Small Animal/Exotics
PHARM PROFILE
ETODOLAC
GiGi Davidson, BS, RPh
North Carolina State University
E
todolac is a pyranocarboxylic
acid nonsteroidal antiinflam-
matory drug (NSAID) that is
used to manage pain and inflamma-
tion in dogs with osteoarthritis.
PHARMACOLOGY
Etodolac acts primarily through
inhibition of the enzyme cyclooxyge-
nase (COX)-2, which catalyzes for-
mation of proinflammatory prosta-
glandins. 1,2 Agents that selectively
block COX-2 are preferred to those
that block both COX-1 and COX-2
(e.g., aspirin, flunixin, phenylbuta-
zone, piroxicam) because COX-1 in-
hibition leads to gastrointestinal ero-
sion and renal lesions. Etodolac also
reportedly inhibits macrophage che-
motaxis in vitro and in vivo, further
contributing to its antiinflammatory
activity.3 Etodolac has been shown to
improve the ground reaction forces
(i.e., the amount of force a dog will
place on a limb, indicating whether
the limb is being favored because of
pain) in dogs with osteoarthritis of
the hip joint, indicating significant
pain reduction in these patients.4
Etodolac is well absorbed after oral
dosing5; maximum blood concentra-
tions and onset of action occur 30 to
60 minutes after administration. 6
Pharm Profile introduces drugs that are new to the veterinary market as well as new indications for existing drugs. If you would like
Pharm Profile to cover a particular agent, please contact column editor GiGi Davidson, BS, RPh, North Carolina State University,
4700 Hillsborough Street, Raleigh, NC 27606; phone 919-821-9500 • fax 919-829-4225 • email gigi_davidson@ncsu.edu.
20TH ANNIVERSARY
Etodolac undergoes extensive entero-
hepatic recirculation in dogs, result-
ing in a serum half-life of 9.7 to 14.4
hours,4 thus allowing for once-daily
dosing.
INDICATIONS
Etodolac is approved for the man-
agement of pain and inflammation as-
sociated with osteoarthritis in dogs.7
CAUTIONS
All COX inhibitors have the po-
tential to induce gastric ulceration
and renal toxicity; even COX-2 selec-
tive NSAIDs inhibit COX-1 to some
degree. Etodolac should be used with
caution in patients that are dehydrat-
ed; are receiving concomitant diuretic
therapy; or have renal, cardiovascular,
and/or hepatic dysfunction.9 Etodo-
lac has not been studied in cats, and be-
cause of the toxicity of other NSAIDs
in this species, its use in cats is not
recommended.
Side Effects
Etodolac has been reported to in-
duce vomiting, diarrhea, and hypo-
proteinemia in some dogs receiving
therapeutic doses.4 Gastric ulceration
has also been reported in dogs receiv-
ing etodolac at doses higher than 15
mg/kg.7
Use in Pregnancy
The use of etodolac in pregnancy
is not recommended; its use in breed-
Compendium June 1999
ing, pregnant, or lactating dogs and
in dogs younger than 12 months of
age has not been investigated.7
ACUTE TOXICITY
Acute overdose in dogs has not
been reported. In preclinical trials,
doses of 25 to 80 mg/kg admin-
istered chronically (3 to 12 months)
resulted in vomiting, diarrhea, weight
loss, anemia from gastric and intesti-
nal ulceration, and death.7 Symptoms
of acute overdose in humans include
nausea, vomiting, lethargy, epigastric
pain, hypertension, acute renal fail-
ure, and respiratory depression.10 Be-
cause there are no antidotes, support-
ive measures that should be employed
in the event of an overdose include
induction of emesis or gastric lavage,
administration of charcoal to de-
crease further absorption, and admin-
istration of a cytoprotective drug (e.g.,
sucralfate, 500 mg to 1 g two to three
times daily).
DRUG INTERACTIONS
Because all NSAIDs may poten-
tially induce gastric and renal toxici-
ty, concurrent use of etodolac with
other NSAIDs (e.g., aspirin, phenyl-
butazone, carprofen, ibuprofen, keto-
profen) is not recommended. Eto-
dolac increases serum levels of
cyclosporine, lithium, methotrexate,
and digoxin (related to decreased re-
nal excretion), thereby escalating the
risk of toxicity of these drugs.11
Compendium June 1999 20TH ANNIVERSARY
Client Counseling Information
■ Etodolac is used to relieve pain and inflammation
in dogs.
■ Etodolac is a very safe drug; however, some dogs
may have adverse reactions. If your dog shows
signs of vomiting, diarrhea, or inappetence or if
you notice blood in its stool, you should
immediately stop giving the drug and contact your
veterinarian.
■ Tell your veterinarian if your dog is taking any
medications other than etodolac. You should not
give your dog any other pain medications, such as
aspirin, while it is taking etodolac.
DOSAGE AND ADMINISTRATION
The recommended dose in dogs is 10 to 15 mg/kg orally
once daily. Once a satisfactory clinical response is achieved,
the dose should be adjusted to the lowest effective dose for
lifetime management of osteoarthritis.
PREPARATIONS
EtoGesic® (Fort Dodge, Ft. Dodge, IA) is available in
150- and 300-mg scored tablets and comes in bottles of
100 and 250 tablets. The average wholesale price per tablet
is $0.30 for 300-mg tablets and $0.24 for 150-mg tablets.
The aqueous stability of this drug in suspension has not
been investigated; therefore compounding this drug into a
suspension is not recommended.
Small Animal/Exotics
STORAGE AND HANDLING
Etodolac tablets should be stored at a controlled room
temperature (15˚C to 30˚C [59˚F to 86˚F]).
REFERENCES
1. Humber LG: Etodolac: The chemistry, pharmacology, metabolic dis-
position and clinical profile of a novel anti-inflammatory pyrano-
carboxylic acid. Med Res Rev 7:1, 1987.
2. Humber LG: On the classification of NSAIDs. Drug News Perspect
5:102–103, 1992.
3. Gervais G, Martel RR, Skamene E: The effect of the nonsteroidal
anti-inflammatory drug etodolac on macrophage migration in vitro
and in vivo. J Imunopharmacol 6:205–214, 1984.
4. Budsberg SC, Johnston SA, Schwarz PD, et al: Efficacy of etodolac
for the treatment of osteoarthritis of the hip joints in dogs. JAVMA
214(2):206–210, 1999.
5. Kraml M, Cosyns L, Hicks DR, et al: Bioavailability studies with
etodolac in dogs and man. Biopharm Drug Dispos 5:63–74, 1984.
6. Cayen MN, Kraml M, Ferdinandi ES, et al: The metabolic disposi-
tion of etodolac in rats, dogs and man. Drug Metabol Rev 12:363–
377, 1981.
7. Freedom of Information Summary: NADA141–108 (original), Eto-
Gesic® for Dogs (etodolac), 1998.
8. Vane JR: Inhibition of prostaglandin synthesis as a mechanism of ac-
tion for aspirin-like drugs. Nat New Biol 231:232–235, 1971.
9. Fry SW, Seeff LB: Hepatotoxicity of analgesics and anti-inflammato-
ry agents. Gastroenterol Clin North Am 24:875–905, 1995.
10. Boldy DA, Hale KA, Val JA: Etodolac overdose. Human Toxicol
7(2):203–204, 1988.
11. Kastrup C (ed): Drug Facts and Comparisons. St Louis, MO, Facts and
Comparisons, 1998, p 251e.
About the Author
Ms. Davidson is the Director of Pharmacy, College of
Veterinary Medicine, North Carolina State Universi-
ty, Raleigh, North Carolina.