Switching from Transdermal Drugs: An Observational “N of 1” Study of Fentanyl and Buprenorphine

Abstract

The aim of this study was to confirm that the concomitant presence of transdermal fentanyl (TTS FE) and buprenorphine (TTS BU) may be feasible without important consequences, using doses presumed to be equianalgesic. A prospective "N of 1" study was carried out in a sample of volunteers with cancer pain receiving stable doses of TTS FE or TTS BU, with adequate pain and symptom control. In the study design, each patient provided data before and after a switch from one opioid to the other and then back to the previous one. Sixteen patients receiving daily stable doses of 0.6 or 1.2mg of TTS FE were switched to TTS BU using an FE-BU ratio of 0.6-0.8. After three days, the TTS BU patch was removed and TTS FE patch was placed for another three days. Six patients receiving TTS BU were switched to TTS FE and then rotated back to TTS BU with the same dosing considerations. No statistical differences in changes in pain and symptom intensity during switching and between the two different sequences were observed. No significant changes in rescue doses of oral morphine were reported at the same intervals. Cancer patients receiving stable doses of TTS FE or TTS BU can be safely switched to the alternative transdermal opioid. Further studies should be performed to gather data about the use of TTS BU with other opioids, at different doses, and in different clinical conditions.

Managing severe cancer pain: the role of transdermal buprenorphine: a systematic review

“…The main characteristics of the remaining 19 papers [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] are reported in Table 1. The 19 published articles described 16 different studies: Radbruch 29 presented the aggregated data from Bohme, 28 Sittl, 31 and Sorge; 32 Evans reported efficacy and safety data by pooling the 3 placebo-controlled RCTs; 25 and Radbruch 30 and Apolone 35 reported the preliminary information later published by Griessinger 33 and Apolone, 46 respectively.…”

“…The 19 published articles described 16 different studies: Radbruch 29 presented the aggregated data from Bohme, 28 Sittl, 31 and Sorge; 32 Evans reported efficacy and safety data by pooling the 3 placebo-controlled RCTs; 25 and Radbruch 30 and Apolone 35 reported the preliminary information later published by Griessinger 33 and Apolone, 46 respectively. Nine were clinical trials 28,31,32,37,[39][40][41][42]44 and 7 were observational (non-intervention) studies. 33,34,36,38,43,45,46 Most of the papers reported data from a mixed population including both cancer and non-cancer patients (12/19).…”

“…Three experimental studies were subsequently excluded because they were early-phase feasibility trials: a rotation feasibility trial describing cross-over administration of two drugs, 41 a pilot study describing the effect of pre-planned rotation administration of several drugs, 39 and a dose escalation administration trial. 37 The characteristics of the remaining 6 studies, 28,31,32,40,42,44 involving 499 cancer patients (range 9 to 189) are reported in Table 2A.…”

Equipotent doses to switch from high doses of opioids to transdermal buprenorphine

“…The results of this study, in which oral morphine or TS fentanyl at relatively higher doses were switched to presumed equianalgesic doses of TS BUP, confirm preliminary observations of an "n of 1" study of cancer patients receiving lower stable doses of TD fentanyl or BUP (25 and 50 µg/h versus 35 and 70 µg/h, respectively). Patients could be safely switched to the alternative transdermal opioid by using a ratio of 0.6:0.8, corresponding to a ratio of 70:1 with oral morphine [8], maintaining the same level of analgesia.…”

“…In another study of volunteers who were switched from fentanyl to BUP and vice versa, according to an indirect conversion TD fentanyl-oral morphine, the approximate equianalgesic ratio between oral morphine and TD BUP resulted to about 1:70 [8]. In contrast, other different studies suggest an equipotency ratio of about 1:110 [3,5,9,10], which means much lower doses than anticipated.…”