Prescription Nonsteroidal Anti-inflammatory Drugs (Toxicity)

Etodolac is an indole acetic acid–derivative NSAID labeled for use in dogs to treat pain and inflammation associated with osteoarthritis. It is rapidly absorbed orally, with peak serum concentrations seen 2 hr after dosing. It is primarily eliminated through the bile. The elimination half-life is 8–12 hr. Etodolac appears to be well tolerated by dogs when used at the labeled dosage (10–15 mg/kg/day, PO) for 1 yr. With multiple doses, clinical signs of toxicity such as GI ulcers, vomiting, diarrhea, and weight loss can be seen at 40 mg/kg. Six of 8 dogs died or became moribund because of GI ulceration at 80 mg/kg.

Meloxicam is an enolic acid–derivative NSAID approved for use in dogs and cats for controlling pain and inflammation. Meloxicam is available as a solution for injection (5 mg/mL) and as an oral suspension. In cats, it has been approved for use as a single SC injection at 0.3 mg/kg. In dogs, the recommended initial dosage is 0.2 mg/kg, followed by 0.1 mg/kg, PO. Meloxicam has a good margin of safety in dogs. Oral administration at 0.1 mg/kg for 26 weeks was well tolerated in dogs. Some dogs at 0.3 or 0.5 mg/kg, PO, for 42 days have shown clinical signs consistent with NSAID toxicity (vomiting, diarrhea, renal effects). In cats, the margin of safety appears to be narrow; extra-label dosing at 0.1–0.2 mg/kg, PO, for a few days has caused adverse effects.

Deracoxib is a coxib COX-2 inhibitor (in vitro) used to treat osteoarthritis in dogs. It is not approved for use in cats. The recommended dosage is 1–2 mg/kg/day or 3–4 mg/kg/day as needed for postoperative pain, not to exceed 7 days of therapy. Oral bioavailability in dogs is > 90%; the time to peak serum concentration is ~2 hr. In a 14-day study of dogs that received 10 mg/kg, no clinically observable adverse effects were seen. Dogs that received 25 mg/kg/day, 50 mg/kg/day, or 100 mg/kg/day for 10–11 days showed vomiting and melena; no hepatic or renal lesions were seen in these dogs. Dogs ingesting >100 mg/kg should be aggressively decontaminated and treated with IV fluids to prevent renal damage.

Piroxicam is an oxicam derivative. It is not approved in dogs and cats but has been used at 0.3 mg/kg, PO, every other day. Piroxicam in dogs and people has a long half-life (40 hr and 50 hr, respectively) likely due to extensive enterohepatic recirculation. The LD₅₀ of piroxicam in dogs is >700 mg/kg. Adverse GI effects were seen in 18% of dogs given piroxicam at 0.3 mg/kg/day, PO, for several months.

Diclofenac is a phenylacetic acid derivative structurally related to meclofenamate sodium and mefenamic acid. After a single injection of diclofenac sodium at 1 mg/kg in dogs, 35%–40% is excreted in the urine. The reported oral LD₅₀ of diclofenac sodium in dogs is 500 mg/kg.

Indomethacin is an indole acetic acid derivative available as the base and as the sodium trihydrate salt. The drug is structurally and pharmacologically related to another NSAID, sulindac. The reported oral LD₅₀ of indomethacin in rats is 12 mg/kg. Administration of indomethacin to dogs at 2 mg/kg for 30 days resulted in GI ulcers in 60% of dogs and perforation in 20%.

Etodolac, an indole acetic acid derivative, is used for pain relief, osteoarthritis, and rheumatoid arthritis in people. It is approved in the USA for use in dogs (>12 mo old) to manage pain and inflammation associated with osteoarthritis. The suggested dosage in dogs is 10–15 mg/kg. Etodolac is well absorbed orally in dogs, with peak plasma concentration seen in 2 hr. It is primarily excreted through bile, and the half-life in dogs is 8–12 hr. In dogs, etodolac at 40 mg/kg/day was associated with GI ulcers, weight loss, emesis, and local occult blood loss. Dosages of 80 mg/kg/day caused 6 of 8 dogs to die or become moribund because of GI ulceration.

Nabumetone differs from other NSAIDs in that it is neutral as opposed to acidic. The risk of GI ulcers from nabumetone is considered less than that of other NSAIDs. Nabumetone is primarily excreted in the urine in most species. However, in dogs, when nabumetone was administered at 20 mg/kg, only 27% of the dose was found in the urine. The reported oral LD₅₀ of nabumetone in rats is >2 g/kg. At a dosage of >300 mg/kg, the lower GI tract and the kidneys were affected in rats, mice, rabbits, and rhesus monkeys.