Abstract

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam family. It has potent anti-inflammatory, analgesic and antipyretic properties. It acts by inhibition of the enzyme cyclooxygenase (COX) which in turn inhibits the biosynthesis of prostaglandins and other autocoids. These substances are effective biologic mediators that are involved in many physiologic functions as well as pathologic conditions.¹ Meloxicam has 3-fold greater activity against the inducible inflammatory response form of cycloooxygenase (COX-2) than the constitutive form (COX-1). Inhibition of COX-1 is most commonly associated with deleterious gastric and renal effects.^3,6 In Canada, meloxicam is licensed for use in dogs at an initial dosage of 0.2 mg/kg once daily, followed by maintenance dosage at 0.1 mg/kg, and in humans at a total dose of 7.5 or 15 mg once daily.^1,2 The veterinary formulation is available as an injectable solution (5 mg/ml) or an oral solution (1.5 mg/ml) (Metacam, Boehringer Ingelheim, Burlington, Ontario, Canada, L7L 5H4), while the human formulation is oral tablets of 7.5 or 15 mg strength (Mobicox, Boehringer Ingelheim, Burlington, Ontario, Canada, L7L 5H4). To decrease volume of administration we have meloxicam compounded to a 5 mg/ml suspension by a compounding pharmacy in beef, banana and strawberry flavoured bases.

During the last few years at the Calgary Zoo meloxicam has been used extensively as the NSAID of choice in over 140 species ranging from amphibian and reptile species to bird and mammal species (Table 1). Clinical applications include management of surgical pain, treatment of suspected myalgia, and as supportive treatment in cases of injury, osteoarthritis, fever, illness, or cases of “ADR” (which we have coined “suspect meloxicam deficiency”). Meloxicam has been used for acute management such as perioperative pain control (1–7 days) as well as in the management of chronic pain over periods of weeks to months. One group of particular interest has been the exotic felids at the zoo—African lion (Panthera leo), Bengal tiger (Panthera tigris tigris), Canadian lynx (Lynx canadensis), cougar (Puma concolor), Siberian tiger (Panthera tigris altaica), and snow leopard (Uncia uncia). For acute pain management, we have found an initial dosage of 0.1–0.2 mg/kg either orally or subcutaneously, followed by oral dosage of 0.1 mg/kg every 24 hours for up to 5 days to be effective and well tolerated in these species. For cases of chronic pain, such as neoplasia or osteoarthritis, a dosage of 0.1 mg/kg orally three times weekly up to every 48 hours has been effective and well tolerated.

Table 1. Taxanomic groups in which meloxicam has been used at the Calgary Zoo

There have been two cases where meloxicam has been used over periods of weeks to months in large cats with no observed clinical side effects. In the first case, a 14-year-old, 190-kg male Siberian tiger was treated at a dosage of 0.1 mg/kg administered orally three times weekly for several weeks. This was in response to a diagnosed calcific tendonitis causing lameness in his left foreleg. Within 2 months, meloxicam was administered again at the same dosage every other day in response to a lameness associated with an aggressive chondrosarcoma of the right distal radius and carpus. While meloxicam treatment did improve the mobility and activity level of this tiger, more palliative treatment was required as the tumour progressed, and a better level of analgesia was obtained when codeine monohydrate-sulfate trihydrate (200 mg PO every 24 hours; Codeine Contin, Purdue Pharma, Pickering, Ontario, Canada, L1W 3W8) was added to his therapy. The tiger was observed to sleep more often, however, was much more fluid when moving on or off his sleeping platform or when ambulating while under this treatment. Other than the observed mild grogginess, there were no adverse reactions to the codeine such as excitement or constipation. When the decision to euthanatize was reached, there were no gross lesions associated with meloxicam administration in the gastrointestinal tract or the kidneys. Histopathology revealed lymphoid hyperplasia of the stomach mucosa with no evidence of ulcerative change. Age-related renal changes were observed, involving proteinaceous and fibrous accumulations in a few glomeruli, however, no tubular pathology which may have been associated with the use of an NSAID was noted.

The second case involves a mature, approximately 8-year-old, 170-kg white Bengal tiger which arrived at the Calgary Zoo in late October 2003. This animal presented with a moderate lameness of the right hindleg with associated pronounced muscle atrophy of the pelvic region; there was no history of any treatment or diagnostic information with regards to this lameness from the previous institution. On radiographs during his quarantine exam, there was moderate to marked osteodegenerative changes to the right femoral head and acetabular rim, with mixed osteophytic-osteolytic arthritic changes to the neck of the right femur. The left femoral head and acetabular rim had much milder changes with mild calcification of the tendon insertion points of pelvic-appendicular ligaments. Serum chemistry values were within normal limits. Initial management consisted of injections of a semi-synthetic polysaccharide (3.3 mg/kg SC every 7 days; Cartophen Vet, Arthropharm, Ottawa, Ontario, Canada, K1G 3Y6) and meloxicam (0.1 mg/kg PO three times weekly). Meloxicam therapy has continued for several months, and while some clinical improvement in the degree of lameness was noted, a pronounced limp was still apparent. Four months after the initiation of meloxicam, the tiger was anesthetized for a bone biopsy to rule out an infectious or neoplastic cause for the degenerative changes in his right femur. At this time, osteoproliferation of the right femoral neck was still apparent, with focal areas of radiolucency, however, there was a significant improvement seen when compared with the quarantine radiographs from November 2003. Osteophytic production of both hip joints was decreased, there was increased bone density of the femoral neck, and a cleaner edge to the acetabular rim. There also was decreased calcification of tendon insertion points on the left side. Serum chemistry values were within normal limits. Our conclusion was that by controlling the pain and inflammation associated with the osteoarthritis, there was a corresponding increase in activity and weight bearing on the hindlimbs, leading to bony remodeling and improved health of the coxofemoral joints in the intervening months.

Side effects are not common in canine species treated with meloxicam, with doses up to 5x the recommended dosage administered for 26 weeks not causing any clinical abnormalities. Suspected or potential adverse effects in dogs include gastrointestinal changes such as vomiting, diarrhea, inappetence, hematemesis, melena and ulceration, mild CNS or behavioural changes, elevated creatinine and blood urea nitrogen, dermatologic changes, elevations of liver enzymes, or immune-mediated anemia and thrombocytopenia.^2,4 In domestic cats, meloxicam has proved quite effective and safe for short term use in cats following surgery, for radiation induced stomatitis, or in treating painful locomotor disorders.^5,7-9 However, tolerance studies in cats resulted in the death of 2 of 12 cats after 8 days of treatment in the highest dose range (0.6 mg/kg SID) from duodenal ulceration and associated peritonitis, and after 9 days, all cats in the treatment groups had evidence of gastrointestinal ulceration. At lower doses, meloxicam was tolerated by cats, but the conclusion was drawn that the therapeutic index for meloxicam in cats is very narrow.⁴ Our experience with exotic felids is that short term or chronic use has not been associated with adverse side effects, however we still recommend close monitoring of biologic and haematologic parameters in all patients on meloxicam therapy.

Literature Cited

1.  Compendium of Pharamaceuticals and Specialties. 2003. Mobicox. Canadian Pharmacist Association. Pp1030–1033.

2.  Compendium of Veterinary Products. 2003. Metacam. Canadian Animal Health Institute. Pp 628–630.

3.  Del Tacca, M., R. Colucci, M. Fornai, and C. Blandizzi. 2002. Efficacy and tolerability of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory Drug. Clin Drug Invest 22(12):799–818.

4.  European Agency for the Evaluation of Medicinal Products. 2002. Metacam. http://www.emea.eu.int/vetdocs/vets/Epar/Metacam/Metacam.htm

5.  Lascelles, B.D., A.J. Henderson and I.J. Hackett. 2001. Evaluation of the clinical efficacy of meloxicam in cats with painful locomotor disorders. J. Small An. Pract. 42(12):587–593.

6.  Noble, S. and J.A. Balfour. 1996. Meloxicam. Drugs. 51(3):424–430.

7.  Slingsby, L.S. and A.E. Waterman-Earson 2000. Postoperative analgesia in the cat after ovariohysterectomy by use of carprofen, ketoprofen, meloxicam or tolfenamic acid. J. Small An. Pract. 41(10): 447–450.

8.  Slingsby, L.S. and A.E. Waterman-Earson 2002. Comparison between meloxicam and carprofen for postoperative analgesia after feline ovariohysterectomy. J. Small An. Pract. 43(7):286–289.

9.  Wallace, J. 2003. Meloxicam. Compend Contin Educ Pract Vet. 25(1);1:64–64.