Transdermal Fentanyl: An Updated Review of its Pharmacological Properties and Therapeutic Efficacy in Chronic Cancer Pain Control

Muijsers, R.B.R.; Wagstaff, A.J.
December 2001
Drugs;Dec2001, Vol. 61 Issue 15, p2289
Academic Journal
Fentanyl is a synthetic opioid agonist which interacts primarily with the µ-opioid receptor. The low molecular weight, high potency and lipid solubility of fentanyl make it suitable for delivery by the transdermal therapeutic system. These patches are designed to deliver fentanyl at a constant rate (25, 50, 75 and 100 µg/h), and require replacement every 3 days. Data from randomised, nonblind trials suggest that transdermal fentanyl is as effective as sustained-release oral morphine in the treatment of chronic cancer pain, as reported by patients using visual and numerical analogue scales as well as verbal description scales. No obvious differences in health-related quality of life were found in patients with chronic cancer pain when comparing transdermal fentanyl with sustained-release oral morphine. Nevertheless, significantly more patients expressed a preference for transdermal fentanyl than for sustained-release oral morphine after a randomised, nonblind, crossover trial. Because of the formation of a fentanyl depot in the skin tissue, serum fentanyl concentrations increase gradually following initial application, generally levelling off between 12 and 24 hours. Thereafter, they remain relatively constant, with some fluctuation, for the remainder of the 72-hour application period. Once achieved, steady-state plasma fentanyl concentrations can be maintained for as long as the patches are renewed. The most frequently observed adverse events during transdermal fentanyl administration (as with other opioid agonists) included vomiting, nausea and constipation. Data from a nonblind, randomised trials suggest that constipation occurs less frequently in patients receiving transdermal fentanyl than in those given sustained-release oral morphine. The most serious adverse event reported in US premarketing trials was hypoventilation, which occurred with an incidence of approximately 2%. Adverse reactions related to skin and appendages (i.e. rash and application site reactions - erythema, papules, itching and oedema) were reported in 153 patients with cancer at a frequency between 1 and 3%. Conclusion: Transdermal fentanyl is a useful opioid-agonist for the treatment of moderate to severe chronic cancer pain. The advantages of transdermal fentanyl include ease of administration and the 3-day application interval. These factors coupled with a lower incidence of constipation are likely to contribute to the reported patient preference of transdermal fentanyl over sustained-release oral morphine.


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