Adverse reactions to fentanyl transdermal patches in calves: a preliminary clinical and pharmacokinetic study

Abstract

Objective: To describe adverse reactions and measure plasma fentanyl concentrations in calves following administration of a fentanyl transdermal patch (FTP).

Study design: Prospective, experimental clinical study.

Animals: Six female Holstein calves and one male Angus calf. Four calves were healthy experimental animals and three calves were clinical patients.

Methods: Plasma fentanyl concentrations were measured in blood collected from a jugular vein. FTP 2 μg kg^-1 hour^-1 and 1 μg kg^-1 hour^-1 was applied to four and three calves, respectively. Heart rate, respiratory rate, temperature and ataxia were recorded at the same times as blood collection (0, 2, 4, 6, 12, 24, 36, 48, 60, 72, 84 and 96 hours). Substance P concentrations were determined via radioimmunoassay for two calves.

Results: After the FTP (2 μg kg^-1 hour^-1) application, two calves developed tachycardia, hyperthermia, excitement and ataxia within 6 hours; no adverse effect was observed in the other two calves. The three calves administered FTP (1 μg kg^-1 hour^-1) exhibited tachycardia and excitement, and the FTP were removed at 4 hours. Naloxone was administered to two calves before the adverse clinical signs ceased, while adverse events in the other three calves resolved within 2 hours of FTP removal. Variables returned to previous baseline values by 2-4 hours after FTP removal. Maximum plasma fentanyl concentrations were variable among calves (0.726-6.923 ng mL^-1). Substance P concentrations measured in two calves were not consistently depressed during FTP application. Fentanyl concentrations at 4 and 6 hours were significantly associated with the appearance of adverse effects.

Conclusions and clinical relevance: FTP (1-2 μg kg^-1 hour^-1) administered to calves may result in adverse behavioral and cardiovascular effects. Patch removal and treatment with an opioid antagonist may resolve these adverse effects. Additional research is needed to determine optimal FTP dosing for cattle.

Keywords: adverse event; calf; fentanyl; fentanyl transdermal patch.