ETODOLAC

Chemistry/Storage, Stability, Compatibility

An indole acetic acid derivative non-steroidalantiinflammatory agent (NSAID), etodolac occurs as a white, crystalline compound that is insolublein water, but soluble in alcohol or DMSO.
The commercially available veterinary tablets should be stored at controlled room temperature (15-30°C).

Pharmacology - ETODOLAC

Like other NSAIDs, etodolac has analgesic, antiinflammatory and antipyrexicactivity. Etodolac appears to be more selective for inhibition of cyclooxygenase-2 than cyclooxygenase-1. This means that the drug should possess greater inhibition of the prostaglandins involved with pain and inflammation than those involved with cytoprotection of the GI tract and renal tissue. Etodolac is also thought to inhibit macrophage chemotaxis, which may explain some of its antiinflammatory activity.

Uses, Indications

Etodolac is labeled for the management of pain and inflammation associatedwith osteoarthritis in dogs. It may find uses however for a variety of conditions where pain and/orinflammation should be treated.

Pharmacokinetics - ETODOLAC

After oral administration to healthy dogs, etodolac is rapidly and nearlycompletely absorbed. The presence of food may alter the rate, but not the extent of absorption. Peakserum levels occur about 2 hours post dosing. Etodolac is highly bound to serum proteins. Thedrug is primarily excreted via the bile into the feces. Glucuronide conjugates have been detected inthe bile but not the urine. Elimination half life in dogs varies depending whether food is present inthe gut, which may affect the rate of enterohepatic circulation of the drug. These values range fromabout 8 hours (fasted) to 12 hours (non-fasted).

Contraindications, Precautions, Reproductive Safety

Etodolac is contraindicated in dogspreviously found to be hypersensitive to it. It should be used with caution in dogs with preexistingor occult GI, hepatic, cardiovascular or hematologic abnormalities as NSAIDs may exacerbate theseconditions. Patients may be more susceptible to renal injury from etodolac if they are dehydrated, on diuretics, or have preexisting renal, hepatic or cardiovascular dysfunction.
Safety of etodolac hs not been established in dogs less than 12 months of age. Safe use has alsonot been established in breeding, pregnant, or lactating dogs. Use only when the benefits clearlyoutweigh the potential risks of use in these animals.

Adverse Effects, Warnings

In clinical field studies, etodolac's primary adverse effect wasvomiting/regurgitation, reported in about 5% of dogs tested. Diarrhea, lethargy, and hypoproteinemia were also reported in a small number of dogs. Urticaria, behavioral changes and inappetence were reported in less than 1% of dogs treated. It must be remembered however, that as thedrug is used in many more dogs for significant periods of time, additional adverse effects maysurface.
The manufacturer warns to terminate therapy if inappetence, vomiting, fecal abnormalities oranemia are observed.
Overdosage - Limited information is available, but in a safety study where dogs were given 40mg/kg/day (2.7X) GI ulcers, weight loss, emesis and local occult blood were noted. Doses of 80mg/kg/day (5.3X), caused 6 of 8 dogs to either die or become moribund secondary to GI ulceration.
It should be noted that these were not single dose overdoses. However, they do demonstrate thatthere is relatively narrow therapeutic window for the drug in dogs and that doses should becarefully determined (i.e., do not confuse mg/kg dosages with mg/lb).

Drug Interactions

Note: Although the manufacturer does not list any specific drug interactionsin the package insert, it does caution to avoid or closely monitor etodolac's use with other drugs, especially those that are also highly protein bound. It also recommends closely monitoring, oravoiding using etodolac with any other ulcerogenic drugs (e.g., corticosteroids, other NSAIDs).
In humans, there are many interactions possible with NSAIDs. Because clinical experience islimited in dogs, the following may or may not be clinically significant. Because etodolac is highlybound to plasma proteins, it may displace other highly bound drugs. Increased serum levels andduration of actions of phenytoin, valproic acid, oral anticoagulants, other anti-inflammatoryagents, salicylates, sulfonamides, and the sulfonylurea antidiabetic agents may occur.
When aspirin is used concurrently with etodolac, plasma levels of etodolac could decrease and anincreased likelihood of GI adverse effects (blood loss) could occur. Concomitant administration ofaspirin with etodolac cannot be recommended.
Probenecid may cause a significant increase in serum levels and half-life of etodolac.
Serious toxicity has occurred when NSAIDs have been used concomitantly with methotrexate;use together with extreme caution.
Etodolac may reduce the saluretic and diuretic effects of furosemide and increase serum levels ofdigoxin. Use with caution in patients with severe cardiac failure.