, Zoetis Inc.
What kinds of results can
I expect to see from RIMADYL?
While RIMADYL (carprofen) is not a cure for
arthritis, it can relieve the pain and inflammation
of osteoarthritis and improve your dog’s mobility.
•
Response varies from dog to dog, but the
results can be quite dramatic
•
In most dogs, improvement can be seen in a
matter of days
Failure to administer RIMADYL as prescribed
may cause condition to worsen.
How should I give RIMADYL
to my dog?
RIMADYL should be given according to your
veterinarian’s instructions. Your veterinarian will
tell you what dosage of RIMADYL is right for your
dog and how often it should be given. RIMADYL
Caplets should be given by mouth. Most dogs will
take RIMADYL Chewable Tablets right out of your
hand, or the tablet can be placed in the mouth.
RIMADYL may be given with or without food.
“My dog Toby was in pain for 4 months,
and we tried a variety of medications.
RIMADYL has allowed him to be pain
free for months now and get back to
his old self. Just wanted to say thank
you for making a product that basically
saved his life and gave him the quality
of life he deserves.”
— Anna Roberts
What should I discuss with my
veterinarian before giving
RIMADYL to my dog?
•
The importance of weight control and exercise
in the management of osteoarthritis
•
The types and frequency of tests
needed before and during treatments
with RIMADYL (carprofen)
•
The risks and benefits of using RIMADYL
•
Side effects from RIMADYL or other NSAIDs
that your dog has experienced
•
If your dog has suffered from liver or kidney
disease or has had a bleeding disorder
•
If your dog has had any other medical
problems or allergies
•
All medicines that you are giving your dog or
plan to give your dog, including those you can
get without a prescription
•
If your dog is pregnant, nursing or if you have
plans to breed your dog
Who should not take RIMADYL?
•
Dogs that have had an allergic reaction to
carprofen, the active ingredient in RIMADYL
•
Dogs that have had an allergic reaction to
aspirin or other NSAIDs (e.g., etodolac,
meloxicam or deracoxib) such as hives, facial
swelling or red or itchy skin
•
Cats should not take RIMADYL. Call
your veterinarian immediately if your cat
accidentally receives RIMADYL
•
People should not take RIMADYL. Keep
RIMADYL and all medicines out of reach
of children
•
RIMADYL should not be given with other
NSAIDs or steroids
What side effects could occur
from use of NSAIDs?
Non-steroidal anti-inflammatory drugs (NSAIDs)
such as RIMADYL (carprofen) provide important
benefits. However, serious but rare side effects
have been reported in dogs taking drugs in this
class. The most common NSAID-related side
effects generally involve the stomach (such as
bleeding ulcers). Side effects can occur with or
without warning and, in rare situations, result in
kidney or liver damage or death. Look for the
following side effects that can indicate your dog
may be having a problem with an NSAID or may
have another medical problem:
• Decrease or increase in appetite
• Vomiting
• Change in bowel movements or behavior
• Yellowing of gums, skin or whites of the eyes
• Change in drinking or urinating habits
It is important to stop therapy and contact
your veterinarian immediately if you
think your dog has a medical problem or
side effect from use of RIMADYL. If you have
additional questions about possible side effects,
talk to your veterinarian.
“...the long-term administration of carprofen
provides a steadily increasing improvement of
clinical signs of osteoarthritis in dogs and does
not result in an increase of the incidence of
suspected adverse reactions.”
— Autefage et al. Efficacy and safety of the long-term oral
administration of carprofen in the treatment of osteoarthritis
in dogs. Revue Med Vet. 2007.
Insist on RIMADYL
Not all pain relievers are the same. Only
RIMADYL (carprofen) is the most prescribed
non-steroidal anti-inflammatory drug (NSAID)
for dogs that comes in easy-to-use caplets or
tasty chewables. RIMADYL is an FDA-approved
prescription medication developed by Zoetis
Inc., one of the most trusted names in veterinary
pharmceuticals.
And only RIMADYL is backed by 20 years of
research and science. In addition to treating
osteoarthritis pain, RIMADYL can also reduce the
pain and inflammation caused by orthopedic and
soft-tissue surgeries such as spays and neuters,
as well as perioperative dental pain.
For more information on
RIMADYL visit rimadyl.com
Try RIMADYL and
get FREE Rewards
The RIMADYL Rewards Program is
a rewarding way to partner with your
veterinarian to ensure the health and
well-being of your dog and help you
provide the long-term care your dog
needs. With every RIMADYL (carprofen)
purchase, earn Rewards Points that translate
into DOLLARS that can be used toward
ANY expense at your veterinary clinic.
As you continue to care for your dog with
RIMADYL, you will continue to accumulate
points on your RIMADYL Rewards Card.
To see full details, program terms and
conditions, visit myrimadylrewards.com
All trademarks are the property of Zoetis Inc.,
its affiliates and/or its licensors.
©2015 Zoetis Inc. All rights reserved. RIM-00078
They protected us.
Now we can return the favor.
Military and police K-9s are often the first to go
into harm’s way, saving many human lives. After a
lifetime of service these brave dogs can have major
health issues, including osteoarthritis (OA), due to
their stressful work, injuries or age. In retirement,
these dedicated K-9s receive no compensation or
health benefits.
In partnership with The Sage Foundation for Dogs
Who Serve and National Police Dog Foundation,
Zoetis created the RIMADYL K-9 Courage Program
to provide approximately $150,000 to provide
veterinary care for up to 500 dogs annually. This will
help ensure these courageous dogs continue to live
happy, healthy lives.
If you are a proud caregiver of a retired military or
police dog, you may be able to receive a debit card
worth $300 every year to be used on any product or
service at your veterinary clinic.
To apply, see full rules of the program or if you want
to make a difference in the lives of these brave
animals, please visit:
RIMADYLK9COURAGE.COM
freely soluble in ethanol, but practically insoluble in water at 25°C.
Rimadyl Injectable is a sterile solution containing carprofen. Each mL of Rimadyl Injectable contains 50.0 mg carprofen, 30.0 mg arginine, 88.5 mg glycocholic
Rimadyl
caplets
when
dosedhyperactivity,
at 2 mg/lb once
daily oraggressiveness.
when divided and administered at 1 mg/lb twice daily. In these 2 field studies, dogs
Behavioral:
Sedation,
lethargy,
restlessness,
Hematologic:
Immune-mediated
immune-mediated
blood based
loss anemia,
epistaxis. evaluations by the veterinarian
diagnosed
with
osteoarthritishemolytic
showedanemia,
statistically
significant thrombocytopenia,
overall improvement
on lameness
Dermatologic:
Pruritus, increased
alopecia,
pyotraumatic
moistdoses.
dermatitis (hot spots), necrotizing panniculitis/vasculitis, ventral ecchymosis.
and
owner observations
whenshedding,
administered
Rimadyl
at labeled
The vast majority of patients with drug related adverse reactions have recovered when the signs are recognized, the drug is withdrawn,
The mechanism of action of carprofen, like that of other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Two unique
and veterinary
care,have
if appropriate,
is initiated.
Owners
should be
advised of the
importance
of prostaglandins
periodic follow
up for all
2 The constitutive
cyclooxygenase,
COX-1,
synthesizes
necessary
for dogs
normalduring
gastrocyclooxygenases
been described
in mammals.
administration
anyfunction.
NSAID.The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation. Inhibition of COX-1 is thought to
intestinal andofrenal
Based
upon the blood level comparison between subcutaneous and oral administration, Rimadyl effectiveness for osteoarthritis after
formulation.
Immunologic or hypersensitivity:
swelling,
hives, erythema.
dorsoscapular
subcutaneous Facial
and oral
administration
should be similar, although there may be a slight delay in the onset of relief after
In rare situations,
death has been associated with some of the adverse reactions listed above.
subcutaneous
injection.
ADVERSE
REACTIONS:
investigational
theincaplet
formulation
with
daily
administration
of 1 selective
mg/lb, no
clinically
In an
vitro study
using canine
celltwice
cultures,
carprofen
demonstrated
inhibition
of
for COX-2
versus COX-1During
may vary
from species to studies
species.3for
4 Clinical relevance
significant
adverse
reactions
were reported.
clinical
signs
were
observed
during
studies
(n=297)
which
were similar
for
of these Some
data has
not been
shown.
Carprofen
has also
beenfield
shown
to inhibit
the release
of several
prostaglandins
COX-2 versus
COX-1.
in two inflammatory
systems: rat polymorphonuclear
leukocytes
and human
indicating
inhibition
acute (PMN
carprofen
caplet- andcell
placebo-treated
dogs. Incidences
of the(PMN)
following
wererheumatoid
observed synovial
in both cells,
groups:
vomiting
(4%),ofdiarrhea
(4%),
1
system)
chronic(3%),
(synovial
cell system)
changes
in and
appetite
lethargy
(1.4%),inflammatory
behavioralreactions.
changes (1%), and constipation (0.3%). The product vehicle served as control.
Separate
placebo-controlled,
multicenter
field studies
confirmed
the effectiveness
of Rimadyl
caplets
and injectable
for
DOSAGE AND
ADMINISTRATION:masked,
Always provide
Client Information
Sheet
with prescription.
Carefully consider
the potential
benefits
and risk of Rimadyl
approximately equipotent to indomethacin in animal models.1
be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity. The specificity of a particular NSAID
CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian.
DESCRIPTION: Rimadyl (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-methyl9H-carbazole-2-acetic acid. The empirical formula is C15H12ClNO2 and the molecular weight 273.72. The chemical structure of
carprofen is shown above. Carprofen is a white, crystalline compound. It is freely soluble in ethanol, but practically insoluble in
water at 25°C.
Rimadyl Injectable is a sterile solution containing carprofen. Each mL of Rimadyl Injectable contains 50.0 mg carprofen, 30.0 mg
arginine, 88.5 mg glycocholic acid, 169.0 mg lecithin, 10.0 mg benzyl alcohol, 6.17 mg sodium hydroxide, with additional sodium
hydroxide and hydrochloric acid as needed to adjust pH, and water for injection.
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 specificity 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. Rimadyl 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.
INDICATIONS: Rimadyl 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: Rimadyl 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 Rimadyl with other anti-inflammatory
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. Rimadyl treatment was not associated with renal toxicity or gastrointestinal ulceration in well-controlled safety studies of
up to 10 times the dose in healthy dogs. As with any parenterally injected product, good hygienic procedures should be used when
administering Rimadyl Injectable.
Rimadyl 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 Rimadyl in animals less than 6 weeks of age, 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 Rimadyl 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 It is suggested to use different sites for additional
injections. If additional pain medication is warranted after administration of the total daily dose of Rimadyl, 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.
Due to the palatable nature of Rimadyl chewable tablets, 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 Rimadyl chewable tablets
above the labeled dose, please call your veterinarian for immediate assistance and notify Zoetis at 1-888-963-8471.
INFORMATION FOR DOG OWNERS: Rimadyl, 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.
Urinary: Hematuria, polyuria, polydipsia, urinary incontinence, urinary tract infection, azotemia, acute renal failure, tubular abnormalities including acute
tubular necrosis, renal tubular acidosis, glucosuria.
acid,adverse
169.0 mg lecithin,
10.0 associated
mg benzyl alcohol,
sodium
hydroxide,
with additional
hydroxide
hydrochloric
as needed
to adjust
Serious
reactions
with6.17
thismgdrug
class
can occur
without sodium
warning
and inand
rare
situationsacid
result
in death
(seepH,
and water
for injection.
Adverse
Reactions).
Owners should be advised to discontinue Rimadyl therapy and contact their veterinarian immediately if signs of
CLINICALare
PHARMACOLOGY:
intolerance
observed. Carprofen is a non-narcotic, non-steroidal anti-inflammatory agent with characteristic analgesic and antipyretic activity
Several studies have demonstrated that carprofen has modulatory effects on both humoral and cellular immune responses.5–9 Data also indicate that
There
were no
serious
adverse events
reported during
clinical
once daily administration of 2 mg/lb. The 1following
, and PGEwith
carprofen
inhibits
the production
of osteoclast-activating
factor
(OAF),field
PGE1studies
2 by its inhibitory effect in prostaglandin biosynthesis.
categories
of abnormal
observations
were
reported.
The product
vehicle
servedand
asnearly
control.
Based upon
comparisonhealth
with data
obtained from
intravenous
administration,
carprofen
is rapidly
completely absorbed (more than 90%
10
blood plasma
areReported
achieved inin1–3
hours after
administration
1, 5, and
25 mg/kg to
bioavailable)
when administered
orally.
Percentage
of Dogs
with Peak
Abnormal
Healthconcentrations
Observations
Clinical
Fieldoral
Study
(2 mg/lb ofonce
daily)
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(n=129)
mean elimination half-life was approximately
11.7 hours
in the dog. Rimadyl is more than 99%
Observation
RIMADYL
Placebo
(n=132)
bound to plasma protein and exhibits a very small volume
Inappetence
1.6 of distribution.
1.5
Comparison of a single 25 mg dose in Beagle dogs after
Vomiting
3.1subcutaneous and oral administration demonstrated3.8that 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
Diarrhea/Soft
stool
3.1
4.5
12 hour dosing interval (as reflected by area under the curve from hours zero to 12 postdose).
Behavior change
0.8
0.8
Carprofen is eliminated in the dog primarily by biotransformation in the liver followed by rapid excretion of the resulting metabolites (the ester glucuronide of
Dermatitis
0.8
0.8 in the feces (70–80%) and urine (10–20%).
carprofen and the ether glucuronides of 2 phenolic metabolites,
7-hydroxy carprofen and 8-hydroxy carprofen)
PU/PD
0.8
—
Some enterohepatic circulation of the drug is observed.
SAPINDICATIONS:
increase Rimadyl is indicated for the relief of pain
7.8and inflammation associated with osteoarthritis and8.3
for the control of postoperative pain associated
with soft tissue and orthopedic surgeries in dogs. 5.4
ALT increase
4.5
Rimadyl should not be used in2.3
dogs exhibiting previous hypersensitivity to carprofen.
AST CONTRAINDICATIONS:
increase
0.8
ingestion by humans. For use in dogs only.
BUNWARNINGS:
increase Keep out of reach of children. Not for human
3.1 use. Consult a physician in cases of accidental 1.5
Do not use in cats.
Bilirubinuria
16.3
12.1
All dogs should undergo a thorough history and physical
laboratory tests to establish
Ketonuria
14.7 examination before initiation of NSAID therapy. Appropriate
9.1
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
Clinical
pathology parameters listed represent reports of increases from pre-treatment values; medical judgment is necessary to
Experience).
determine
clinicalAs
relevance.
PRECAUTIONS:
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
which
is responsible
for theadverse
formation reactions
of prostaglandins
arachidonic
During
investigational
studies
of surgical
pain for
theenzyme
capletcyclooxygenase
formulation, no
clinically
significant
werefrom
reported.
The
11–14 When NSAIDs inhibit prostaglandins that cause inflammation they may also inhibit those prostaglandins which maintain normal homeostatic
acid.vehicle
product
served as control.
function. These anti-prostaglandin effects may result in clinically significant disease in patients with underlying or pre-existing disease more often than in
12,14
Percentage
of DogsNSAID
withtherapy
Abnormal
Reported
in Surgical
Field Studies
with
Caplets
(2 mg/lbclinical
oncesigns.
daily)
couldHealth
unmaskObservations
occult disease which
has previously
beenPain
undiagnosed
due to the
absence
of apparent
healthy patients.
Patients with underlying renal disease for example, may experience exacerbation or decompensation of their renal disease while on NSAID therapy.11–14
Observation*
(n=148)
Placebo (n=149)
The use of parenteral fluids during surgery shouldRIMADYL
be considered
to reduce the potential risk of renal complications
when using NSAIDs perioperatively.
Vomiting
10.1
13.4
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
Diarrhea/soft
stoolsigns. Events involving suspected renal, hematologic,
6.1
gastrointestinal
neurologic, dermatologic, and hepatic effects6.0
have also been reported. Patients at
greatest
risk for renal toxicity are those that are dehydrated,
and/or hepatic
Ocular
disease
2.7on concomitant diuretic therapy, or those with renal, cardiovascular,
0
dysfunction. Concurrent administration of potentially nephrotoxic
monitoring. Concomitant use of
Inappetence
1.4 drugs should be approached cautiously, with appropriate
0
Rimadyl with other anti-inflammatory drugs, such as other NSAIDs or corticosteroids, should be avoided because of the potential increase of adverse
Dermatitis/Skin
lesion
2.0
1.3
reactions, including gastrointestinal ulcerations and/or perforations. Sensitivity to drug-associated adverse reactions varies with the individual patient.
Dysrhythmia
0.7 may experience adverse reactions from another NSAID.
0
Dogs that have experienced adverse reactions from one NSAID
Rimadyl treatment was not
associated with renal toxicity or gastrointestinal ulceration1.4
in well-controlled safety studies of up to 10 times the dose
Apnea
0 in healthy dogs. As with any
parenterally injected
product, good hygienic procedures should
Oral/Periodontal
disease
1.4 be used when administering Rimadyl Injectable. 0
Rimadyl is not recommended for use in dogs with bleeding0.7
disorders (e.g., Von Willebrand’s disease), as safety has
Pyrexia
1.3not been established in dogs with
these disorders. The safe use of Rimadyl in animals less than 6 weeks of age, pregnant dogs, dogs used for breeding purposes, or in lactating bitches
Urinary
tract
disease
1.3 of Rimadyl when administered
has not
been
established. Safety has not been established1.4
for IV or IM administration. Studies to determine the activity
Wound
drainage with other protein-bound or similarly metabolized
1.4 drugs have not been conducted. Drug compatibility
0 should be monitored closely in
concomitantly
patients requiring additional therapy. Such drugs commonly used include cardiac, anticonvulsant and behavioral medications. It has been suggested that
It is suggested to use different sites for additional injections. If additional
treatment
carprofen
may reduce the
level than
of inhalant
anesthetics needed.
* A single
dogwith
may
have experienced
more
one occurrence
of an 15event.
pain
medication
is
warranted
after
administration
of
the
total
daily
dose
of
Rimadyl,
alternative
analgesia
should
be
considered.
useThese
of another
NSAID
During investigational studies for the chewable tablet formulation, gastrointestinal signs were observed
in someThe
dogs.
signs
is not vomiting
recommended.
appropriate washout times when switching from one NSAID to another or when switching from corticosteroids use to
included
and Consider
soft stools.
NSAID
There
wereuse.
no serious adverse events reported during clinical field studies for the injectable formulation. The following categories of
abnormal
observations
were reported.
The product
control.location. Severe adverse reactions may occur if large
Due to health
the palatable
nature of Rimadyl
chewable tablets,
store outvehicle
of reach served
of dogs inasa secured
quantities of tablets are ingested. If you suspect your dog has consumed Rimadyl chewable tablets above the labeled dose, please call your veterinarian for
immediatePercentage
assistance andofnotify
Zoetis
1-888-963-8471.
Dogs
withat Abnormal
Health Observations Reported in Clinical Field Studies with the Injectable
INFORMATION FOR DOG OWNERS:
Observation*
RIMADYL (n=168)
Placebo (n=163)
Rimadyl, 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
Vomiting
10.1 reactions may include decreased appetite, vomiting,
9.2diarrhea, dark or tarry stools,
of the clinical signs associated with drug intolerance. Adverse
Diarrhea/soft
stoolconsumption, increased urination, pale gums
2.4 due to anemia, yellowing of gums, skin or white of 3.7
increased water
the eye due to jaundice, lethargy,
incoordination,
seizure,
or
behavioral
changes.
Dermatitis
0.6
1.2
Serious adverse reactions associated with this drug class0.6
can occur without warning and in rare situations result
Dysrhythmia
0.6in death (see Adverse Reactions).
Owners should be advised to discontinue Rimadyl therapy0and contact their veterinarian immediately if signs of1.2
intolerance are observed.
Swelling
The vast majority of patients with drug related adverse reactions
Dehiscence
1.2 have recovered when the signs are recognized, 0the 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.
WBC increase
13.7
6.7
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
* A single
dog may of
have
experienced
more than
onegroups:
occurrence
an diarrhea
event. (4%), changes in appetite (3%), lethargy (1.4%), behavioral changes
dogs. Incidences
the following
were observed
in both
vomitingof
(4%),
(1%), and constipation
(0.3%). The product vehicle served as control.
Post-Approval
Experience:
There not
wereall
noadverse
serious adverse
events
reported
during
clinical
field studies
withreactions
once daily administration
2 mg/lb. Thepost-approval
following categories
of abnormal
Although
reactions
are
reported,
the
following
adverse
are based onof voluntary
adverse
drug
health observations
The of
product
vehicle
served asare
control.
experience
reporting.were
The reported.
categories
adverse
reactions
listed in decreasing order of frequency by body system.
Gastrointestinal: Vomiting,
diarrhea,
constipation,
inappetence,
melena,Reported
hematemesis,
gastrointestinal
ulceration,
Percentage
of Dogs
with Abnormal
Health Observations
in Clinical
Field Study (2 mg/lb
once daily)gastrointestinal
bleeding, pancreatitis.
(n=132)
Hepatic: Observation
Inappetence, vomiting, jaundice, acute hepatic Rimadyl
toxicity,(n=129)
hepatic enzyme elevation, abnormal liverPlacebo
function
test(s),
Inappetence
1.6
1.5 Retrievers.
hyperbilirubinemia, bilirubinuria, hypoalbuminemia. Approximately one-fourth of hepatic reports were in Labrador
Vomiting
3.1 disorientation.
3.8
Neurologic:
Ataxia, paresis, paralysis, seizures, vestibular signs,
Diarrhea/Softpolyuria,
stool
4.5 tubular abnormalities
Urinary: Hematuria,
polydipsia, urinary incontinence, 3.1
urinary tract infection, azotemia, acute renal failure,
change necrosis, renal tubular acidosis, glucosuria.
0.8
0.8
includingBehavior
acute tubular
Dermatitis
0.8
0.8
Behavioral:
Sedation, lethargy, hyperactivity, restlessness, aggressiveness.
PU/PDImmune-mediated hemolytic anemia, immune-mediated
0.8
—
Hematologic:
thrombocytopenia, blood loss anemia, epistaxis.
SAP increase
7.8
8.3
Dermatologic:
Pruritus, increased shedding, alopecia, pyotraumatic
moist dermatitis (hot spots), necrotizing panniculitis/vasculitis,
ALT increase In rare situations, injection site reactions including
5.4
4.5and granulomas have
ventral ecchymosis.
necrosis, abscess and seroma formation,
AST
increase
2.3
0.8
been reported with the injectable formulation.
BUN increase
3.1
1.5
Immunologic
or hypersensitivity: Facial swelling, hives, erythema.
Bilirubinuria
16.3
12.1
In rare situations,
adverse reactions listed above.
Ketonuria death has been associated with some of the14.7
9.1
To report a suspected adverse reaction call 1-888-963-8471.
Clinical pathology parameters listed represent reports of increases from pre-treatment values; medical judgment is necessary to determine clinical
relevance.
DOSAGE
AND ADMINISTRATION: Always provide Client Information Sheet with prescription. Carefully consider the potential benefits
During
of surgical pain
for thebefore
caplet deciding
formulation,tonouse
clinically
significant
adverse
reactions
weredose
reported.
Theshortest
product vehicle
and risk
ofinvestigational
Rimadyl andstudies
other treatment
options
Rimadyl.
Use the
lowest
effective
for the
duration
served as
control.
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 Percentage
dose may of
beDogs
administered
as 2Health
mg/lbObservations
of body weight
once
daily orPain
divided
administered
1 mg/lb
(2.2
mg/kg) twice
with Abnormal
Reported
in Surgical
Fieldand
Studies
with Capletsas
(2 mg/lb
once
daily)
daily. For the control of postoperative pain, administer approximately 2 hours before the procedure. Rimadyl tablets are scored and
Observation*
Rimadyl (n=148)
(n=149)
dosage should
be calculated in half-tablet increments. Tablets
can
be halved by placing the tablet on a hardPlacebo
surface
and pressing down
Vomiting
10.1
13.4
on both sides
of the score.
Diarrhea/Soft
stool Rimadyl chewable tablets are palatable
6.1 and willingly consumed by most dogs when offered
6.0 by the owner.
Therefore,
theydisease
may be fed by hand or placed on food. Care should
dose.
Ocular
2.7 be taken to ensure that the dog consumes the complete
0
Inappetence
1.4
0
Oral/Periodontal disease
1.4
0
Wound drainage
1.4
0
The recommended
dosage
Dermatitis/Skin
lesion for subcutaneous administration to dogs
2.0 is 2 mg/lb (4.4 mg/kg) of body weight daily. The1.3total daily dose may
be administered
as either 2 mg/lb of body weight once daily or divided
and administered as 1 mg/lb (2.2 mg/kg) twice
Dysrhythmia
0.7
0 daily. For control of
Apnea pain, administer approximately 2 hours before the1.4procedure.
0
post-operative
PALATABILITY:
were readily accepted
Pyrexia A controlled palatability study was conducted which
0.7 demonstrated that Rimadyl chewable tablets 1.3
Urinary on
tractfirst
disease
1.4
1.3
and consumed
offering by a majority of dogs.
EFFECTIVENESS: Confirmation of the effectiveness of Rimadyl for the relief of pain and inflammation associated with osteoarthritis, and for the
* A of
single
dog may have
experienced
more
than
onetissue
occurrence
of an event.surgeries, was demonstrated in 7 placebo-controlled, masked studies
control
postoperative
pain
associated
with
soft
and orthopedic
During the
investigational
studies forand
the analgesic
chewable tablet
formulation,
signs
were
observedininvarious
some dogs.
These
examining
anti-inflammatory
effectiveness
ofgastrointestinal
Rimadyl caplets
and
injectable
breeds
of signs
dogs.included vomiting and
soft stools.
Separate
multicenter
field studies
confirmed
the anti-inflammatory
analgesic
effectiveness
There placebo-controlled,
were no serious adversemasked,
events reported
during clinical
field studies
for the injectable
formulation. Theand
following
categories
of abnormal of
health
observations were reported. The product vehicle served as control.
In rare situations, injection site reactions including necrosis, abscess and seroma formation, and granulomas have been reported with the injectable
To report a suspected adverse reaction call 1-888-963-8471.
andcontrol
other treatment
options before
to use Rimadyl.
Useonce
the lowest
dosebreeds
for the shortest
consistent
individual
response.
the
of postoperative
paindeciding
when dosed
at 2 mg/lb
dailyeffective
in various
of dogs.duration
In these
studies,with
dogs
presented
for
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
ovariohysterectomy,
andand
aural
surgeriesaswere
administered
Rimadyl
preoperatively
and for a maximum
of 3 days (soft
2 mg/lb of body weight cruciate
once dailyrepair
or divided
administered
1 mg/lb
(2.2 mg/kg) twice
daily. For
the control of postoperative
pain, administer
tissue)
or
4
days
(orthopedic)
postoperatively.
In
general,
dogs
administered
Rimadyl
showed
statistically
significant
reduction
approximately 2 hours before the procedure. Rimadyl tablets are scored and dosage should be calculated in half-tablet increments. Tablets can be in pain
halved compared
by placing the
on a hard surface and pressing down on both sides of the score. Rimadyl chewable tablets are palatable and willingly
scores
totablet
controls.
consumed by most dogs when offered by the owner. Therefore, they may be fed by hand or placed on food. Care should be taken to ensure that the
ANIMAL
SAFETY
STUDIES:
Laboratory studies in unanesthetized dogs and clinical field studies have demonstrated that Rimadyl is well
dog consumes
the complete
dose.
tolerated
in dogs after oral administration.
The recommended dosage for subcutaneous administration to dogs is 2 mg/lb (4.4 mg/kg) of body weight daily. The total daily dose may be administered
either animal
2 mg/lb of
body weight
once
daily orwas
divided
and administered
(2.2Beagle
mg/kg) twice
control
of post-operative
Inastarget
safety
studies,
Rimadyl
administered
orallyasto1 mg/lb
healthy
dogsdaily.
at 1,For
3, and
5 mg/lb
twice dailypain,
(1, 3administer
and 5 times
approximately
2 hours
before
thedose)
procedure.
the
recommended
total
daily
for 42 consecutive days with no significant adverse reactions. Serum albumin for a single female
PALATABILITY:
controlled
palatability
study was to
conducted
that Rimadylreturned
chewableto
tablets
were readily accepted
dog
receiving 5Amg/lb
twice
daily decreased
2.1 g/dLwhich
after demonstrated
2 weeks of treatment,
the pre-treatment
value and
(2.6 consumed
g/dL) after
first offering
by a majority
dogs.
4 on
weeks
of treatment,
and of
was
2.3 g/dL at the final 6-week evaluation. Over the 6-week treatment period, black or bloody stools were
EFFECTIVENESS:
Confirmation
of the
effectiveness
of Rimadyl
fordaily
the relief
and(2inflammation
with3osteoarthritis,
for Redness
the controlof the
observed
in 1 dog
(1 incident)
treated
with 1 mg/lb
twice
andofinpain
1 dog
incidents) associated
treated with
mg/lb twiceand
daily.
of postoperative
tissue
and
orthopedic
surgeries,
wasdaily.
demonstrated in 7 placebo-controlled, masked studies examining the
colonic
mucosapain
wasassociated
observedwith
in 1soft
male
that
received
3 mg/lb
twice
anti-inflammatory and analgesic effectiveness of Rimadyl caplets and injectable in various breeds of dogs.
Two
of 8 dogs
receiving 10 masked,
mg/lb orally
twicefield
daily
(10 times
the recommended
totaland
daily
dose) for
14 days exhibited
Separate
placebo-controlled,
multicenter
studies
confirmed
the anti-inflammatory
analgesic
effectiveness
of Rimadylhypoalbuminemia.
caplets when
The
mean
dogs
receiving
this doseatwas
lower
(2.38
g/dL)
than2each
of 2 placebo
control with
groups
(2.88 andshowed
2.93 g/
dosed
at 2 albumin
mg/lb oncelevel
dailyinorthe
when
divided
and administered
1 mg/lb
twice
daily.
In these
field studies,
dogs diagnosed
osteoarthritis
statistically
significant
overall
improvement
based
on lameness
by the veterinarian
and of
owner
observations
administered
at
dL,
respectively).
Three
incidents
of black
or bloody
stoolevaluations
were observed
in 1 dog. Five
8 dogs
exhibitedwhen
reddened
areasRimadyl
of duodenal
labeled doses.
mucosa
on gross pathologic examination. Histologic exam of these areas revealed no evidence of ulceration, but did show minimal
Based upon of
thethe
blood
level comparison
and oral administration, Rimadyl effectiveness for osteoarthritis after dorsoscapular
congestion
lamina
propria in 2between
of the 5subcutaneous
dogs.
subcutaneous and oral administration should be similar, although there may be a slight delay in the onset of relief after subcutaneous injection.
Separate placebo-controlled, masked, multicenter field studies confirmed the effectiveness of Rimadyl caplets and injectable for the control of postoperative
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
pain when dosedtotal
at 2 mg/lb
variousofbreeds
of dogs.
these
studies,the
dogsdrug
presented
for ovariohysterectomy,
cruciate
aural No
recommended
daily once
dosedaily
of 2 inmg/lb)
carprofen.
InInboth
studies,
was well
tolerated clinically
by allrepair
of theand
animals.
surgeries
were administered
Rimadyl
andthe
fortreated
a maximum
of 3 days
or 4dogs
days (orthopedic)
postoperatively.
In general,
dogs
gross
or histologic
changes
were preoperatively
seen in any of
animals.
In (soft
bothtissue)
studies,
receiving the
highest doses
had average
administered
RimadylL-alanine
showed statistically
significant reduction
pain scores compared
increases
in serum
aminotransferase
(ALT) of inapproximately
20 IU. to controls.
ANIMAL SAFETY: Laboratory studies in unanesthetized dogs and clinical field studies have demonstrated that Rimadyl is well tolerated in dogs after oral
Inadministration.
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 Rimadyl
slight redness
or rash and
diagnosed
as non-specific
dermatitis.
The(1,
possibility
exists
that these mild
In target animal
safety studies,
was administered
orallywere
to healthy
Beagle dogs
at 1, 3, and 5 mg/lb
twice daily
3 and 5 times
the recommended
lesions
were
treatment
related, days
but no
relationship
wasreactions.
observed.
total daily
dose)
for 42 consecutive
withdose
no significant
adverse
Serum albumin for a single female dog receiving 5 mg/lb twice daily
decreased
to studies
2.1 g/dL after
of treatment,
returned
pre-treatment
(2.6recommended
g/dL) after 4 weeks
of doses
treatment,
was 2.3
g/dLdogs
at thewere
final
Clinical
field
were2 weeks
conducted
with 549
dogs to
ofthe
different
breedsvalue
at the
oral
forand
14 days
(297
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
included
in a study
evaluating
1 mg/lb
twice
andof252
were
included
in a separate
evaluating
2 mg/lb
1 dog (2 incidents)
treated
with 3 mg/lb
twice
daily.daily
Redness
thedogs
colonic
mucosa
was observed
in 1 malestudy
that received
3 mg/lb
twice once
daily. daily). In
both
studies the drug was clinically well tolerated and the incidence of clinical adverse reactions for Rimadyl-treated animals was no
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
higher
placebo-treated
animals
(placebo
contained
inactive
ingredients
Rimadyl).
receiving
mg/lb twice
level inthan
the dogs
receiving this dose
was lower
(2.38 g/dL)
than each
of 2 placebo
control found
groupsin
(2.88
and 2.93 For
g/dL,animals
respectively).
Three1incidents
of daily,
the
mean
post-treatment
serum ALT
values
11 IU
greaterreddened
and 9 IU
lessofthan
pre-treatment
values
for dogsexamination.
receiving Rimadyl
black
or bloody
stool were observed
in 1 dog.
Fivewere
of 8 dogs
exhibited
areas
duodenal
mucosa on gross
pathologic
Histologicand
exam of these
areas revealed
no evidence
of ulceration,
but did significant.
show minimalFor
congestion
the lamina 2propria
2 of the
5 dogs.
placebo,
respectively.
Differences
were
not statistically
animalsofreceiving
mg/lbinonce
daily,
the mean post-treatment
In separate
safety studies
and 52and
weeks,
were administered
orally
to 11.4
mg/lb/day
(5.7 times
theplacebo,
recommended
total
serum
ALT values
were lasting
4.5 IU 13
greater
0.9respectively,
IU less thandogs
pre-treatment
values
for up
dogs
receiving
Rimadyl
and
respectively.
In
daily
dosestudy,
of 2 mg/lb)
of carprofen. In both
the drug
was well
of theand/or
animals.(AST)
No gross
or histologic
changes
were seen
the
latter
3 Rimadyl-treated
dogsstudies,
developed
a 3-fold
ortolerated
greater clinically
increasebyinall(ALT)
during
the course
of therapy.
One
in any of the treated animals. In both studies, dogs receiving the highest doses had average increases in serum L-alanine aminotransferase (ALT) of
placebo-treated
dog
had
a
greater
than
2-fold
increase
in
ALT.
None
of
these
animals
showed
clinical
signs
associated
with
laboratory
approximately 20 IU.
value changes. Changes in the clinical laboratory values (hematology and clinical chemistry) were not considered clinically significant.
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
The
1 mg/lb
daily course
therapy
was repeated
as needed
at 2-week
intervalsexists
in 244that
dogs,
for as were
long treatment
as 5 years.
described
astwice
slight redness
or rashofand
were diagnosed
as non-specific
dermatitis.
The possibility
thesesome
mild lesions
related,
but no dose
was conducted
observed. in 297 dogs of different breeds undergoing orthopedic or soft tissue surgery. Dogs were
Clinical
fieldrelationship
studies were
Clinical field studies
were
549prior
dogs of
at the daily,
recommended
oral for
doses
for 14(soft
days tissue
(297 dogs
were included
in a (orthopedic
study
administered
2 mg/lb
of conducted
Rimadyl 2with
hours
to different
surgerybreeds
then once
as needed
2 days
surgery)
or 3 days
evaluatingRimadyl
1 mg/lb twice
252 dogs
wereused
included
in a separate study
2 mg/lb
once daily). In both
studies
thetype
drugand
was severity
clinically well
surgery).
was daily
well and
tolerated
when
in conjunction
with aevaluating
variety of
anesthetic-related
drugs.
The
of
tolerated and the incidence of clinical adverse reactions for Rimadyl-treated animals was no higher than placebo-treated animals (placebo contained
abnormal
health
observation
in
Rimadyland
placebo-treated
animals
were
approximately
equal
and
few
in
number
(see
Adverse
inactive ingredients found in Rimadyl). For animals receiving 1 mg/lb twice daily, the mean post-treatment serum ALT values were 11 IU greater and 9 IU
Reactions).
The most frequent
health
observation
was
vomiting and
was observed
at approximately
theFor
same
frequency
less than pre-treatment
values for abnormal
dogs receiving
Rimadyl
and placebo,
respectively.
Differences
were not statistically
significant.
animals
receivingin
Rimadylanddaily,
placebo-treated
animals. Changes
clinicopathologic
indices
ofIU
hematopoietic,
renal, hepatic,
function
2 mg/lb once
the mean post-treatment
serum ALT in
values
were 4.5 IU greater
and 0.9
less than pre-treatment
values forand
dogsclotting
receiving
Rimadyl were
andclinically
placebo, respectively.
themean
latter study,
3 Rimadyl-treated
a 3-fold
increase
in than
(ALT) pre-treatment
and/or (AST) during
the course
of
not
significant.InThe
post-treatment
serumdogs
ALTdeveloped
values were
7.3orIUgreater
and 2.5
IU less
values
for dogs
therapy. One
placebo-treated
dog had
a greater than
2-fold
increase
in ALT. NoneAST
of these
animals
showed
signs
associated
withRimadyl
laboratory
receiving
Rimadyl
and placebo,
respectively.
The
mean
post-treatment
values
were
3.1 IUclinical
less for
dogs
receiving
and 0.2 IU
value changes. Changes in the clinical laboratory values (hematology and clinical chemistry) were not considered clinically significant. The 1 mg/lb twice
greater
for dogs
receiving
placebo.
daily course
of therapy
was repeated
as needed at 2-week intervals in 244 dogs, some for as long as 5 years.
Clinical
studieswere
on the
use ofinRimadyl
on 331 dogs
undergoing
orthopedic
or administered
soft tissue surgery.
Clinical field
field studies
conducted
297 dogsInjectable
of different were
breedsconducted
undergoing orthopedic
or soft
tissue surgery.
Dogs were
2 mg/lb ofDogs
Rimadyl
2 hours prior2tomg/lb
surgery
once daily,
as needed for22hours
days (soft
tissue
surgery) and
or 3 days
surgery).as
Rimadyl
wasfor
well2 tolerated
were
administered
ofthen
Rimadyl
subcutaneously
prior
to surgery
once(orthopedic
daily thereafter,
needed,
days (soft
when used
in conjunction
a variety of surgery).
anesthetic-related
and severity
of abnormal
health observation
andanestheticplacebo-treated
tissue
surgery)
or 3 dayswith
(orthopedic
Rimadyldrugs.
wasThe
welltype
tolerated
when
used in conjunction
withina Rimadylvariety of
animals were approximately equal and few in number (see Adverse Reactions). The most frequent abnormal health observation was vomiting and was
related
drugs.
The
type
and
severity
of
abnormal
health
observations
in
Rimadyland
placebo-treated
animals
were
approximately
observed at approximately the same frequency in Rimadyl- and placebo-treated animals. Changes in clinicopathologic indices of hematopoietic, renal,
equal
and
few
in number
Reactions).
The
abnormal
observation
was
observed
hepatic,
and
clotting
function(see
wereAdverse
not clinically
significant.
Themost
meanfrequent
post-treatment
serumhealth
ALT values
were 7.3 IU
andvomiting
2.5 IU lessand
thanwas
pre-treatment
for dogs receiving
Rimadyl
and placebo,
respectively.
mean post-treatment
AST Changes
values were
IU less for dogs receiving
and 0.2 IU
atvalues
approximately
the same
frequency
in Rimadyland The
placebo-treated
animals.
in3.1
clinicopathologic
indicesRimadyl
of hematopoetic,
greater
for dogsand
receiving
placebo.
renal,
hepatic,
clotting
function were not clinically significant. The mean post-treatment serum ALT values were 8.4 IU and 7.0 IU less
Clinical
field studies on
the use
Rimadyl
InjectableRimadyl
were conducted
on 331 respectively.
dogs undergoingThe
orthopedic
or soft tissue surgery.
were
administered
than
pre-treatment
values
forofdogs
receiving
and placebo,
mean post-treatment
AST Dogs
values
were
1.5 IU and 0.7
of Rimadyl
subcutaneously
2 hours and
priorplacebo,
to surgeryrespectively.
and once daily thereafter, as needed, for 2 days (soft tissue surgery) or 3 days (orthopedic
IU2 mg/lb
greater
for dogs
receiving Rimadyl
surgery). Rimadyl was well tolerated when used in conjunction with a variety of anesthetic-related drugs. The type and severity of abnormal health
Swelling
andinwarmth
associated with
the injection
site afterequal
subcutaneous
administration
of Rimadyl
Injectable.
These findings
observations
Rimadyl-were
and placebo-treated
animals
were approximately
and few in number
(see Adverse
Reactions).
The most frequent
abnormal
healthnot
observation
vomiting and
wasterm
observed
at the
approximately
same
in Rimadyl- and placebo-treated animals. Changes in clinicowere
clinicallywas
significant.
Long
use of
injectablethehas
notfrequency
been studied.
pathologic indices of hematopoetic, renal, hepatic, and clotting function were not clinically significant. The mean post-treatment serum ALT values were
STORAGE:
Store
tablets
at controlledvalues
roomfortemperature
15°–30°C
(59°–86°F).
Store injectable
under
refrigeration
(36°–46°F).
8.4 IU and 7.0
IU less
than pre-treatment
dogs receiving
Rimadyl and
placebo, respectively.
The mean
post-treatment
AST2°–8°C
values were
1.5 IU Once
and 0.7 IU greater
formay
dogsbe
receiving
and placebo,uprespectively.
broached,
product
storedRimadyl
at temperatures
to 25°C (77°F) for 28 days.
Swelling
and warmth
were associated
withchewable
the injectiontablets
site after
subcutaneous
of Rimadyl
These
findings were
clinically
HOW
SUPPLIED:
Rimadyl
caplets and
are
scored, andadministration
contain 25 mg,
75 mg,Injectable.
or 100 mg
of carprofen
pernot
caplet
or tablet.
significant. Long term use of the injectable has not been studied.
Each caplet size is packaged in bottles containing 30, 60, or 180 caplets. Each chewable tablet size is packaged in bottles containing 7,
STORAGE:
Store
tabletsRimadyl
at controlled
room temperature
15°–30°C
(59°–86°F).
injectable
refrigeration
30,
60, or 180
tablets.
Injectable
is supplied
in 20-mL,
amber,Store
glass,
sterile,under
multi-dose
vials.2°–8°C (36°–46°F). Once broached,
product may be stored at temperatures up to 25°C (77°F) for 28 days.
REFERENCES:
HOW SUPPLIED: Rimadyl caplets and chewable tablets are scored, and contain 25 mg, 75 mg, or 100 mg of carprofen per caplet or tablet. Each caplet
1.size
Baruth
H, et al:
Anti-Inflammatory
Drugs,tablet
Vol. size
II, Newer
Anti-Inflammatory
Drugs,
KD, ed.Rimadyl
CRC Press,
is packaged
in In
bottles
containing 30, 60, and
or 180Anti-Rheumatic
caplets. Each chewable
is packaged
in bottles containing
7, 30,Rainsford
60, or 180 tablets.
Boca
Raton,
p. 33, 1986.
Injectable
is supplied
in 20-mL, amber, glass, sterile, multi-dose vials.
2. Vane JR, Botting RM: Mechanism of action of anti-inflammatory drugs. Scand J Rheumatol 25:102, pp. 9–21, 1996.
3.REFERENCES:
Grossman CJ, Wiseman J, Lucas FS, et al: Inhibition of constitutive and inducible cyclooxygenase activity in human platelets and
1. Baruth H, etcells
al: In Anti-Inflammatory
Anti-Rheumatic
Vol. II, Newer
Anti-Inflammatory
Drugs,1995.
Rainsford KD, ed. CRC Press, Boca Raton, p. 33, 1986.
mononuclear
by NSAIDs andand
COX-2
inhibitors.Drugs,
Inflammation
Research
44:253–257,
Vane JR,AP,
Botting
RM:KM,
Mechanism
of action
of anti-inflammatory
Scandof
J Rheumatol
25:102, pp. 9–21, 1996.
4.2.Ricketts
Lundy
Seibel SB:
Evaluation
of selectivedrugs.
inhibition
canine cyclooxygenase
1 and 2 by carprofen and other
3.
Grossman CJ,
Wiseman J, Lucasdrugs.
FS, et al:
Inhibition
of constitutive
inducible cyclooxygenase
activity in human platelets and mononuclear cells by
nonsteroidal
anti-inflammatory
Am
J Vet Res
59:11, pp.and
1441–1446,
November 1998.
NSAIDs
and
COX-2
inhibitors.
Inflammation
Research
44:253–257,
1995.
5. Ceuppens JL, et al: Non-steroidal anti-inflammatory agents inhibit the synthesis of IgM rheumatoid factor in vitro. Lancet 1:528, 1982.
Ricketts AP, Lundy KM, Seibel SB: Evaluation of selective inhibition of canine cyclooxygenase 1 and 2 by carprofen and other nonsteroidal anti-inflammatory
6.4.Ceuppens
JL, et al: Endogenous prostaglandin E2 enhances polyclonal immunoglobulin production by ionically inhibiting T suppressor
drugs. Am J Vet Res 59:11, pp. 1441–1446, November 1998.
cell
activity. Cell Immunol 70:41, 1982.
5. Ceuppens JL, et al: Non-steroidal anti-inflammatory agents inhibit the synthesis of IgM rheumatoid factor in vitro. Lancet 1:528, 1982.
7.6.Schleimer
al:Endogenous
The effects
of prostaglandin
synthesis
inhibition
on the immune
response.
3:205,
1981.
Ceuppens RP,
JL, etetal:
prostaglandin
E2 enhances
polyclonal
immunoglobulin
production
by ionicallyImmunopharmacology
inhibiting T suppressor cell
activity.
Cell
8. Leung
KH,70:41,
et al:1982.
Modulation of the development
of cell mediated immunity: Possible roles of the products of cyclooxygenase and
Immunol
lipoxygenase
pathways
arachidonic
acid metabolism.
Int J Immunopharmacology
4:195, 1982.
7. Schleimer RP,
et al: Theof
effects
of prostaglandin
synthesis inhibition
on the immune response. Immunopharmacology
3:205, 1981.
9.8.Veit
BC:
Immunoregulatory
activity
of
cultured-induced
suppressor
macrophages.
Cell
Immunol
72:14,
1982.
Leung KH, et al: Modulation of the development of cell mediated immunity: Possible roles of the products of cyclooxygenase and lipoxygenase pathways
10. Schmitt
M, etacid
al: Biopharmaceutical
evaluation
of carprofen
of arachidonic
metabolism. Int J Immuno
pharmacology
4:195, 1982.following single intravenous, oral, and rectal doses in dogs. Biopharm
Drug
Dispos
11(7):585, 1990.activity of cultured-induced suppressor macrophages. Cell Immunol 72:14, 1982.
9. Veit
BC: Immunoregulatory
11.
Kore
AM:
of nonsteroidal
anti-inflammatory
drugs.
Veterinary
Clinics
of North
America,
Small
Animal
Practice
20, March
10. Schmitt
M, Toxicology
et al: Biopharmaceutical
evaluation
of carprofen following
single
intravenous,
oral, and
rectal doses
in dogs.
Biopharm
Drug
Dispos 11(7):585,
1990.1990.
12.
m inary Clinics of North America, Small Animal Practice
m 20, March 1990.
11.Binn
Kore AM:HToxicology of nonsteroidal anti-inflammatory drugs. Veter
12. Binns SH: Pathogenesis and pathophysiology of ischemic injury in cases of acute renal failure. Compend for Cont Ed 16:1, January 1994.
DMProstaglandins: Physiology and clinical implications.
m Compend for Cont
m Ed 6:11, November 1984. N m
13.BBoothe DM:
N
mmdrugs, prostaglandins, and the kidney. JAVMA 188:9, May
A MA
M
14. Rubin SI: Nonsteroidal
anti-inflammatory
1986.
H Lange DN,
DNMandsager
M
m m concentration of isoflurane in dogs. JAVMA
15. Ko CH,
RE, et al: Effects of butorphanol and carprofen on the minimal alveolar
A MA 2000.
217:1025–1028,
For a copy of the Material
Safety DataDSheet (MSDS)
M
Mcall
D 1-888-963-8471. To report adverse reactions call Zoetis Inc. at 1-888-963-8471.
NADA #141-053, NADA
#141-111, NADA
#141-199 Approved
NADA
NADA
NADA
A by FDA
DA
Based on Rimadyl Caplets PI
14036500, Revised January 2013;
Distributed by:
Rimadyl Chewable Tablets PI
14029100, Revised April 2013; and
Zoetis Inc.
Rimadyl Sterile Injectable Solution
Kalamazoo, MI 49007
PI 054577ZO, Revised January 2013.