Clinical safety of robenacoxib in cats with chronic musculoskeletal disease.

BACKGROUND: Evaluate the clinical safety of robenacoxib in cats with chronic musculoskeletal disease (CMSD). ANIMALS: Four hundred forty-nine client-owned cats with CMSD. METHODS: Pooled analysis of safety variables from 4 prospective randomized blinded clinical trials of robenacoxib (n = 222) versus placebo (n = 227), administered orally once daily for 4 to 12 weeks. Safety was evaluated from reported adverse events (AEs) and abnormalities detected on hematology and serum and urine chemistry analyses. RESULTS: The number of cats with at least 1 AE was not significantly different (P = .15) with robenacoxib (n = 106, 47.8%) compared to placebo (n = 93, 41.0%). The relative risk of at least 1 AE (incidence robenacoxib/placebo) was 1.15 (95% confidence interval 0.93-1.43). There was no significant difference between groups in the number of clinical signs (range, 0-9) per cat (P = .23). Serum creatinine concentrations were higher during robenacoxib administration compared to placebo (+4.36 µmol/L, 95% confidence interval 0.21-8.50), but no related adverse clinical effects were detected. In the subgroup of 126 cats with evidence of chronic kidney disease, the relative risk of at least 1 AE (robenacoxib/placebo) was 1.09 (95% confidence interval 0.78-1.52, P = .61). CONCLUSIONS AND CLINICAL IMPORTANCE: Robenacoxib was not associated with increased risk of AEs compared to placebo when administered for 4 to 12 weeks to cats with CMSD. The generalizability of the results to general practice is limited by the fact that cases with severe and uncontrolled concomitant diseases were not included.

Efficacy and safety of oral robenacoxib (tablet) for the treatment of pain associated with soft tissue surgery in client-owned dogs.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have been proven to be effective in controlling peri-operative pain in dogs. Robenacoxib is an NSAID with high selectivity for the cyclooxygenase (COX)-2 isoform. The objective of this study was to assess the efficacy and safety of an oral tablet formulation of robenacoxib in client-owned dogs undergoing soft tissue surgery. The study was a prospective, multi-center, randomized, masked, placebo-controlled, parallel-group clinical trial. A total of 239 dogs were included and randomly allocated in a 1:1 ratio to receive either robenacoxib or placebo. Each dog received an oral tablet administration of either robenacoxib, at a target dose of 2 mg/kg, or placebo once prior to surgery and for two additional days post-operatively. All dogs also received a pre-anesthetic dose of 0.2 mg/kg butorphanol (intravenous or intramuscular). Pain assessments were performed using the short form of the Glasgow Composite Measure Pain Scale. Robenacoxib was compared to the placebo group on a success/failure basis. Treatment failure was defined as the need for rescue therapy to control post-operative pain. RESULTS: Significantly (P = 0.019) more dogs administered robenacoxib were considered treatment successes (89 of 116, 76.72%) compared to dogs given placebo (74 of 115, 64.35%). The percentage of treatment failure was therefore 23.28% in the robenacoxib and 35.65% in the placebo group. The least squares mean total pain scores were significantly different between groups and in favor of robenacoxib at 3 and 5 hours (P < 0.05) and 8 hours post-extubation (P < 0.01). Pain at the surgery sites (response to touch) was also significantly improved at 3, 5 and 8 hours post-extubation in dogs receiving robenacoxib versus placebo (P < 0.01). In addition, a significant overall improvement in posture/activity was revealed with robenacoxib having lower scores versus placebo (P < 0.01). No significant differences between the robenacoxib and placebo groups in the frequency of reported adverse events were observed. CONCLUSIONS: Robenacoxib by oral (tablet) administration was effective and well tolerated in the control of peri-operative pain and inflammation associated with soft tissue surgery in dogs.

Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.

BACKGROUND: Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo (control group), benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all groups received in addition 0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days. RESULTS: Benazepril, robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs and no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables. The primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma clearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of benazepril plus robenacoxib compared to the other three groups, and was also significantly higher in females receiving only benazepril compared to the control. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system, evidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group in cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by robenacoxib (males only). Benazepril, robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by furosemide. CONCLUSIONS: The combination of benazepril and robenacoxib was well tolerated and either increased or had a neutral effect on GFR in healthy cats without or with concomitant furosemide. The combination of benazepril and robenacoxib reduced plasma aldosterone concentrations increased by furosemide. It is recommended to test the efficacy and safety of the combined use of benazepril and robenacoxib in cats with clinical disease, notably proteinuric chronic kidney disease.

Effects of periparturient systemic treatment with penethamate hydriodide on udder health and milk yield of dairy heifers.

Sixty dairy heifers from seven Austrian herds, with high prevalence of Staphylococcus aureus mastitis, were used in this pilot study. Heifers were randomly allocated to two groups. The treatment group received at parturition intramuscularly 10 million i.u. of penethamate hydriodide and then 24 h later, 5 million i.u.; the control group received no treatment. Bacteriological examination was conducted on 7, 14, 21, 35 and 49 d post partum (pp) and milk yield data, fat and protein contents and SCC data were collected every 5th week for the first 200 d of lactation. Occurrence of retained placenta and endometritis were recorded, and the days open of both groups were compared. No effect was observed on the postparturient genital tract health and reproduction indicators. On day 7 pp, four intramammary infections (IMI; two severe clinical; one mild clinical; and one subclinical mastitis) were detected in the untreated control group, whereas there were no IMI in the antibiotic-treated group. At subsequent samplings, there were fewer IMI in the antibiotic-treated group, which were later in lactation, less severe and less persistent. Although SCC was numerically lower in the treatment group, significant differences in SCC between groups could not be detected. Antibiotic-treated heifers produced significantly more milk during the first 15 weeks of lactation than untreated heifers. Over the whole observation period (200 d), peripartum antibiotic-treated heifers produced 323 kg more milk than heifers in the untreated control. Periparturient antibiotic treatment of heifers with penethamate hydriodide prevented IMI during the first week after parturition and achieved a significant increase in milk yield, which was found to be economically beneficial.

Effect of steroidal and non-steroidal anti-inflammatory drugs on inflammatory markers in calves with experimentally-induced bronchopneumonia.

The influence of treatment with steroidal (SAIDs) and non-steroidal (NSAIDs) anti-inflammatory drugs on inflammatory markers in thirty, 6-8 week old calves with induced bronchopneumonia was investigated. Animals received a single intravenous treatment with meloxicam (0.5 mg/kg body weight), flumethasone (0.05 mg/kg body weight) or sterile 0.9% NaCl (10 ml per animal). Body temperature, respiratory and heart rate, concentration of prostaglandins PGE2, PGF2alpha, thromboxane (TXB2), leukotriene (LTB4) and malonyldialdehyd (MDA) and proinflammatory cytokines i.e. tumor necrosis factor (TNFalpha) and interferon (INFalpha) were recorded in serum, bronchoalveolar lavage (BAL) and blood platelets (BP). A significant reduction of main inflammatory mediators PGE2, PGF2alpha,TXB2 and MDA after meloxicam treatment in calves with induced bronchopneumonia indicates a beneficial effect on the inflammatory processes. Contrary to effects observed by flumethasone, meloxicam induced an increase of LTB4 and INFalpha indicating that it is not immunosuppressive.

Clinical efficacy of meloxicam (Metacam) and flunixin (Finadyne) as adjuncts to antibacterial treatment of respiratory disease in fattening cattle.

The clinical efficacy of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam (Metacam 20 mg/ml) and flunixin meglumine (Finadyne), as adjuncts to antibacterial therapy in the treatment of acute febrile respiratory disease in cattle was compared. The randomised blind, positive controlled study was conducted under feedlot conditions in Mexico. Overall, 201 female cattle (weighing 220-250 kg) diagnosed with bronchopneumonia at the feedlot were recruited into the study. On Day 0 all animals were treated with 20 mg oxytetracycline/kg body-weight (Bivatop 200) by subcutaneous injection, in conjunction with either meloxicam (0.5 mg/kg subcutaneously, Metacam 20 mg/ml, n = 100), or flunixin meglumine (2.2 mg/kg intravenously, Finadyne, n = 101). According to label instructions, meloxicam was administered as a single dose, whereas flunixin meglumine could be administered daily for up to 3 consecutive days depending on the rectal temperature (with re-administration, if rectal temperature > or = 40.0 degrees C). Rectal temperature, respiratory rate, appetite, dyspnoea, coughing, nasal discharge and general condition were recorded on Days 0 (prior to treatment), 1, 2, 3 and 7 using a weighted numerical score. Scores were summed to generate a 'Clinical Sum Score' (CSS, range 7 to 24 points). Individual animal body weights were measured on Days 0 and 7. Nasal swabs were collected from 10 animals per treatment group on Day 0 for microbiological culture. Clinical parameters and the mean CSS showed no significant differences between treatment groups with mean CSS on Days 0 and 7 of 16.18 and 10.55 in the meloxicam group and 16.41 and 10.88 in the flunixin meglumine group. However, a significantly lower mean rectal temperature was measured in the meloxicam group on Day 2 (p < or = 0.01). No significant differences in mean body weights were found between groups. Repeated administration of flunixin meglumine was performed in 45% of the animals. No suspected adverse drug events related to treatments were reported. It is concluded that a single subcutaneous dose of meloxicam was as clinically effective as up to 3 consecutive daily intravenous doses of flunixin meglumine when used as an adjunctive therapy to antibacterial therapy in the treatment of acute febrile respiratory disease in feedlot cattle.

Investigation on the clinical efficacy and safety of meloxicam (Metacam) in the treatment of non-infectious locomotor disorders in pigs.

The clinical efficacy and safety of meloxicam (Metacam 20 mg/ml) in the treatment of non-infectious locomotor disorders in pigs was investigated in a randomised double-blind, placebo controlled, multi-centre field study. A total of 220 pigs were examined, 211 pigs were suitable for evaluation. Treatment was performed on Day 1 with meloxicam (0.4 mg meloxicam/kg) or placebo by intramuscular injection. If necessary, treatment was optionally repeated on Day 2. Clinical examinations were conducted daily from Day 1 (immediately prior to initiation of therapy) to Day 4. The primary parameter, mean "Clinical Lameness Score" (CLS, a sum of the scores of "Lameness at Rest" and "Lameness at Walk"; range 2 to 11) improved from 6.8 and 6.3 on Day 1, to 3.5 and 4.7 on Day 4 in the meloxicam and placebo groups respectively (p < 0.001). At the final examination mean changes from baseline for CLS (Day 1) were 3.25 for meloxicam treated animals and 1.7 for placebo treated animals (p < 0.001). Behaviour score and feed intake improved during the study period with statistically significant differences in favour of meloxicam at all time points after initiation of therapy. Significantly fewer pigs received a second treatment in the meloxicam group than in the placebo group, 46% versus 73% (p < 0.001). A 'very good' or 'good' clinical efficacy assessment was recorded in 83% of the meloxicam cases compared to 42% of the placebo controls at the final examination (p < 0.001). No adverse events were reported due to the use of meloxicam. Furthermore safety of meloxicam in pregnant sows was demonstrated. It is concluded that intramuscular injection of meloxicam (Metacam) at a dosage of 0.4 mg/kg is efficacious and safe for the treatment of non-infectious locomotor disorders in pigs.