Uberall, M.A., & Muller-Schwefe, G.H. (2011). Sublingual fentanyl orally disintegrating tablet in daily practice: Efficacy, safety and tolerability in patients with breakthrough cancer pain. Current Medical Research and Opinion, 27(7), 1385–1394.

To evaluate the efficacy of sublingual fentanyl orally disintegrating tablets (ODT) on breakthrough cancer pain; to assess the safety of sublingual fentanyl ODT and its impact on quality of life

Investigators followed patients through a 28-day observation period. Patients self-administered sublingual fentanyl ODTs on an as-needed basis for breakthrough pain episodes. The initial dose was determined by the clinician on the basis of previous treatment; the clinician titrated the dose as necessary. Patients used a questionnaire to record maximum breakthrough pain intensity, time to first effect, and time to maximum effect. Patients who had previously used breakthrough pain medication rated the effectiveness of the sublingual fentanyl ODTs in regard to speed, strength, and duration of action. During clinic visits on days 3, 7, 14, and 28, clinicians observed and recorded data about adverse events. Clinicians recorded measures of pain intensity at baseline and after 3, 7, and 14 days. Clinicians obtained anxiety and quality-of-life measures at baseline and at the end of the study.

• The sample was composed of 181 patients, and the study comprised 3,163 episodes of breakthrough pain.
• Mean patient age was 64.4 years. Age range was 35–89 years.
• Of all participants, 47.7% were female and 52.3% were male.
• Authors did not provide specific cancer-site information.
• At baseline, mean daily opioid use for background pain was 116.1 mg morphine equivalent. The range of daily opioid use for background pain was 60–240 mg.
• Mean pain intensity of background pain at baseline was 4.8. Mean number of breakthrough episodes was 2.7/day.
• The medications most commonly used for breakthrough pain were oral immediate-release liquid morphine, which 66% of patients used; oral transmucosal fentanyl citrate, which 13.2% of patients used; and oral immediate-release liquid hydromorphone, which 9.4% of patients used.

• Multisite
• Outpatient
• Germany

Prospective trial

• Numeric scale (0–10), to measure pain intensity
• Questionnaire, to measure breakthrough pain intensity maximum, time to first effect, and time to maximum effect
• Seven-point scale, to measure effect of study drug compared to that of previous medication in regard to speed of action, strength of action, duration of action, tolerability, and ease of handling
• Hospital Anxiety and Depression Scale (HADS)
• Modified Pain Disability Index (PDI)

With the study drug, breakthrough pain decreased signficantly (p < 0.00001), with mean pain intensity changing from 7.8 at baseline to 2.6. Patients reported that time to first effect was 10 minutes or less in 82.8% of episodes, less than 2 minutes in 19.4% episodes, and 2–5 minutes in 48.3% of episodes. Time to maximum effect was 30 minutes or less in 63.2% of episodes. In 83 patients who had previously used other medications for breakthrough pain, 87.7% said the study drug was better in speed of action; 85.7%, strength of action; 83.9%, duration of action; 88.6%, tolerability; and 87.3%, ease of handling. PDI scores decreased during the study (p < 0.0001). Prevalence of abnormal HADS scores declined. In regard to anxiety, 54.5% had abnormal scores at baseline; 1.6% had abnormal scores at the end of the study (p < 0.0001). In regard to depression, 70.3% had abnormal scores at baseline; 15.6% had abnormal scores at the end of the study (p < 0.0001). Mean dose per episode during the study was 400 mcg; dose range was 100–1600 mcg. Of all patients, 5.5% experienced at least one drug-related adverse event. The most common adverse events were nausea, somnolence, dizziness, and vomiting. At the end of the study, 84% of patients chose to continue taking sublingual fentanyl ODT.

Sublingual fentanyl ODT was effective in the treatment of breakthrough cancer pain. The drug had an acceptable safety profile and was associated with improvement in symptoms of anxiety and depression and improvement in pain-related disability scores.

• The study had a risk of bias due to no appropriate control group.
• Patients' recollection of experience with previous medications was the only basis of comparison regarding efficacy.
• Authors provide no information about missing data or patients' adherence to instructions about completing measurement assessments.
• Authors provide minimal demographic information about the sample.

Sublingual fentanyl ODT was a very effective and fast-acting treatment for breakthrough cancer pain. This drug appears to be an important addition to options for the management of breakthrough pain.