An Iontophoretic Fentanyl Patient-Activated Analgesic Delivery System for Postoperative Pain: A Double-Blind, Placebo-Controlled Trial

Abstract

An iontophoretic fentanyl HCl patient-activated transdermal system (fentanyl HCl PATS) is under development for the treatment of acute postoperative pain. The fentanyl HCl PATS is a needle-free, credit card-sized, preprogrammed system that is applied to the patient's upper outer arm or chest. The fentanyl HCl PATS was demonstrated to be superior to placebo in a previous trial; however, the randomization scheme used and the lack of control of entry pain level may have contributed to the lack of robust findings. We compared the fentanyl HCl PATS with placebo for acute postoperative pain management in a larger trial that addressed the limitations of the previous study. Adult patients admitted to the postanesthesia care unit after major surgery were titrated to comfort with opioids and randomized 1:1 to receive the fentanyl HCl PATS 40 microg or placebo for 24 hours. Supplemental IV fentanyl was available to patients upon request in both treatment groups for the first 3 hours after enrollment. The primary efficacy end-point was the percentage of patients who discontinued participation in the study because of inadequate analgesia. Pain intensity scores, patient global assessments (PGA), and investigator global assessments (IGA) were collected. Four-hundred-eighty-four patients (PATS, n = 244; placebo, n = 240) were enrolled. Fewer patients receiving the fentanyl HCl PATS discontinued because of inadequate analgesia compared with placebo (28.7% versus 60.0%; P < 0.0001). Mean last pain intensity scores were 3.5 and 5.4 for the fentanyl HCl PATS and placebo groups, respectively. Patients (73.4%, PGA) and investigators (72.1%, IGA) considered the fentanyl HCl PATS a good or excellent method of pain control. Treatment-related adverse events were similar between groups. This study demonstrated the superiority of the iontophoretic fentanyl HCl PATS over placebo for acute postoperative pain management.

Pharmacokinetic characteristics of fentanyl iontophoretic trandermal system over a range of applied current

“…Therefore, these data demonstrate that the modifications made to the original fentanyl ITS did not significantly affect the amount of fentanyl absorbed and that standard bioequivalence criteria [15] were achieved. The original fentanyl ITS was utilized in the Phase III studies that demonstrated that fentanyl ITS was superior efficacy to placebo [9,14] and has therapeutically equivalent efficacy to morphine administered i.v. as patient-controlled analgesia in adult patients with acute post-operative pain [10][11][12][13].…”

“…Phase III trials were performed with the original fentanyl ITS for treatment of acute postoperative pain in adult patients during hospitalization [9][10][11][12][13][14]. Patients were treated with the fentanyl ITS for up to 3 days after their operation.…”

Uso do fentanil transdérmico para analgesia pós-operatória em cirurgia de artrodese de coluna

“…A natureza não invasiva do método minimiza as complicações relacionadas à agulha e a punções venosas, além de também eliminar o risco de intervalos na analgesia, o que é inerente aos métodos não contínuos 12 . Uma preocupação importante relativa à analgesia aguda com opioides é a possibilidade de insuficiência respiratória, entretanto estudos comprovam a segurança do fentanil transdérmico para esses pacientes 6,[13][14][15] . Estudo demonstrou que o uso de fentanil por via transdérmica proporcionou analgesia satisfatória com baixas intensidades de dor.…”

“…Procedimentos cirúrgicos como artrodese de coluna são sabidamente acompanhados de grande potencial doloroso, e o fentanil transdérmico mostrou ser um grande aliado na analgesia desses pacientes. 6,17 . Algumas vantagens são a praticidade de administração do adesivo, a não dependência de acesso venoso ou de pessoal treinado em bombas de analgesia.…”

“…Um dos fatores que contribuem para a inadequada analgesia é a ocorrência de dor nos intervalos entre a administração de doses de analgésicos e os efeitos adversos 3 . O fentanil administrado por via transdérmica, que apresenta farmacocinética similar ao uso por via venosa com a concentração plasmática se mantendo constante durante o período de até 72 horas 4 , tem se mostrado um método seguro e efetivo no manuseio da dor crônica, e também tem sido usado para promoção de analgesia também na dor aguda 5,6 . O objetivo deste estudo foi avaliar a analgesia proporcionada pelo uso do fentanil transdérmico na dor aguda pós-operatória em pacientes submetidos à cirurgia de artrodese de coluna, bem como observar a incidência de efeitos adversos relacionados ao seu uso.…”