Purdue Pharma L.P. Receives FDA Approval for Butrans (Buprenorphine) Transdermal System CIII

STAMFORD, Conn., July 1 /PRNewswire/ -- Purdue Pharma L.P. announced today that the U.S. Food and Drug Administration (FDA) approved Butrans (buprenorphine) Transdermal System CIII for the management of moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid analgesic for an extended period of time. Butrans Transdermal System is an analgesic product that delivers continuous release of medication for seven days.

"Healthcare professionals now have an important new option for appropriate adult patients suffering from moderate to severe chronic pain when an opioid may be needed to manage their pain," said Lynn R. Webster, MD, FACPM, FASAM, Medical Director of the Lifetree Clinical Research and Pain Clinic in Salt Lake City, Utah.

The active ingredient in Butrans Transdermal System is buprenorphine, a partial agonist at mu opioid receptors and an antagonist at kappa opioid receptors. Butrans is a Schedule III product. Butrans can be abused in a manner similar to other opioid agonists, legal or illicit. Working with the FDA, Purdue has developed a Risk Evaluation and Mitigation Strategy (REMS) for Butrans that includes a Medication Guide, Elements to Assure Safe Use, such as healthcare providers training, and a timetable for submitting assessments of the REMS.

"We are very pleased with the FDA approval of Butrans and believe that it will be a valuable pain management option for healthcare professionals and patients," said John H. Stewart, president and CEO of Purdue Pharma L.P. "We are committed to improving the lives of patients in meaningful ways, including developing safe and effective therapies as well as offering educational tools and information that support their safe and proper use."

Butrans is indicated for the management of moderate to severe chronic pain in patients requiring a continuous, around-the-clock opioid analgesic for an extended period of time.

Butrans is contraindicated in patients who have significant respiratory depression, severe bronchial asthma, who have or are suspected of having paralytic ileus or known hypersensitivity to any of its components or the active ingredient, buprenorphine, as well as those who require opioid analgesia for a short period of time, who require the management of post-operative pain, including use after out-patient or day surgeries, the management of mild pain, and the management of intermittent pain (e.g., use on an as needed basis).

Three strengths of Butrans are available: 5, 10, and 20 mcg/hour; each single patch is intended to be worn for seven days. Do not exceed a dose of one 20 mcg/hour Butrans system due to the risk of QTc interval prolongation. Avoid exposing the Butrans application site and surrounding area to direct external heat sources. Temperature-dependent increases in buprenorphine release from the system may result in overdose and death.

Warnings and Precautions

• Use with extreme caution in patients at risk of respiratory depression.
• Use with caution in patients who are receiving other central nervous system (CNS) depressants.
• Additive CNS effects are expected when used with alcohol, benzodiazepines, other opioids, or illicit drugs.
• Avoid in patients with Long QT Syndrome, a family history of Long QT Syndrome, or those taking Class IA or Class III antiarrhythmic medications.
• Butrans may worsen increased intracranial pressure and obscure its signs, such as level of consciousness or pupillary signs.
• Use with caution in patients at increased risk of hypotension and in patients in circulatory shock.
• Ileus may occur; monitor for decreased bowel motility.
• Use with caution in patients with biliary tract disease, including acute pancreatitis.

Clinical Trial Experience

The efficacy of Butrans has been evaluated in four 12-week double-blind, controlled clinical trials in opioid-naïve and opioid-experienced patients with moderate to severe chronic low back pain or osteoarthritis using pain scores as the primary efficacy variable. Two studies in low back pain (described below) demonstrated efficacy while one study in low back pain failed to show efficacy and one study in osteoarthritis, that included an active comparator, failed to show efficacy for Butrans and the active comparator.

Evidence of efficacy has been provided through the study of more than 1200 patients in two pivotal analgesic trials. One trial enrolled patients who were opioid-naive while the other enrolled patients who were opioid-experienced. Each of these two adequate and well controlled trials enrolled patients suffering from moderate to severe chronic low back pain, included a 12-week double-blind phase and utilized pain scores as the primary efficacy variable. Butrans improved pain scores in opioid-naïve and opioid-experienced patients with moderate to severe chronic pain requiring continuous, around-the-clock treatment for an extended period of time.

Both of the pivotal clinical studies enrolled adult patients with moderate to severe chronic low back pain and included open-label titration periods followed by randomized, double-blind, 12-week study periods. One study was a placebo-controlled study that enrolled opioid naive patients who were suboptimally responsive to their non-opioid therapy (e.g., NSAIDs, acetaminophen). In this study, 53 percent of the patients who entered the open-label titration period were able to titrate to a tolerable and effective dose and were randomized into a 12-week, double-blind treatment period. Twenty three percent of patients discontinued due to an adverse event and 14 percent discontinued due to lack of a therapeutic effect from the open-label titration period. During the double-blind treatment, in the Butrans 10 or 20 mcg/hour group, 9 percent discontinued early due to lack of efficacy and 16 percent due to adverse events; in the placebo group, 13 percent discontinued early due to lack of efficacy and 7 percent due to adverse events.

The second study used a low dose Butrans control group (Butrans 5 mcg/hour) and enrolled patients who had been previously treated with a variety of opioids in conjunction with or without non-opioid therapies. In this study, 57 percent of the patients who entered the open-label titration period were able to titrate to and tolerate the adverse effects of Butrans 20 mcg/hour and were randomized into a 12-week double-blind treatment phase. Twelve percent of patients discontinued due to an adverse event and 21 percent discontinued due to lack of a therapeutic effect during the open-label titration period. During the double-blind treatment, in the Butrans 20 mcg/hour group, 11 percent discontinued early due to lack of efficacy and 13 percent due to adverse events; in the Butrans 5 mcg/hour group, 24 percent discontinued early due to lack of efficacy and 6 percent due to adverse events.

Adverse Event Information

The most common adverse events (greater than or equal to 5%) reported by patients treated with Butrans in the clinical trials were nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash. The most frequently occurring application site skin reactions were application site pruritus, erythema, rash and irritation. In rare cases, severe application site skin reactions with signs of marked inflammation including "burn," "discharge," and "vesicles" have occurred.

The professional product labeling for Butrans contains the following Boxed Warning:

The Full Prescribing Information for Butrans is available at www.purduepharma.com/PI/prescription/ButransPI.pdf. Additional information, including a Medication Guide, will be available at www.Butrans.com.

About Purdue Pharma L.P.

Purdue Pharma L.P. and its associated U.S. companies are privately-held pharmaceutical companies known for pioneering research on persistent pain. Headquartered in Stamford, CT, Purdue Pharma is engaged in the research, development, production, and distribution of both prescription and over-the-counter medicines and hospital products. Additional information about Purdue can be found at www.purduepharma.com.

SOURCE Purdue Pharma, LP