(for veterinary information only)
BRAND NAME: ETOGESIC, LODINE
EEtodolac is a member of the class of drugs known as NSAIDs (non-steroidal anti-inflammatory drugs), the same class as such common over-the-counter remedies as Advil (Ibuprofen), Aleve (Naproxen), and aspirin. This class of drug is used for pain relief successfully in humans but the development of safe NSAIDs for pets has only been achieved relatively recently.
The problem with the pet use of NSAID's made for humans has been unacceptable (even life-threatening) side effects:
The veterinary profession had been in need of an NSAID that could effectively relieve pain without the above risks. In 1997, Pfizer Animal Health released the first NSAID for dogs in the U.S. as the answer to this need. This product was carprofen which had been available in the U.K. since 1994 and has earned a reputation for effectiveness and safety. In 1998, etodolac was the second veterinary NSAID to be released for the veterinary market, though it had been previously available in the human market for some time.
This new plane of safety was made possible by new biochemical knowledge. Inflammatory biochemicals responsible for the pain and inflammation we want to alleviate are produced by an enzyme called “cyclo-oxygenase 2” or simply "COX-2." The goal is to inhibit this enzyme without inhibiting its counterpart “cyclo-oxygenase 1.” Cyclo-oxygenase 1, abbreviated COX-1, is what is called a “constitutive” enzyme. This means it is involved in producing regulatory biochemicals (called “prostaglandins”) which are important in maintaining the normal health and function of our bodies. We want to leave this enzyme alone. Cyclo-oxygenase 2, abbreviated COX-2, produces inflammation but also is important in regulating kidney blood flow and in some reproductive and central nervous system function. We want to inhibit COX-2 in such a way that we do not disrupt its healthful functions.
In the past, NSAIDs could not distinguish the COX enzymes and inhibited them both. With the development of “COX preferential” and “COX selective” NSAIDs, we can inhibit COX-2 and leave COX-1 alone. The introduction of COX-2 preferential NSAIDs has reduced stomach and intestinal side effects by 50% in humans and has made FDA approval of certain NSAIDs possible for pets.
HOW THIS MEDICATION IS USED
Etodolac is used in the treatment of pain either for short term or long term use. It has been licensed for once a day use (i.e. the dose for the entire day can be given all at once).
A dog that is potentially a candidate for long term use of any NSAID should have a complete examination by the veterinarian, a screening blood panel to establish baseline biochemical values, and ideally some kind of recheck testing two weeks after starting the NSAID. This is because most adverse reactions, unusual as they may be, occur within this initial time frame and it is important that they be recognized before they get out of hand. After this initial period, complete blood panels should be screened every six months, an important step with any medication for long term use, not just the NSAIDs.
Etodolac is approved only for canine use officially and was designed for long term use in dogs. Do not use this medication in any cat. At this time, use of NSAIDs in the cat is limited to meloxicam and robenacoxib.
The side effects of concern are the same with all NSAIDs: stomach ulceration, loss of kidney function, and inappropriate bleeding, though etodolac has a special side effect of concern: “Dry Eye” (keratoconjunctivitis sicca). Development of these side effects are dependent both on the dose of medication used and on risk factors of the host (for example: an aged pet may not efficiently clear a dose of medication from its body leading to stronger and longer activity of the drug). There is also a particular idiosyncratic reaction for NSAIDs which has received a great deal of press. An idiosyncratic reaction is one that is not dose-dependent nor predictable by any apparent host factor; it simply happens out of the blue. This particular idiosyncratic reaction is a liver toxicity which is so rare that it did not show up in any of the initial 400 test subjects, nor in the U.K. use of the carprofen and was not recognized until carprofen was used in over a million dogs in the U.S. after its release as the first NSAID. While it was carprofen use which allowed this reaction to be discovered, it is now generally agreed that any veterinary NSAID could yield this reaction (simply using an NAID other than carprofen will not prevent this potential reaction). We will review this reaction as well as the other side effects below.
The hepatopathy reaction usually occurs in the first 3 weeks
It is important to realize that COX-selectivity is not the sole factor in safety. In humans, the incidence of kidney function-related side effects was unchanged by the development of COX-2 preferential NSAIDs and we expect the same is true with dogs. Still, these drugs have an excellent track record for safety. The important issue is to recognize risk factors for adverse reactions and take preventive steps (see the Concerns and Cautions section below). Many exaggerated reports and rumors have surfaced on the internet and it is important to consider only confirmed and properly investigated information.
INTERACTIONS WITH OTHER DRUGS
Drugs of the NSAID class should not be used concurrently as the potential for the aforementioned side effects increases. For similar reasons, NSAIDS should not be used in conjunction with corticosteroid hormones such as prednisone, dexamethasone etc. Zoetis (formerly Pfizer Animal Health) recommends a 5-7 day rest period when changing over to carprofen or to another NSAID from carprofen and this rule seems judicious for changing to NSAIDs other than carprofen. Aspirin poses an exception due to its strong platelet inactivating abilities so 10-14 days is recommended when switching to a veterinary NSAID from aspirin. Allow at least one week between prednisone and a veterinary NSAID.
If etodolac is used concurrently with phenobarbital, it is especially important that appropriate liver monitoring be performed. (Our hospital recommends bile acids testing every 6 months for dogs on phenobarbital.) These two drugs interact such that neither may work well if they are used together.
ACE inhibitors such as enalapril or benazepril may not be as effective in the presence of etodolac. (ACE inhibitors are used in the treatment of hypertension or heart failure.) This is because ACE inhibitors depend on the dilation of blood vessels in the kidneys and such dilation can be interfered with by NSAIDs). The diuretic effect of furosemide may be reduced with concurrent etodolac and digoxin (a heart medicine) may achieve higher than normal blood levels. All of these side effects are particularly relevant to heart failure patients.
When combined with cyclosporine, an immunomodulator, etodolac may produced increased blood levels of cyclosporine and thus increase the potential for cyclosporine side effects.
CONCERNS AND CAUTIONS
Etodolac has not been tested in pregnant or nursing females and thus is not recommended for use in such individuals, particularly since COX-2 is important in reproductive function. This also means that pregnant women might do well not handling this medication.
Etodolac should not be used in dogs with pre-existing liver or kidney disease. In order to screen for pre-existing liver or kidney disease it is a good idea to run a blood chemistry panel prior to starting long term etodolac.
It is probably prudent to periodically monitor tear function in patients on etodolac.
ANY DOG ON LONG TERM MEDICATION OF ANY KIND
Etodolac should not be used in patients with pre-existing GI ulcerations.
Safety has not been established for etodolac in patients under 12 months of age.
Etodolac, like the other veterinary NSAIDs, may alter thyroid test results.
To read the product insert for Etogesic, click here:
Page last updated: 9/24/2016