Page 568 - WSAVA2018
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 25-28 September, 2018 | Singapore
were measured 3 hours after the first dose and last dose (14 day). The plasma concentrations of carprofen were within the expected plasma concentrations. The plasma concentrations of tramadol were low (39.3 _ 35.3 ng/
mL) 3 hours after the first dose and were significantly decreased 3 hours after the last dose (7.1 _ 8.8 ng/mL), and not even detected in 4 of 11 dogs, again suggesting decreased bioavailability with multiple doses. In contrast, a recent randomized, blinded, placebo-controlled crossover study investigating the effectiveness of tramadol for the treatment of pain due to osteoarthritis of the elbow or stifle joint in dogs concluded that following 10 days of treatment with tramadol (administered 5 mg/ kg, PO, q8h) provided no clinical benefit.(18) The most likely reason for this disparity is the method of Canine Brief Pain Inventory (CBPI) data evaluation and the definition of treatment response in each study. In the study by Malek et al. (2012), absolute change in overall CBPI score was used as the outcome measurement; however, in the study by Budsberg et al. (2018), a positive treatment response was defined as a score reduction
≥ 1 for pain severity score and ≥ 2 for pain interference
score. In the study by Malek et al. (2012), overall CBPI
score was the only outcome variable measured to
evaluate response to tramadol administration. The data
evaluation methodology utilized by Budsberg et al. (2012)
is regarded by many to be the more accurate approach. (19)
Although more long-term controlled clinical studies
are still needed in cats, the available evidence would suggest that tramadol maybe more efficacious for the treatment of chronic pain in this species than in dogs. A prospective, randomised, blinded, placebo-controlled, crossover study by Monteiro et al. (2017) found that treatment with tramadol increased weight-bearing, mobility and decreased central sensitisation in cats with naturally occurring osteoarthritis.(20) This study reported that tramadol therapy of up to 19 days (3 mg/kg orally) seems safe in cats, with the most common adverse side-effects being mydriasis, sedation and euphoria. These results are encouraging for promoting tramadol as a treatment for pain in osteoarthritic cats and are further supported by a 2018 published randomised controlled crossover trial by Guedes and colleagues which reported that that twice-daily oral administration of tramadol at a dosage of 2 mg/kg for five days produced detectable improvements in measures of mobility in geriatric cats, with a positive impact on cats’ quality of life according to owners.(21) Clinically, because there were dose-dependent adverse events, most frequently manifested as behavioural changes, decreased appetite, and diarrhoea, additional dosage refinement may be necessary in individual cats, aiming to balance efficacy and tolerability.
· There is growing evidence to support the use of tramadol for the treatment of pain in cats in both the perioperative period and cats with chronic osteoar- thritis.
· A high degree of intersubject variability and inter- study variability has been demonstrated in the dog with respect to the pharmacokinetics and analgesic efficacy of tramadol. Due to the high degree of breed and individual variation in analgesic efficacy of trama- dol in dogs it should not be utilised as a first-line or sole analgesic drug in this species.
Cats: Most current recommendations for dosing in cats are 1 – 2 mg/kg PO q12h. Some suggest that some cats may only need once daily doses; others suggest going as high as 4 mg/kg. Perioperative doses of 2 mg/kg
IV and 4 mg/kg IM in clinical studies are documented in cats, while doses of 3 to 4 mg/kg IV have been administered during thermal threshold studies.
Dogs: Dogs may benefit from tramadol administered
4 – 10 mg/kg PO q 6-12 h. Maximum analgesic effects may not occur immediately and may be delayed up
to 14 days for chronic pain conditions such as cancer and degenerative joint disease. Long-term efficacy of tramadol (particularly opioid actions) may decrease with time. Perioperative doses of 2 mg/kg IV, are documented in dogs.
Side effects are considered rare but may include: Transient signs of nausea, emesis, salivation, pupil constriction and panting (dogs) may occur. Cough suppression, decreased heart rate and constipation may result but should not be clinically significant. Overdose may manifest as seizures, pinpoint pupils, and mental alterations.
Potential drug interaction that should be considered: Tramadol is not compatible (or may require dose reduction) with other psychoactive drugs such as serotonin reuptake inhibitors, tricyclic antidepressants, or monoamine oxidase inhibitors. Tramadol can induce sedation when combined with amitraz, the active ingredient in many tick control products. Concurrent use of tramadol and cyproheptadine, an appetite stimulant, can reduce the effect of the tramadol. A human product called Ultracet® is available. It contains acetaminophen (paracetamol) in addition to tramadol. This product is NOT safe for cats. If discontinuing tramadol after long- term use, dose tapering is recommended.

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