Portenoy, R.K., Burton, A.W., Gabrail, N., Taylor, D., & Fentanyl Pectin Nasal Spray 043 Study Group. (2010). A multicenter, placebo-controlled, double-blind, multiple-crossover study of Fentanyl Pectin Nasal Spray (FPNS) in the treatment of breakthrough cancer pain. Pain, 151(3), 617–624.

To demonstrate the safety and efficacy of fentanyl-pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain

Consenting patients entered an open label-titration phase for determination of effective dose of FPNS. Effective dose was defined as a dose that achieved successful treatment of two breakthrough episodes. In the titration phase, if pain relief was unacceptable at 30 minutes, the patient was able to take his or her previous rescue medication. Doses were sequentially increased up to 800 mcg. Individuals who achieved an effective dose were eligible to continue in the double-blind stage. Patients received randomly assigned separate bottles, identified by number. Patients were instructed to use the bottles in the order designated. Each breakthrough episode was treated with a single dose. Pain that continued to require treatment after 30 minutes was treated with the patient’s usual rescue medication. Electronic diaries were used for data collection. Patients recorded pain intensity and pain relief at 5, 10, 15, 30, 45, and 60 minutes. Adverse events were recorded throughout the study, and visual nasal assessments were performed by the study physician at baseline and at the end of treatment. Maximum study duration was eight weeks.

• Seventy-three patients were in the intent-to-treat analysis.
• Mean patient age was 53.8 years (SD = 1 year).
• Of all patients, 46.9% were female and 53.1% were male.
• The study included multiple tumor types. The most common were lung, breast, reticuloendothelial, and bowel.
• All patients were receiving, on a regular basis, opioids for the treatment of pain. The most common opioids for the treatment of background pain were morphine, fentanyl, oxycodone, and methadone. Of all patients, 26% were taking multiple opioids.

Multisite (26 in the United States and 2 in other countries)

Randomized double-blind placebo-controlled crossover study

• 11-point scale, to measure pain intensity
• Five-point scale, to measure overall satisfaction
• Five-point scale, to measure ease of use
• Five-point scale, to rate nasal symptoms

• Thirteen patients (15.7% of those randomized) withdrew from the study because of lack of efficacy or adverse effects.
• At 5 minutes and sustained over all other time points, the mean pain-intensity score for FPNS-treated episodes was significantly lower  (p = 0.03) than that for placebo-treated episodes. At 5 minutes, 33% of patients reporting on FPNS-treated episodes noted a drop of one point or more. At 10 minutes, 61% of patients reporting on FPNS-treated episodes noted a drop of one point or more; at 30 minutes, 73% noted a drop of one point or more.  
• Of all FPNS-treated episodes, 90.6% did not require additional rescue medication. Of all placebo-treated episodes, 80% did not require additional rescue medication.
• Authors noted significantly lower pain intensity (p < 0.0001) with FPNS at 60 minutes.
• Clinical assessment of each patient's nose revealed no changes.
• In regard to adverse events, authors noted no significant differences between treatments. 
• In an open label extension after study conclusion, 87% of patients chose to continue use of FPNS.

FPNC is effective and well tolerated for treatment of breakthrough cancer pain.

• The study had a small sample size, with fewer than 100 patients.
• Authors noted a high response to placebo.
• The study period was relatively short. Whether nasal complications might occur with long-term treatment with FPNS is unclear.

FPNS is an effective approach to the management of the breakthrough pain of patients with cancer who are taking opiods for relief of background pain. FPNS can be a useful alternative in situations where clinicians want to reduce the number of oral medications. Studies of the use of nasal sprays have been relatively brief, so nurses must remain aware of the need to assess the patient’s nares and related symptoms.