NATIONAL HARBOR, Md. — A transmucosal formulation of buprenorphine may offer a new treatment option for patients with severe pain who require daily, around-the-clock, long-term opioid treatment.
Currently, patients taking around-the-clock (ATC) full mu-opioid agonists, must be tapered to a 30 mg morphine sulfate equivalent (MSE) dose before being switched to buprenorphine to avoid withdrawal smptoms. But buprenorphine HCI buccal film may eliminate the need for an opioid taper, data presented on a poster at the American Academy of Pain Management 2015 meeting indicate.
Administration of buprenorphine HCI buccal film (300 to 450 µg) 8 to 12 hours after the last full mu-opioid dose (80-220 mg MSE) was not associated with a higher incidence of opioid withdrawal or adverse events compared with 50% ATC full mu-opioid agonist dosage.
The randomized, double-blind, two-period crossover study conducted by Lynn Webster, MD, of PRA Health Sciences in Salt Lake City, Utah, and colleagues, involved 39 patients aged 18 to 60 years with a 6 month or longer history of chronic pain who were receiving ATC full mu-opioid agonist therapy with either morphine sulfate or oxycodone HCI.
All patients were taking an opioid dosage ranging from 80-220 MSE per day for at least 28 days and were confirmed to be opioid-dependent by naloxone challenge. Patients were then stratified into two groups based on ATC MSE dosage — group one consisted of patients who required between 80-160 mg MSE per day (n=33); group two consisted of those who required 161-220 mg MSE per day (n=6).
After an initial visit to assess eligibility and perform the naloxone challenge, patients were randomly assigned to one of two treatment sequences — AB or BA. Treatment A consisted of two doses of buprenorphine HCI buccal film 300 to 450 µg; treatment B consisted of two doses of full-mu agonist ATC opioid at 50% of original MSE dose.
Patients were then administered buccal film containing either buprenorphine or placebo plus a capsule containing either morphine, oxycodone, or placebo according to their treatment sequence assignment. They were monitored in the clinic for 12 hours for signs and symptoms of opioid withdrawal, administered the second treatment, and monitored for another 12-hour period. Study participants returned 7 to 14 days later to repeat the process with the alternate drug.
Overall 31 patients in group one and 4 patients in group two completed both study periods and were evaluable for opioid withdrawal status. One patient on buccal buprenoprhine experienced significant withdrawal and two patients on the full agonist.
No patient had a COWS total score >13 in the 6 hours post-dose, indicating no difference between buprenorphine and ATC opioid in the risk of precipitated withdrawal, the researchers reported.
Mean maximum COWS scores were similar between patients taking the buccal buprenorphine and full mu-opioid agonists (mean 4.6 and 5.3, respectively), and mean COWS total score changes from baseline were similar for both treatments. There were no differences in pain scores among patients in the 80 to 160 mg MSE dose range, the researchers reported.
The most frequent adverse events with buprenorphine were headache (18.8%), vomiting (12.5%), nausea, diarrhea, and drug withdrawal syndrome (9.4% each). With full opioid agonists, the most frequent adverse events were headache (15.6%), drug withdrawal syndrome (12.5%), and nausea (6.3%).
“The results demonstrate that in this study, chronic pain patients treated with around-the-clock full mu-opioid agonist therapy in the dose range of 80-220 mg MSE were successfully switched to buprenorphine HCI buccal film without the need for an opioid taper, at approximately 50% of the full mu-opioid agonist dose without an increased risk for experiencing opioid withdrawal,” the researchers wrote.
Disclosures: Todd Kirby, PhD, is an employee of Endo Pharmaceuticals Inc., which provided funding for this research.
- Webster L, Gruener D, Kirby T et al. Poster #26. “Evaluation of the Tolerability of Switching Patients on Chronic Full Opioid Agonist Therapy to Buprenoprhine HCI Buccal Film.” Presented at: AAPM 2015. Sept. 17-20; National Harbor, Maryland.