Naloxone reversal of an overdose of a novel, long‐acting transdermal fentanyl solution in laboratory Beagles

Abstract

Freise, K. J., Newbound, G. C., Tudan, C., Clark, T. P. Naloxone reversal of an overdose of a novel, long-acting transdermal fentanyl solution in laboratory Beagles. J. vet. Pharmacol. Therap. 35 (Suppl. 2), 45-51.Opioid overdose in dogs is manifested by clinical signs such as excessive sedation, bradycardia, and hypothermia. The ability of two different intramuscular (i.m.) naloxone reversal regimens to reverse the opioid-induced effects of a fivefold overdose of long-acting transdermal fentanyl solution was evaluated in dogs. Twenty-four healthy Beagles were administered a single 13 mg ⁄ kg dose (fivefold overdose) of transdermal fentanyl solution and randomized to two naloxone reversal regimen treatment groups, hourly administration for 8 h of 40 (n = 8) or 160 lg ⁄ kg i.m. (n = 16). All dogs were sedated and had reduced body temperatures and heart rates (HRs) prior to naloxone administration. Both dosage regimens significantly reduced sedation (P < 0.001), and the 160 lg ⁄ kg naloxone regimen resulted in a nearly threefold lower odds of sedation than that of the 40 lg ⁄ kg i.m. naloxone regimen (P < 0.05). Additionally, naloxone significantly increased the mean body temperatures and HR (P < 0.001), although the 160 lg ⁄ kg regimen increased body temperature and HR more (P < 0.05). However, the narcotic side effects of fentanyl returned within 1-3 h following termination of the naloxone dosage regimens. The opioid-induced effects of an overdose of transdermal fentanyl solution can be safely and effectively reversed by either 40 or 160 lg ⁄ kg i.m. naloxone administered at hourly intervals.(Paper

Population pharmacokinetics of transdermal fentanyl solution following a single dose administered prior to soft tissue and orthopedic surgery in dogs

“…Two additional samples from two different dogs were excluded from the analysis that were >15 ng/mL, but were not associated with profound or greater sedation. These samples were judged to be spurious based on previous studies where 100% dogs exhibited profound or greater sedation above this plasma concentration (Freise et al. , 2012; Savides et al , 2012).…”

Analgesia in the Perioperative Period

“…11,12 It should also be noted that the opioid antagonist naloxone was able to reverse the effects of overdose when administered at hourly intervals. 13 Because this product is approved for dogs and reduces the chance for accidental human exposure, it is recommended that it be used in place of the commercially available human transdermal patches. …”

The present and future of opioid analgesics in small animal practice

“…An issue of the Journal of Veterinary Pharmacology and Therapeutics was published in June 2012 with studies on the safety, efficacy, and PK‐PD of Recuvyra ® in dogs (Freise et al ., ,b,c,d; KuKanich & Clark, ; Linton et al ., ; Riviere, ; Savides et al ., ). The drug is applied to the skin 2–4 h before surgery and may provide analgesia after single application for up to 4 days postadministration (KuKanich & Clark, ).…”