ETODOLAC

By | 2010-05-08

Chemistry – Storage – Stability – Compatibility

An indole acetic acid derivative non-steroidal antiinflammatory agent (NSAID), etodolac occurs as a white, crystalline compound that is insoluble in water, but soluble in alcohol or DMSO.

The commercially available veterinary tablets should be stored at controlled room temperature (15-30°C).

Pharmacology

Like other NSAIDs, etodolac has analgesic, antiinflammatory and antipyrexic activity. 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 associated with osteoarthritis in dogs. It may find uses however for a variety of conditions where pain and/or inflammation should be treated.

Pharmacokinetics

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

Contraindications – Precautions – Reproductive Safety

Etodolac is contraindicated in dogs previously found to be hypersensitive to it. It should be used with caution in dogs with preexisting or occult GI, hepatic, cardiovascular or hematologic abnormalities as NSAIDs may exacerbate these conditions. 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 also not been established in breeding, pregnant, or lactating dogs. Use only when the benefits clearly outweigh the potential risks of use in these animals.

Adverse Effects – Warnings

In clinical field studies, etodolac’s primary adverse effect was vomiting/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 the drug is used in many more dogs for significant periods of time, additional adverse effects may surface.

The manufacturer warns to terminate therapy if inappetence, vomiting, fecal abnormalities or anemia are observed.

Overdosage

Limited information is available, but in a safety study where dogs were given 40 mg/kg/day (2.7X) GI ulcers, weight loss, emesis and local occult blood were noted. Doses of 80 mg/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 that there is relatively narrow therapeutic window for the drug in dogs and that doses should be carefully determined (i.e., do not confuse mg/kg dosages with mg/lb).

Drug Interactions

Note: Although the manufacturer does not list any specific drug interactions in 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, or avoiding using etodolac with any other ulcerogenic drugs (e.g., corticosteroids, other NSAIDs).

In humans, there are many interactions possible with NSAIDs. Because clinical experience is limited in dogs, the following may or may not be clinically significant. Because etodolac is highly bound to plasma proteins, it may displace other highly bound drugs. Increased serum levels and duration of actions of phenytoin, valproic acid, oral anticoagulants, other anti-inflammatory agents, salicylates, sulfonamides, and the sulfonylurea antidiabetic agents may occur.

When aspirin is used concurrently with etodolac, plasma levels of etodolac could decrease and an increased likelihood of GI adverse effects (blood loss) could occur. Concomitant administration of aspirin 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 of digoxin. Use with caution in patients with severe cardiac failure.

Doses

Doses for dogs:

a) For treatment of pain and inflammation associated with osteoarthritis: 10-15 mg/kg PO once daily. Dogs less than 5 kg cannot be accurately dosed with EtoGesic®. Adjust dose to obtain satisfactory response, but do not exceed 15 mg/kg. For long term therapy, reduce dose level to minimum effective dosage. (Package Insert; EtoGesic® — Fort Dodge)

Monitoring Parameters

Efficacy and adverse effects

Client Information

Because etodolac is a new drug for use in dogs, clients should be cautioned to monitor and report any significant change in the animal’s health to the veterinarian.

Dosage Forms/Preparations/FDA Approval Status

Veterinary-Approved Products:

Etodolac 150 mg and 300 mg scored tablets in bottles of 100 & 250; EtoGesic® (Fort Dodge); (Rx) Approved for use in dogs.

Human-Approved Products:

Etodolac 200 mg, 300 mg oral capsules and 400 mg, 500mg tablets; Lodine® (Wyeth-Ayerst); Rx