BUTRANS™ (buprenorphine) TRANSDERMAL SYSTEM CIII NOW AVAILABLE
Stamford, CT, January 20, 2011 – Butrans™ (buprenorphine) Transdermal System CIII from Purdue Pharma L.P. is now available by prescription and 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 Transdermal System is the first opioid analgesic that delivers continuous release of buprenorphine for seven days.
“Because individuals experience moderate to severe chronic pain and respond to treatment differently, additional therapeutic options can help us address the needs of our patients,” said Joseph V. Pergolizzi, M.D., Adjunct Professor of Georgetown University, and President and Board member of the Association for Chronic Pain Patients. “Butrans may provide healthcare professionals with a new tool for appropriate adult patients with moderate to severe chronic pain who meet the indication of the product.”
The active ingredient in the Butrans Transdermal System is buprenorphine. Butrans is a Schedule III product and 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. This information is available at www.purduesrems.com.
Three strengths of Butrans are available by prescription in retail pharmacies nationwide: 5 mcg/hour (NDC code 59011-750-04); 10 mcg/hour (NDC code 59011-751-04); and 20 mcg/hour (NDC code 59011-752-04). The maximum dose of Butrans is 20 mcg/hour.
“The commercial launch of Butrans represents an important milestone in our long-term commitment to develop new products that fulfill unmet therapeutic needs of moderate to severe chronic pain patients,” said John H. Stewart, president and CEO of Purdue Pharma L.P.
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).
The professional product labeling for Butrans contains the following Boxed Warning:
WARNING: IMPORTANCE OF PROPER PATIENT SELECTION, POTENTIAL FOR ABUSE, AND LIMITATIONS OF USE
Proper Patient Selection
Butrans is a transdermal formulation of buprenorphine 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.
Potential for Abuse
Butrans contains buprenorphine which is a mu opioid partial agonist and a Schedule III controlled substance. Butrans can be abused in a manner similar to other opioid agonists, legal or illicit. Consider the abuse potential when prescribing or dispensing Butrans in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
Persons at increased risk for opioid abuse include those with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Assess patients for their clinical risks for opioid abuse or addiction prior to being prescribed opioids. Routinely monitor all patients receiving opioids for signs of misuse, abuse and addiction.
Limitations of Use
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.
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.
WARNINGS AND PRECAUTIONS
- Respiratory Depression: Respiratory depression is the chief hazard with Butrans. Use with extreme caution in patients at risk of respiratory depression.
- CNS Depression: Butrans may cause somnolence, dizziness, alterations in judgment and alterations in levels of consciousness, including coma. 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.
- QTc Prolongation: Avoid in patients with Long QT Syndrome, family history of Long QT Syndrome, or those taking Class IA or Class III antiarrhythmic medications.
- Head Injury: Butrans may worsen increased intracranial pressure and obscure its signs, such as level of consciousness or pupillary signs.
- Hypotensive effects: Butrans may cause severe hypotension. Use with caution in patients at increased risk of hypotension and in patients in circulatory shock.
- Application Site Skin Reactions: In rare cases, severe application site skin reactions with signs of marked inflammation including “burn,” “discharge,” and “vesicles” have occurred.
- Anaphylactic/Allergic Reactions: Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in the post-marketing experience.
- Use in Pancreatic/Biliary Tract Disease and Other Gastrointestinal Conditions: Use with caution in patients with biliary tract disease, including acute pancreatitis. Ileus may occur. Monitor for decreased bowel motility.
ADVERSE EVENT INFORMATION
The most common adverse events (≥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.
CLINICAL TRIAL EXPERIENCES
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 1,200 patients in two pivotal analgesic trials. One trial enrolled patients who were opioid-naïve 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.
The Full Prescribing Information for Butrans, including the Medication Guide and Boxed Warning is available at www.purduepharma.com/PI/prescription/ButransPI.pdf and 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.