Purdue Pharma L.P. Receives FDA Approval for 7.5 mcg/hour Dosage Strength of Butrans® (Buprenorphine) Transdermal System CIII

STAMFORD, Conn., July 16, 2014 /PRNewswire/ -- Purdue Pharma L.P. announced that the U.S. Food & Drug Administration (FDA) approved a new 7.5 mcg/hour dosage strength of Butrans^® (buprenorphine) Transdermal System CIII. Five strengths of Butrans will now be available: 5 mcg/hour, 7.5 mcg/hour, 10 mcg/hour, 15 mcg/hour and 20 mcg/hour.  The Butrans Transdermal System is also approved to allow the use of two patches to facilitate dose adjustments during titration. The total dose from both patches should not exceed 20 mcg/hour. Purdue expects to launch Butrans 7.5 mcg/hour commercially in the United States in October 2014.

"This approval provides healthcare professionals another option to tailor Butrans therapy to the individual needs of appropriate chronic pain patients," said Todd Baumgartner, M.D., MPH, Vice President of Research & Development and Chief Medical Officer at Purdue Pharma L.P. "The introduction of the 7.5 mcg/hour dosage strength further demonstrates Purdue's ongoing commitment to the management of chronic pain." 

Butrans is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Butrans also has the following Limitations of Use: Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risk of overdose and death with extended-release opioid formulations, reserve Butrans for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Butrans is not indicated as an as-needed (prn) analgesic.

Butrans was approved by the FDA in 2010 in the following dosage strengths: 5 mcg/hour, 10 mcg/hour and 20 mcg/hour. Butrans is the first and only transdermal system that delivers a continuous release of buprenorphine for seven days. The active ingredient in Butrans Transdermal System is buprenorphine and a Schedule III controlled substance which means prescriptions for Butrans may be called into the pharmacy and refills provided up to five times in a six month period. Butrans has an abuse liability similar to other CIII opioids. For the use of two patches, patients should be instructed to remove their current patch and apply the two new patches adjacent to one another at a different application site.

The Full Prescribing Information for Butrans contains the following Boxed Warning:

WARNING: ADDICTION, ABUSE and MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; and NEONATAL OPIOID WITHDRAWAL SYNDROME

Addiction, Abuse, and Misuse
BUTRANS^® exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk prior to prescribing BUTRANS, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.1) and Overdosage (10)].

Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of BUTRANS.  Monitor for respiratory depression, especially during initiation of BUTRANS or following a dose increase. Misuse or abuse of BUTRANS by chewing, swallowing, snorting or injecting buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of buprenorphine and pose a significant risk of overdose and death [see Warnings and Precautions (5.2)].

Accidental Exposure
Accidental exposure to even one dose of BUTRANS, especially by children, can result in a fatal overdose of buprenorphine [see Warnings and Precautions (5.2)].

Neonatal Opioid Withdrawal Syndrome
Prolonged use of BUTRANS during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.3)].

Parentheses refer to sections in the Full Prescribing Information

CONTRAINDICATIONS

Butrans is contraindicated in patients with:

• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected paralytic ileus
• Hypersensitivity (e.g., anaphylaxis) to buprenorphine

WARNINGS AND PRECAUTIONS

• Addiction, Abuse, and Misuse

Butrans contains buprenorphine, a Schedule III controlled substance. Butrans exposes users to the risks of opioid addiction, abuse, and misuse. As modified-release products such as Butrans deliver the opioid over an extended period of time, there is a greater risk for overdose and death, due to the larger amount of buprenorphine present. Addiction can occur at recommended doses and if the drug is misused or abused. Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing Butrans, and monitor all patients during therapy for the development of these behaviors or conditions. Abuse or misuse of Butrans by placing it in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking, overdose and death.

• Life‐Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with modified-release opioids, even when used as recommended, and if not immediately recognized and treated, may lead to respiratory arrest and death. The risk of respiratory depression is greatest during the initiation of therapy or following a dose increase; therefore, closely monitor patients for respiratory depression. Proper dosing and titration of Butrans are essential. Overestimating the Butrans dose when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental exposure to Butrans, especially in children, can result in respiratory depression and death due to an overdose of buprenorphine.

• Neonatal Opioid Withdrawal Syndrome

Prolonged use of Butrans during pregnancy can result in neonatal opioid withdrawal syndrome which may be life-threatening to the neonate if not recognized and treated, and requires management according to protocols developed by neonatology experts.

• Interactions with Central Nervous System Depressants

Hypotension, profound sedation, coma, respiratory depression, or death may result if Butrans is used concomitantly with other CNS depressants, including alcohol or illicit drugs that can cause CNS depression. Start with Butrans 5 mcg/hour patch, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant.

• Use in Elderly, Cachectic, and Debilitated Patients and Patients with Chronic Pulmonary Disease

Closely monitor elderly, cachectic, and debilitated patients, and patients with chronic obstructive pulmonary disease because of the increased risk of life-threatening respiratory depression. Consider the use of alternative non-opioid analgesics in patients with chronic obstructive pulmonary disease if possible.

• 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.

• Hypotensive Effects

Butrans may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. Monitor patients during dose initiation or titration.

• Use in Patients with Head Injury or Increased Intracranial Pressure

Monitor patients taking Butrans who may be susceptible to the intracranial effects of CO₂ retention for signs of sedation and respiratory depression. Avoid the use of Butrans in patients with impaired consciousness or coma. 

• 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.

• Application of External Heat

Avoid exposing the Butrans application site and surrounding area to direct external heat sources. There is a potential for temperature‐dependent increases in buprenorphine released from the system resulting in possible overdose and death. 

• Use in Patients with Gastrointestinal Conditions

Avoid the use of Butrans in patients with paralytic ileus and other GI obstructions. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

ADVERSE REACTIONS

• Most common adverse reactions (≥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 Full Prescribing Information for Butrans, including the Medication Guide and Boxed Warning is available at www.purduepharma.com/butranspi and at www.butrans.com.

Butrans can be abused in a manner similar to other opioid agonists, legal or illicit. Purdue supports prescriber and patient education as part of a comprehensive approach to address misuse, abuse and diversion of opioid pain medicines, while ensuring that these medications remain accessible for appropriate patients with chronic pain. Information on the shared REMS is available at www.ER-LA-opioidREMS.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 chronic pain. Headquartered in Stamford, CT, Purdue 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.

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SOURCE Purdue Pharma L.P.