Mercadante, S., Adile, C., Cuomo, A., Aielli, F., Cortegiani, A., Casuccio, A., & Porzio, G. (2015). Fentanyl buccal tablet vs. oral morphine in doses proportional to the basal opioid regimen for the management of breakthrough cancer pain: A randomized, crossover, comparison study. Journal of Pain and Symptom Management, 50, 579–586. 

To compare the safety and effectiveness of fentanyl buccal tablets and oral morphine for breakthrough cancer-related pain

After ensuring stable background pain control with severity less than or equal to four on a 10-point scale, patients were instructed to call for breakthrough medication when pain became severe or was distinguishable from chronic background pain. Patients randomly received either fentanyl buccal tablets or oral morphine in does proportional to doses used for ongoing analgesia. After receiving one medication per breakthrough, patients were crossed over to receive the alternative medication. Patients received each drug for two breakthrough episodes. Nurses recorded pain intensity just before drug administration, at 15 minutes, and at 20 minutes. The intensity of adverse effects was recorded.

• N = 68 (263 breakthrough episodes)
• MEAN AGE = 62.1 years (SD = 12.3 years)
• MALES: 60.5%, FEMALES: 39.5%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types with lung, gastrointestinal, and urogenital the most frequent
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had controlled background pain and one to three episodes of breakthrough pain per day.

• SITE: Multi-site  
• SETTING TYPE: Inpatient  
• LOCATION: Italy

• APPLICATIONS: Palliative care

Randomized, single-group, crossover study

• 10-point Numeric Rating Scale (NRS) for pain intensity
• Three-point scale for adverse effect severity

Both medications resulted in significant pain reductions (p = 0.0005). Pain intensity at 15 and 30 minutes was significantly lower with fentanyl buccal tablets (p < 0.0005) compared to oral morphine. There were no differences between groups in the severity of adverse effects. The most common adverse effect was nausea and vomiting, and these events were not severe. Of the patients who received both treatments, twice as many patients preferred the fentanyl tablets.

The analgesic effect for breakthrough pain was greater with the use of fentanyl buccal tablets compared to oral morphine, and the tablets were well-tolerated.

• Small sample (< 100)
• Risk of bias (no blinding)

Fentanyl buccal tablets were shown to have greater analgesic effects for breakthrough pain than oral morphine when both medications were given at doses proportional to background analgesia. Some studies suggested that transmucosal opioids need to be titrated, which can delay efficacy, but this study showed that proportional dosage administration was effective. Pain can be one of the most debilitating and problematic symptoms to manage, and it is important that patients have rapid and effective interventions for breakthrough pain. Nurses can advocate for the use of the most effective medications for pain management and the approaches that are preferred by patients. Significant differences in efficacy may justify the use of more expensive drugs.