Portenoy, R.K., Raffaeli, W., Torres, L.M., Sitte, T., Deka, A.C., Herrera, I.G., . . . Fentanyl Nasal Spray Study 045 Investigators Group. (2010). Long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray for breakthrough cancer pain in opioid-tolerant patients. Journal of Opioid Management, 6(5), 319–328.

To evaluate the safety and tolerance of fentanyl-pectin nasal spray for cancer-related breakthrough pain

Patients completed an open dose-titration phase for dose determination and then entered a 16-week open label treatment phase. Patients were instructed to administer the effective dose from titration for a maximum of four episodes of breakthrough pain per day. If pain relief was inadequate after 30 minutes, patients could take the prestudy rescue medication. Investigators contacted patients at least weekly to review appropriate use of study medication, to discuss the need for dose adjustment and nasal symptoms, and to review use of rescue medication. Patients also rated nasal symptoms by using a 10-point questionnaire. A physician performed graded nasal assessments at baseline, week 8, and week 16.

• Authors reported that 110 patients completed the entire 16 weeks of the study.
• Authors reported 42,227 breakthrough pain episodes in 403 patients included in the analysis.
• Mean patient age was 53.8 years. The age range was 21–84 years.
• Of all patients, the percentage of females was 46.9% and the percentage of males was 53.1%.
• Authors did not report diagnosis information.
• Of all patients, 59.8 % were on morphine; 31.5%, on fentanyl; and 14.4%, on oxycodone. These drugs were used for the treatment of  background pain.

• Multisite
• Outpatient
• Multiple countries

Open label trial

• Nasal-symptom questionnaire, offering a four-point assesment scale for each of the following: stuffy/blocked nose, runny nose, itching/sneezing, crusting/dryness, burning/discomfort, nose bleeding, cough, postnasal drip, sore throat, and taste disturbance
• Measures of the neeed for rescue medication other than the study drug

• Authors reported that 110 patients completed the full 16-week extension trial.
• Of all patients, 24.6% had treatment-related adverse events. The most common adverse events were dizziness, vomiting, constipation, and somnolence, which occurred in 3.5%–5.2% of patients.
• Doses of fentanyl spray were 100–800 micrograms. Authors did not relate overall dose to adverse events.
• For most patients, the results of nasal examination at the end of the study were normal. Authors observed no consistent pattern in patient-reported nasal symptoms.
• Of the 42,227 breakthrough episodes, 94% did not require additional rescue medication to be resolved.

Fentanyl-pectin nasal spray for cancer-related breakthrough pain appears to be well tolerated over a use period of four months.

The study has a risk of bias due to no appropriate control group.

This study showed that, over a four-month period, patients tolerated the fentanyl-pectin nasal spray well. This study suggests that long-term use is not associated with significant adverse nasal events. Fentanyl-pectin nasal spray used as specified, for the treatment of breakthrough cancer-related pain, was effective for the majority of patients. Fentanyl-pectin nasal spray is a rapidly acting treatment for breakthrough pain that can be particularly helpful to patients who have difficulty with oral intake.