Patients taking morphine or oxycodone for pain can be safely switched to buprenorphine buccal film without the need for tapering and without causing significant withdrawal or undertreatment of their pain, a new randomized trial suggests.
Buprenorphine HCl buccal film is a new transmucosal form of buprenorphine delivered using a small patch placed on the mucosa of the inner cheek. The delivery system technology is called BEMA (BioErodible MucoAdhesive, Biodelivery Sciences).
Because an opioid rotation is potentially dangerous, prescribers are always searching for safer analgesics for patients with chronic pain, said lead study author Lynn Webster, MD, vice president of Scientific Affairs at PRA Health Sciences, Salt Lake City, Utah. “This may be an effective alternative to other opioids for many patients.”
The research was presented here during PAINWeek 2015.
Buprenorphine has been used clinically for more than 40 years. Depending on the dose, it has several uses, including treating opioid addiction, controlling moderate acute pain, and managing moderate chronic pain. A transdermal buprenorphine product (Butrans, Purdue Pharma) is already approved by the US Food and Drug Administration for pain severe enough to require daily, round-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Buprenorphine buccal film is a new delivery system for buprenorphine. With this type of delivery, the drug can be used for chronic as well as acute pain in an ambulatory setting. Because it’s a partial agonist, it isn’t as potent as other opioids, Dr Webster said.
This could be an advantage, he noted. Because buprenorphine is only a partial agonist, it doesn’t produce the same amount of respiratory depression as other opioids that are pure mu agonists.
“This might make it a safer opioid, although it may not be as efficacious for severe pain,” said Dr Webster.
As it binds more tightly to the opioid receptor, buprenorphine has the potential to displace a pure mu agonist opioid such as morphine, oxycodone, hydrocodone, fentanyl, or even heroin, he said. On the other hand, if it displaces an opioid in someone who has become physically dependent, it could induce withdrawal.
The current analysis included adult opioid-dependent patients who had been receiving long-term opioid therapy for more than 28 days. They were separated into two groups based on their daily opioid dose: Group 1 (n = 33) received 80 to 160 mg morphine equivalents (ME) of morphine or oxycodone, and group 2 (n = 6) received 161 to 240 mg ME of morphine or oxycodone.
Patients were randomly assigned to receive BEMA or 50% of their normal opioid dose.
Researchers assessed withdrawal using the Clinical Opioid Withdrawal Scale (COWS), level of pain relief using the numeric rating scale (NRS), and safety with the number of adverse events during the 24 hours after dosing. Patients returned to the clinic in 7 to 14 days to undergo the crossover treatment and a second monitoring period.
Of the 35 patients, one patient receiving buccal buprenorphine and two receiving the full agonist experienced significant withdrawal. No patient had a COWS total score of 13 or greater up to 6 hours after dosing, indicating no difference between groups.
There were also no between-treatment differences in changes from baseline in NRS pain scores during the 24-hour study periods for group 1 (80 to 160 mg ME). The sample size for group 2 (161 to 220 mg ME) was too small to analyze.
In group 1, 20 patients (60.6%) had at least one treatment emergent adverse event. In group 2, one patient (16.7%) had such an event. The most common adverse events were nausea and vomiting, which are usual adverse events with opioids.
Because the study showed only a successful switch from oxycodone or morphine to BEMA within a specified dose range, a switch from other opioids or at other doses will need to be evaluated, said Dr Webster.
Clinicians themselves would have to determine which patients should be switched to this therapy. “But in general, when a pure mu agonist appears to be ineffective or the dose is creating more risk than harm, buprenorphine could be an option,” said Dr Webster.
But because buprenorphine is an opioid, there’s still a potential for abuse. “Patients who may divert the drug or who clearly cannot be compliant are not candidates,” said Dr Webster.
Asked to comment, Scott Novak, PhD, senior developmental epidemiologist, RTI International, Research Triangle Park, North Carolina, whose research interests include prescription drug abuse, said this therapy approach could be “revolutionary” in terms of weaning patients off opioids while possibly avoiding withdrawal or long-term addiction.
“What happens is that patients are put on chronic opioid therapy for an extended period of time — many, many months to many, many years — and their body builds up a tolerance. The moment the doctor starts tapering the patient down, the patient starts to feel very uncomfortable.”
Although not life-threatening, withdrawal symptoms can be extremely uncomfortable and can include sleep and cognitive disturbances. Such symptoms are often the reason pain patients continue to take opioids.
“The patient continues using the opioid not because he likes the high; he needs to keep using to feel normal,” said Dr Novak.
Patients in his research groups often tell him that their first exposure to opioids was from a legitimate prescription. They then lie to their doctor about having stopped the opioid and the doctor never drug tests them.
“There is a huge role for this in terms of population public health,” said Dr Novak of the new drug delivery technology. “This is one potentially very important tool that could be used in the fight against addiction.”
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