Transdermal fentanyl: clinical development in the United States.

The first clinical experience in the United States of the transdermal therapeutic system (TTS) for delivery of fentanyl in cancer pain was a small study of five patients. Pain relief was established with intravenous (i.v.) fentanyl. A transdermal system was selected to deliver the same hourly dose while the i.v. infusion was tapered over 6 h. The transdermal system was changed every 24 h for a total duration of 3-156 days. A larger multicentre outpatient trial was conducted in 39 patients for a median of 84 days (range 5-365). The TTS fentanyl dose was established from a conversion table based on the dose of oral immediate-release morphine required to control pain. The TTS fentanyl patches were changed every 72 h. Immediate-release morphine was used on an as required basis for incident pain. The initial study demonstrated that steady-state plasma levels were linearly related to the TTS fentanyl dose. The multicentre trial further demonstrated that patients could be converted from oral morphine to an equianalgesic dose of TTS fentanyl and that pain relief could be maintained for a lengthy period of time on an outpatient basis. The systems were used throughout a variety of concomitant complications of the cancer process. This experience demonstrated the safety and clinical effectiveness of TTS fentanyl in the treatment of chronic cancer pain. TTS fentanyl has been used widely in the USA since it was approved for marketing in 1990.