Transdermal Fentanyl as A Front-Line Approach to Moderate-Severe Pain: A meta-analysis of Randomized Clinical Trials

Abstract

Objective: The safety of transdermal fentanyl (TF) in comparison with slow-release oral morphine (SROM) in moderate-severe pain was assessed. Design: A systematic review of the literature was performed to identify all randomized trials comparing TF and SROM in moderate-severe pain. Overall safety was the primary end point. Trials enrolling both cancer and non-cancer patients were included in the analysis. Heterogeneity was assessed using the Mantel-Haenszel test; a random effects model was used for the pooled analysis. Cumulative and distinctive analyses for cancer and non-cancer pain were performed whenever the outcome was reported in at least two trials. Results: Five trials met the inclusion criteria. A significant advantage of TF was documented for constipation, laxative use, and urinary retention. TF was preferred by cancer and non-cancer patients. A difference in favour of SROM was documented for nausea, diarrhea, and sweating in cancer and non-cancer patients. No differences were observed for the other items considered. Conclusions: TF and SROM seem to have a different side effects profile, and TF seems to be preferred by patients. The hierarchical approach traditionally recommended by the main scientific societies (oral morphine and then TF) could be replaced by a front-line approach based on patients’ characteristics and needs.

Efficacy and adverse effects of transdermal fentanyl and sustained-release oral morphine in treating moderate-severe cancer pain in Chinese population: a systematic review and meta-analysis

“…Similar with European and American data [4-6], our data also showed that both transdermal fentanyl and sustained-release oral morphine were effective in treating stable moderate-severe cancer pain in Chinese population with less adverse effects for transdermal fentanyl. However, two differences should be pointed out.…”

“…Three systematic reviews of European and American literatures suggested both transdermal fentanyl and sustained-release oral morphine could effectively control moderate-severe cancer pain, but some adverse effects (mainly constipation) seemed to favor transdermal opiates in the preference of patients with moderate-severe cancer pain [4-6]. Our previous meta-analysis of 12 Chinese literatures also found similar result [7].…”

“…But transdermal fentanyl is challenging the position because of its convenience, relative lower incidence of constipation and higher compliance of patients reported in clinical trials [42-44]. Clark et al and Tassinari et al in three meta-analyses reported two drugs were equally effective in improving the score of pain with less adverse effects for transdermal fentanyl [4-6]. …”

Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain

“…TD-O administration provides a slow and steady increase in opiate plasma levels, extended half-lives of several days, and a long latent period before full pharmacologic effects are achieved. Based on the current literature available on the use of TD-Fe and transdermal buprenorphine (TD-Bu) for cancer pain, no significant differences in efficacy were discerned between the transdermal preparations in comparison to other opioids 11,12,18–20…”

“…A meta-analysis conducted by the same group of researchers found that cancer and non-cancer patients experienced significantly less constipation and urinary retention, as well as preferring the use of TD-Fe over PO SR morphine 12. No significant differences were discerned between PO SR opiates and TD-Os (TD-Fe and TD-Bu) in overall AE, overall gastrointestinal AE, overall neurologic AE, nausea, somnolence, hypoventilation, withdrawal from trial, and changes in opioid therapy 12…”