RIMADYL LABEL INFO
RIMADYL LABEL INFO
RIMADYL LABEL(carprofen)
Caplets/Chewable Tablets
Non-steroidal anti-inflammatory drug
For oral use in dogs only
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.
The chemical name for
Rimadyl, a substituted carbazole, is (±)-6-chloro-a-methylcarbazole-2-acetic
acid and its structural
formula is:
Carprofen is a white, crystalline compound with an empirical formula of
C15H12NO2Cl and a
molecular weight of 273.72. It is freely soluble in ethanol, but practically
insoluble in water at 25°C.
CLINICAL PHARMACOLOGY: Carprofen is a non-narcotic, non-steroidal
anti-inflammatory
agent with characteristic analgesic and antipyretic activity approximately
equipotent to indomethocin
in animal models.1
As with other NSAIDs, the exact mode of action of carprofen has not been
established; however,
inhibition of prostaglandin synthesis accounts for at least part of its
mode of action. Carprofen is a
reversible inhibitor of cyclo-oxygenase and a moderately potent inhibitor
of phospholipase A2.
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
In rats, carprofen has been shown to be a much weaker blocker of arachidonic
acid-induced diarrhea
than indomethocin.2 This decreased effect of carprofen on prostaglandin
synthesis in the
gastrointestinal tract may explain its relatively low ulcerogenic activity
compared to other drugs in its
class.1
Several studies have demonstrated that carprofen has modulatory effects
on both humoral and cellular
immune responses.3-7 Data also indicate that carprofen inhibits the production
of osteoclast-activating
factor (OAF), PGE1, and PGE2 by its inhibitory effects on 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.8 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.
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 in dogs.
DOSAGE AND ADMINISTRATION: The recommended dosage for oral administration
to dogs is
1 mg/lb of body weight twice daily. Rimadyl caplets and 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. Rimadyl chewable
tablets are palatable and
willingly 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 dog consumes the
complete dose.
PALATABILITY: A controlled palatability study was conducted which
demonstrated that Rimadyl
chewable tablets were readily accepted and consumed on first offering by
a majority of dogs.
SAFETY: Laboratory studies and clinical field trials have demonstrated
that Rimadyl is well tolerated
in dogs after oral administration. In target animal safety studies, Rimadyl
was administered to dogs at
1, 3, and 5 times the recommended dose for 42 consecutive days with no
significant adverse
reactions. Serum albumin for a single female dog receiving 5 times the
recommended dose 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
the recommended dose and
in 1 dog (2 incidents) treated with 3 times the recommended dose. Redness
of the colonic mucosa
was observed in 1 male that received 3 times the recommended dose.
Two of 8 dogs receiving 10 times the recommended dose (10 mg/lb twice daily)
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 stools were observed in 1 dog. Five of 8 dogs exhibited
reddened areas of duodenal
mucosa on gross pathologic examination. Histologic examination 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
up to 11.4 mg/lb/day
(5.7 times the recommended total daily dose) 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 297 dogs of different breeds
at the recommended dose for
14 days. The drug was clinically well tolerated and the incidence of clinical
adverse reactions for
Rimadyl-treated animals was no higher than placebo-treated animals (placebo
contained inactive
ingredients found in Rimadyl). Mean post-treatment serum ALT values were
11 IU greater and 9 IU
less than pre-treatment values for dogs receiving Rimadyl and placebo,
respectively. Differences were
not statistically significant. Changes in clinical laboratory values (hematology
and clinical chemistry)
were not considered clinically significant nor reported as adverse reactions.
The recommended
course of therapy was repeated as needed at 2-week intervals in 244 of
the dogs, some for as long
as 5 years.
CONTRAINDICATIONS: Rimadyl should not be used in dogs exhibiting
previous hypersensitivity
to carprofen.
PRECAUTIONS: As a class, cyclo-oxygenase inhibitory NSAIDs may be
associated with
gastrointestinal and renal toxicity. Effects may result from decreased
prostaglandin production and
inhibition of the enzyme cyclo-oxygenase which is responsible for the formation
of prostaglandins
from arachidonic acid.9-12 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.10,12 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.9-12
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. Since many NSAIDs
possess the potential to
induce gastrointestinal ulceration, concomitant use of Rimadyl 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, Rimadyl treatment
was not associated with renal toxicity or gastrointestinal ulceration in
well-controlled safety studies of
up to ten times the dose in dogs.
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
pregnant dogs, dogs used for breeding purposes, or in lactating bitches
has not been established.
Studies to determine the activity of Rimadyl when administered concomitantly
with other
protein-bound drugs have not been conducted. Drug compatibility should
be monitored closely in
patients requiring additional therapy.
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 Pfizer Animal Health (1-800-366-5288).
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. 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 Rimadyl 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.
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 and
Adverse Reactions).
ADVERSE REACTIONS: During investigational studies for the caplet
formulation, 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.
During investigational studies for the chewable tablet formulation, gastrointestinal
signs were observed
in some dogs. These signs included vomiting and soft stools.
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, inappetence, melena, hematemesis,
gastrointestinal
ulceration, gastrointestinal bleeding, pancreatitis.
Hepatic (liver): Inappetence, vomiting, jaundice, acute hepatic
toxicity, hepatic enzyme elevation,
abnormal liver function test(s), hyperbilirubinemia, hyperbilirubinuria,
hypoalbuminemia.
Approximately one-fourth of hepatic reports were in Labrador Retrievers.
Neurologic (nerve): 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 (blood): Immune-mediated hemolytic anemia, immune-mediated
thrombocytopenia, blood loss
anemia, epistaxis.
Dermatologic (skin): 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 a suspected adverse reaction call 1-800-366-5288.
STORAGE: Store at controlled room temperature 15°–30°C (59°–86°F).
HOW SUPPLIED: Rimadyl 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
60 or 180 tablets. Rimadyl
caplets are scored and contain 25 mg, 75 mg, or 100 mg of carprofen per
caplet. Each caplet size is
packaged in bottles containing 100 or 250 caplets.
REFERENCES:
1. Baruth H, et al.: In Anti-Inflammatory and Anti-Rheumatic Drugs, Vol.
II, Newer
Anti-Inflammatory Drugs, Rainsford KD, ed. CRC Press, Boca Raton, p. 33,
1986.
2. Strub KM, et al.: Relation between ulcerogenic activity of various NSAIDs
and their potency as
inhibitors of prostaglandin synthesis in vivo. In Arachidonic Acid Metabolism
in Inflammation and
Thrombosis. Brune K, Baggiolini M, eds. Birkhauser Verlag, Basel, p. 245,
1979.
3. Ceuppens JL, et al.: Non-steroidal anti-inflammatory agents inhibit
the synthesis of IgM rheumatoid
factor in vitro. Lancet 1:528, 1982.
4. Ceuppens JL, et al.: Endogenous prostaglandin E2 enhances polyclonal
immunoglobulin production
by ionically inhibiting T suppressor cell activity. Cell Immunol 70:41,
1982.
5. Schleimer RP, et al.: The effects of prostaglandin synthesis inhibition
on the immune response.
Immunopharmacology 3:205, 1981.
6. Leung KH, et al.: Modulation of the development of cell mediated immunity:
Possible roles of the
products of cyclo-oxygenase and lipoxygenase pathways of arachidonic acid
metabolism. Int J
Immunopharmacology 4:195, 1982.
7. Veit BC: Immunoregulatory activity of cultured-induced suppressor macrophages.
Cell Immunol
72:14, 1982.
8. Schmitt M, et al.: Biopharmaceutical evaluation of carprofen following
single intravenous, oral, and
rectal doses in dogs. Biopharm Drug Dispos 11(7): 585, 1990.
9. Kore AM: Toxicology of nonsteriodal anti-inflammatory drugs. Veterinary
Clinics of North
America, Small Animal Practice 20, March 1990.
10. Binns SH: Pathogenesis and pathophysiology of isochemic injury in cases
of acute renal failure.
Compend for Cont Ed 16:1, January 1994.
11. Boothe DM: Prostaglandins: Physiology and clinical implications. Compend
for Cont Ed 6:11,
November 1984.
12. Rubin SI: Nonsteriodal anti-inflammatory drugs, prostaglandins, and
the kidney, JAVMA 188:9,
May 1986.
For a copy of the Material Safety Data Sheet (MSDS) or to report adverse
reactions call Pfizer
Animal Health at 1-800-366-5288. NADA #141-111, Approved by FDA NADA #141-053,
Approved by FDA
 |
 |
Peanut Butter Bark Bar Kitties (2.5") for your Dog! profits go to Great Dane Rescue, Inc |
|
|
||||||||||||||||||||||
READmy Guest Book |
Timber Creek Acres Crates |
||||||||||||||||||||||
