Pharmacokinetic Profile of Fentanyl in the Koala (Phascolarctos cinereus) after Intravenous Administration, and Absorption via a Transdermal Patch

Fentanyl was administered as a single intravenous bolus injection at 5 µg/kg to five koalas and fentanyl plasma concentrations for a minimum of 2 h were quantified by an enzyme-linked immunosorbent assay (ELISA). The median (range) fentanyl elimination half-life and clearance were 0.53 (0.38–0.91) h, and 10.01 (7.03–11.69) L/kg/h, respectively. Assuming an analgesic therapeutic plasma concentration of 0.23 ng/mL (extrapolated from human studies), an intravenous constant infusion rate was estimated at approximately between 1.7 to 2.7 µg/kg/h (using the clearance 95% confidence intervals). A transdermal fentanyl patch was applied to the antebrachium of an additional two koalas for 72 h. Fentanyl plasma concentrations were determined during the patch application and after patch removal at 80 h. The fentanyl plasma concentration was greater than 0.23 ng/mL after 12 to 16 h. While the patch was applied, the maximum fentanyl concentration was approximately 0.7 ng/mL from 32 to 72 h. Fentanyl plasma concentrations increased to 0.89 ng/mL 1 h after the patch was removed, and then decreased to a mean of 0.47 ng/mL at 80 h. The transdermal fentanyl patch is likely to provide some level of analgesia but should be initially co-administered with another faster acting analgesic for the first 12 h.

Why are US military personnel prescribed transdermal fentanyl patches?

IntroductionTransdermal fentanyl is a continuous release opioid delivery system intended for use in opioid-tolerant patients requiring around-the-clock opioid therapy. The purpose of this study is to identify the most common indications for transdermal fentanyl prescriptions in active duty US military personnel, and determine whether these prescriptions meet US Food and Drug Administration (FDA) labelling.MethodsActive duty US military personnel initiating transdermal fentanyl therapy with prescriptions filled at Military Health System pharmacies between 2015 and 2019 were identified in the Military Data Repository. Electronic health records were searched for patient demographic information, clinical information and prescription data. A total of 225 patients with complete data were identified.ResultsThe most common reason for transdermal fentanyl initiation was chronic non-cancer musculoskeletal pain. Among patients with non-cancer pain, 36% received their initial prescription from an internal medicine/primary care provider, and 35% did not meet published US FDA criteria for opioid tolerance prior to treatment initiation. There was an 81% decrease in patients initiating therapy between 2015 and 2019.ConclusionsWhile a substantial minority of transdermal fentanyl prescriptions to US military personnel did not meet FDA guidelines on appropriate use, the overall number of prescriptions fell dramatically over the study period. This suggests that automated profile review or additional targeted policies to limit transdermal fentanyl prescribing are unnecessary at this time.

Opioids in patients with COPD and refractory dyspnea: literature review and design of a multicenter double blind study of low dosed morphine and fentanyl (MoreFoRCOPD)

Background Refractory dyspnea or breathlessness is a common symptom in patients with advanced chronic obstructive pulmonary disease (COPD), with a high negative impact on quality of life (QoL). Low dosed opioids have been investigated for refractory dyspnea in COPD and other life-limiting conditions, and some positive effects were demonstrated. However, upon first assessment of the literature, the quality of evidence in COPD seemed low or inconclusive, and focused mainly on morphine which may have more side effects than other opioids such as fentanyl. For the current publication we performed a systematic literature search. We searched for placebo-controlled randomized clinical trials investigating opioids for refractory dyspnea caused by COPD. We included trials reporting on dyspnea, health status and/or QoL. Three of fifteen trials demonstrated a significant positive effect of opioids on dyspnea. Only one of four trials reporting on QoL or health status, demonstrated a significant positive effect. Two-thirds of included trials investigated morphine. We found no placebo-controlled RCT on transdermal fentanyl. Subsequently, we hypothesized that both fentanyl and morphine provide a greater reduction of dyspnea than placebo, and that fentanyl has less side effects than morphine. Methods We describe the design of a robust, multi-center, double blind, double-dummy, cross-over, randomized, placebo-controlled clinical trial with three study arms investigating transdermal fentanyl 12 mcg/h and morphine sustained-release 10 mg b.i.d. The primary endpoint is change in daily mean dyspnea sensation measured on a numeric rating scale. Secondary endpoints are change in daily worst dyspnea, QoL, anxiety, sleep quality, hypercapnia, side effects, patient preference, and continued opioid use. Sixty patients with severe stable COPD and refractory dyspnea (FEV1 < 50%, mMRC ≥ 3, on optimal standard therapy) will be included. Discussion Evidence for opioids for refractory dyspnea in COPD is not as robust as usually appreciated. We designed a study comparing both the more commonly used opioid morphine, and transdermal fentanyl to placebo. The cross-over design will help to get a better impression of patient preferences. We believe our study design to investigate both sustained-release morphine and transdermal fentanyl for refractory dyspnea will provide valuable information for better treatment of refractory dyspnea in COPD. Trial registration NCT03834363 (ClinicalTrials.gov), registred at 7 Feb 2019, https://clinicaltrials.gov/ct2/show/NCT03834363.

Acute Cytotoxic Cerebellar Edema Subsequent to Fentanyl Patch Intoxication in an Infant

The opioid epidemic continues to have devastating consequences for children and families across the United States with rising prevalence of opioid use and abuse. Given the ease of access to these medications, accidental ingestion and overdose by children are becoming increasingly more common. The recognition of opioid-induced neurotoxicity and the associated life-threatening complication of acute cerebellar cytotoxic edema are crucial, as are the high morbidity and mortality without timely intervention. We discuss an infant with acute cytotoxic cerebellar edema following mucosal exposure to a transdermal fentanyl patch.

The Use of Thoracic Epidural for Rapid Opioid Taper

BACKGROUND: Inflammatory Bowel Disease (IBD) is often associated with significant abdominal pain that can be challenging to control. Although controversial, opioids are often prescribed for the management of abdominal pain in patients with IBD. There have been several methods described for the rapid taper of patients on long-term, high-dose opioids. However, to date, there have been no reported cases using epidural analgesia for rapid opioid taper. CASE REPORT: We present a case of a 36-year-old man with ulcerative colitis and recurrent bowel obstructions on a high-dose transdermal fentanyl patch whose opioid consumption was rapidly tapered during inpatient hospitalization utilizing thoracic epidural analgesia. CONCLUSION: The potential role of epidural analgesia in rapid opioid taper has yet to be explored. In patients with chronic pain and inflammatory bowel disease or recurrent bowel obstructions, epidural analgesia may be particularly helpful to improve gastrointestinal motility while also being used to rapidly taper opioid dosage. KEY WORDS: Inflammatory bowel disease, ulcerative colitis, Crohn’s disease, epidural, opioids, rapid opioid taper, fentanyl patch