Rauck, R.L., Tark, M., Reyes, E., Hayes, T.G., Bartkowiak, A.J., Hassman, D., . . . Howell, J. (2009). Efficacy and long-term tolerability of sublingual fentanyl orally disintegrating tablet in the treatment of breakthrough cancer pain. Current Medical Research and Opinion, 25, 2877–2885.doi: 10.1185/03007990903368310
To evaluate the effect of sublingual fentanyl on breakthrough cancer pain in opioid-tolerant patients; to assess how well patients tolerate sublingual fentanyl
The study included an open-label titration phase, a two-week double-blind efficacy phase, and a long-term open-label safety phase of up to 12 months duration. Sublingual orally disintegrating tablet (ODT) fentanyl was given at 100 mcg and titrated in the open-label phase to a maximum dose of 800 mcg until patients identified a single effective and tolerable dose. In the double-blind phase, patients received seven doses of the study drug and three doses of placebo. The study drug and placebo were identical in appearance. Patients took doses in a randomly assigned sequence. Rescue medication could be administered if needed after two hours. Patients were followed on a daily basis by telephone to monitor use of the study and rescue medications and the incidence of adverse events during the titration phase. Thereafter, investigators monitored patients in person on a monthly basis and at two weeks after monthly by-telephone evaluations. Patients maintained an electronic daily diary. Pain intensity and pain relief were recorded immediately prior to treatment and at 10, 15, 30, and 60 minutes after use.
Randomized placebo-controlled phase III trial
Overall, patients received the study drug for an average of 51 days. Median dose of ODT fentanyl was 600 mcg. A median of three doses were taken per day. The most common treatment-related complications were nausea (12.2%), vomiting (5.3%), and somnolence (4.6%). One patient developed stomatitis, which may have been related to the study drug. Sublingual ODT fentanyl was significantly more effective (p < 0.006) than placebo at all time points and was most effective at 60 minutes (p = 0.0004). Pain relief was significantly better with ODT fentanyl than with placebo (p = 0.0007) at 15 minutes after use and at 30 and 60 minutes.
Sublingual ODT fentanyl was effective in the management of breakthrough pain, and patients tolerated the medication well.
In this study ODT fentanyl was effective in treating breakthrough pain; therefore, ODT fentanyl may be an appropriate means to manage this problem. The study reported one case of stomatitis, which may have been related to this drug. Nurses should be aware of the potential of stomatitis occurring with a patient's use of ODT fentanyl. The follow-up period in the present study was relatively short. Longer use of ODT fentanyl may pose greater risk of stomatitis.