Fentanyl Buccal Tablets Safe, Well Tolerated in Cancer Patients

Fentanyl Buccal Tablets Safe, Well Tolerated in Cancer Patients

Stephanie Doyle

February 18, 2008 (Kissimmee, Florida) — The largest and longest study of its kind to date suggests that fentanyl buccal tablets (Fentora, Cephalon) generally are safe and well tolerated in the long-term treatment of breakthrough pain in opioid-tolerant cancer patients.

The findings were presented here at the AmericanAcademy of Pain Medicine 24th Annual Meeting, on the heels of an advisory from the US Food and Drug Administration (FDA) alerting health professionals and consumers to reports of life-threatening and sometimes fatal events in patients receiving fentanyl buccal tablets.

The events were associated with improper patient selection (for example, opioid-intolerant patients or patients who did not have cancer), improper dosing, and/or improper product substitution for nonequianalgesic fentanyl-containing products. The warning, issued in September 2007, strongly advised physicians and other healthcare professionals to follow product labeling when prescribing fentanyl tablets to minimize the risk for respiratory depression.

Fentanyl buccal tablets are designed to manage the breakthrough pain associated with chronic pain. The medication is 1 of only a few available to cancer patients for breakthrough pain that has a rapid onset of action, providing relief for pain that comes on suddenly, explained Sharon Weinstein, MD, director of pain management and palliative care at Huntsman Cancer Institute, in Salt Lake City, Utah, and lead investigator of the study.

Dr. Weinstein commented on the FDA advisory to Medscape Neurology & Neurosurgery: "Like all opioids, there are some guidelines that should be followed." Of deaths related to fentanyl buccal tablets, see said, "Those are of course tragic and for the most part avoidable. When the proper medical oversight is used, this drug can be used safely."

Breakthrough Pain

In the multicenter study presented here, which was funded by Cephalon, adults taking opioids around the clock for 1 to 4 episodes of breakthrough pain daily were maintained at the successful dose of fentanyl buccal tablets they attained in 1 of 2 previous clinical studies (120 rollover patients) or titrated to a successful new dose of between 100µg and 800µg (110 treatment-naive patients; 2 retitrated rollover patients).

Monthly assessments included the number of daily episodes of breakthrough pain, the daily dosage of fentanyl buccal tablets, and the number and type of adverse events.

As a result, 197 patients entered the dose-maintenance phase, including 79 patients who achieved a successful dose of fentanyl buccal tablets during titration.

During the maintenance phase, the median duration of exposure to fentanyl buccal tablets was 122 days (range, 1 – 698; 36 patients [18%] had exposure ≥12 months). The mean (± SE) dose per breakthrough-pain episode was 554.8 ± 18.6µg. The final dose was the same as the initial successful dose for 136 patients (69%), including patients with dose changes during the study who shifted back to the initial dose.

Three patients discontinued therapy because of a lack of efficacy, and 71 discontinued because of adverse events typical of opioid use and consistent with those observed in short-term studies: during titration, nausea was reported in 27 patients, vomiting in 4, and dizziness in 29. During maintenance, nausea was reported in 62 patients, vomiting in 47, and dizziness in 20.

Serious adverse events included disease progression in 62 patients and pneumonia in 16; all serious adverse events were deemed by investigators to be unrelated to the study medication, except drug-withdrawal syndrome in 1 patient.

"Yes, it works, and yes, it's safe," said Todd Sitzman, MD, president of the AmericanAcademy of Pain Medicine, who was not involved in the study. "Some of the unfortunate consequences that were associated with this medicine earlier were in patients without tolerance to opioid analgesics."

Funding was provided by Cephalon Inc. Dr. Weinstein has disclosed no relevant financial relationships.

AmericanAcademy of Pain Medicine (AAPM) 24th Annual Meeting: Abstract 119.