Six-month safety evaluation of robenacoxib tablets (Onsior™) in dogs after daily oral administrations

Abstract

BackgroundRobenacoxib is a non-steroidal anti-inflammatory drug available for canine and feline use for the control of pain and inflammation marketed as Onsior™. The aim of this target animal safety study was to evaluate the 6-month safety profile of oral robenacoxib administration. It was a randomized, negative-controlled, parallel group study. Thirty-two healthy, young, experimentally naïve, purebred Beagle dogs were administered 0 (sham control, Group 1), 2, 6, and 10 mg/kg robenacoxib (corresponding to the upper end of the dosage range [1X, Group 2] and multiples thereof [3X and 5X, Group 3 and 4]), orally once daily for 6 months. Assessment of safety included general health and clinical observations, physical, neurological, ophthalmological and electrocardiographic examinations, gross and histopathological examinations and clinical pathology evaluations. Blood samples were collected for toxicokinetic assessment of robenacoxib.ResultsNo serious adverse events were reported. When compared with control, no treatment effect was observed for body weight, feed or water consumption, clinical pathology, urinalysis and fecal examination parameters. There were no treatment-related changes in stifle joint tissues and microscopic/histopathology examinations of all tissues/organs were normal. Salivation and soft feces were noted in all groups but observed more frequently in the treated groups as compared with control. On Day 178, increased buccal mucosal bleeding times were observed in two treated animals (Group 3 and 4) and one dog in Group 4 displayed a retinal change. Decreased hopping and conscious proprioception was noted in four treated dogs. One dog in Group 2 had ventricular premature complexes. Post-mortem changes included mild, red foci on the cecum in one dog (Group 3) and minimal duodenal discoloration in one dog (Group 4), with no corresponding histological findings in either dog. Ovarian weights were decreased in females from Group 3 and 4 with no gross or histological changes in the ovaries. Blood concentrations of robenacoxib confirmed systemic exposure of treated dogs. Exposure increased with increasing doses and there were no accumulation of robenacoxib in blood.ConclusionsRobenacoxib was well tolerated at doses from 2 to 10 mg/kg/day and this 6-month study supports the safe use of Onsior™ (robenacoxib) tablets in dogs for the intended dosing regimen.

Evaluation of the Effects of Undenatured Type II Collagen (UC-II) as Compared to Robenacoxib on the Mobility Impairment Induced by Osteoarthritis in Dogs

“…At the time of OA diagnosis (T0), all the patients were randomly (excel-based system) assigned to 2 groups that received a different pharmacological treatment: Group R = robenacoxib (Onsior ® ) 1 mg/kg/day orally (OS) for 30 days [18,19] and group UCII = UC-II (Flexadin ® Advanced) 1 tablet (40 mg) per day OS for 30 days [3,20,21,22]. Owners were instructed to give the dose at approximately the same time each day, without food and at least at one hour from the next meal.…”

“…Robenacoxib belongs to the new generation of NSAIDS characterized by a high selectivity for the cyclo-oxygenase (COX)-2 enzyme (COXIB) [14,15]. It is a drug developed solely for companion animal use with several properties of interest for use in dogs: it has a fast onset and the availability of both injectable and oral formulations; it is cleared from the central body compartment, but persists at the site of inflammation (tissue selectivity) [16,17] and it has less side effects than others non-selective NSAIDs [18]. In the European Union, robenacoxib is registered for the treatment of pain and inflammation associated with OA and surgery in dogs, showing safety also for long-term use, at the dosage of 1–2 mg/kg [18,19].…”

Pharmacology, safety, efficacy and clinical uses of the COX‐2 inhibitor robenacoxib

“…These findings were confirmed after administration of the flavoured tablet formulation of robenacoxib (0, 2, 6, and 10 mg/kg once daily for six months) to Beagle dogs. There were no demonstrable adverse effects on body weight, feed and water consumption, urinalysis, faecal examination and stifle joint tissues (Toutain et al, 2018). Clinical pathology data indicated only increased eosinophil count (10 mg/kg) and reduced ovary weight (6 and 10 mg/kg).…”

Enflicoxib for canine osteoarthritis: A randomized, blind, multicentre, non-inferiority clinical trial compared to mavacoxib

“…The management of OA in dogs is a lifetime commitment, involving a multimodal approach based on relieving the symptoms of the disease by treating pain and inflammation, improving mobility and hence quality of life, whilst protecting joints from OA [ 11 – 15 ]. Non-steroidal anti-inflammatory drugs (NSAIDs) have been the medical cornerstone for the management of pain and inflammation in canine OA for many years [ 16 , 17 ] and preferential and selective cyclooxygenase-2 (COX-2) inhibitors have been developed to potentially reduce the risk of unwanted side effects caused by the inhibition of COX-1 [ 18 , 19 ]. Further to classic NSAIDs therapy, newly registered products such as grapiprant and bedinvetmab have also shown efficacy in the control of pain associated to OA [ 20 , 21 ].…”