Transmucosal, Oral Opioids Found to be Concordant for Breakthrough Pain in Opioid-Tolerant Patients with Chronic Pain

BALTIMORE, Md.—Determining an effective opioid dose for chronic pain in patients who become opioid tolerant can be challenging. In fact, effective dosing of a rapid-onset transmucosal opioid for breakthrough pain is not related to the around-the-clock dose, studies have shown. However, few data exist on the effective dose of the more traditional, short-acting oral opioids.

To determine an effective dose, investigators conducted a head-to-head study comparing fentanyl buccal tablets with oxycodone immediate-release (IR) for breakthrough pain. Based on the estimate that the relative potency of fentanyl buccal tablet 100 mcg is equivalent to oxycodone IR 7.5 mg, selected doses were fentanyl buccal tablet 200, 400, 600, and 800 mcg and oxycodone IR 15, 30, 45, and 60 mg.

Michael A. Ashburn, MD, MPH, of the Hospital of the University of Pennsylvania, Philadelphia, and colleagues evaluated each drug's efficacy during two randomized, crossover, double-blind, double-dummy periods. Mean age of the patients was 50.2 years and 58% were female; 92% were white.

Of 320 patients treated, 227 (71%) found a successful dose of fentanyl buccal tablet and 230 (72%) found a successful dose of oxycodone IR. Of those receiving fentanyl buccal tablets, 60 patients discontinued treatment during the titration period, as did 69 receiving oxycodone IR; 51% of all patients reported adverse events that were similar between treatments, as were reasons for study discontinuation.

No linear relationship between the successful dose of fentanyl buccal tablet or oxycodone IR and the around-the-clock opioid dose was observed. As measured by Kendall's tau statistic (tau = 0.62), used to measure the association between two measured quantities, the successful doses of fentanyl buccal and oxycodone IR exhibited a strong concordance (P<0.0001).

Both drugs had similar tolerability profiles. The most common adverse events were nausea (10%), headache (6%), and application site pain (4%). Adverse events led to 39 patients (12%) discontinuing the study, 36 during the titration phase and 3 during the double-blind treatment phase. Two serious adverse events (pneumonia) were reported for one patient that were not considered by the investigator to be related to the study drug.

Investigators reported that opioid-tolerant patients titrated both drugs to a dose that provided adequate analgesia—defined as the “successful” dose—with no unacceptable adverse events. Of those who entered the study taking oxycodone IR and identified a successful dose of each drug, 81% (78/96) titrated to a higher dose of oxycodone IR than they were using at study entry.

The titrated successful dose of oxycodone IR for breakthrough pain was not predicted by the around-the-clock opioid dose. The successful oxycodone IR dose was, however, concordant with a dose of fentanyl buccal tablet estimated to be equivalent, investigators told those attending the 29th Annual Scientific Meeting of the American Pain Society.