Randomized 5‐Treatment Crossover Study to Assess the Effects of External Heat on Serum Fentanyl Concentrations During Treatment With Transdermal Fentanyl Systems

This randomized, open‐label, 5‐treatment, 5‐sequence crossover study was designed to evaluate the effects of a heating pad on serum fentanyl concentrations with reservoir and matrix transdermal fentanyl systems. Subjects were randomized to 1 of 5 treatment sequences, receiving 5 fentanyl treatments (1 per period) for 36 hours: 25 μg/h reservoir without heat, 25 μg/h reservoir with heat, 25 μg/h matrix without heat, 25 μg/h matrix with heat, and a 50 μg/h reservoir without heat. The 25 μg/h systems with heat had a heating pad applied from 0 to 10 and 26 to 36 hours post application. Washout periods between treatments were 5 to 14 days. Naltrexone was given to block the opioid effects of fentanyl. Study results indicate that external heat had a similar effect on both matrix and reservoir systems, with heat applied during the first 10 hours of treatment increasing fentanyl exposure by approximately 61% to 81% at 10 hours (observed serum concentration at 10 hours) and overall exposure (area under the curve from 0 to 10 hours) by approximately 120% to 184%, but had minimal effect from 26 to 36 hours. The increased exposure observed with heat in both 25 μg/h systems, between 0 and 10 hours, was higher than that obtained with the 50 μg/h reservoir system applied without heat.