Important Safety Information
WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE
Butrans contains buprenorphine, an opioid agonist and Schedule III controlled substance with an abuse liability similar to other Schedule III opioids, legal or illicit [see Warnings and Precautions (5.1)]. Assess each patient's risk for opioid abuse or addiction prior to prescribing Butrans. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depressive disorder). Routinely monitor all patients receiving Butrans for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and Dependence (9)].
Life-Threatening Respiratory Depression
Respiratory depression, including fatal cases, may occur with use of Butrans, even when the drug has been used as recommended and not misused or abused [see Warnings and Precautions (5.2)]. Proper dosing and titration are essential and Butrans should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Monitor for respiratory depression, especially during initiation of Butrans or following a dose increase.
Accidental exposure to Butrans, especially in children, can result in a fatal overdose of buprenorphine [see Warnings and Precautions (5.3)].
Parentheses refer to sections in the Full Prescribing Information.
Administration of Butrans
- Butrans is for transdermal use (on intact skin) only. Each Butrans Transdermal System is intended to be worn for 7 days
- Instruct patients not to use Butrans if the pouch seal is broken or the patch is cut, damaged, or changed in any way and not to cut Butrans
- Instruct patients to apply immediately after removal from the individually sealed pouch
- Apply Butrans to the upper outer arm, upper chest, upper back or the side of the chest. These 4 sites (each present on both sides of the body) provide 8 possible application sites. Rotate Butrans among the 8 described skin sites. After Butrans removal, wait a minimum of 21 days before reapplying to the same skin site
- Apply Butrans to a hairless or nearly hairless skin site. If none are available, the hair at the site should be clipped, not shaven. Do not apply Butrans to irritated skin. If the application site must be cleaned, clean the site with water only. Do not use soaps, alcohol, oils, lotions, or abrasive devices. Allow the skin to dry before applying Butrans
- If problems with adhesion of Butrans occur, the edges may be taped with first aid tape. If Butrans falls off during the 7 days dosing interval, dispose of the transdermal system properly and place a new Butrans Transdermal System on at a different skin site
- If the buprenorphine-containing adhesive matrix accidentally contacts the skin, instruct patients or caregivers to wash the area with water and not to use soap, alcohol, or other solvents to remove the adhesive because they may enhance the absorption of the drug
- See the Instructions for Use for step-by-step instructions for applying Butrans
- 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 (eg, anaphylaxis) to buprenorphine
WARNINGS AND PRECAUTIONS
- Abuse Potential: Buprenorphine can be abused in a manner similar to other opioid agonists, legal or illicit. Assess risk for opioid abuse or addiction prior to prescribing. Routinely monitor all patients for signs of misuse, abuse, and addiction. Addiction can occur even under appropriate medical use. Misuse or abuse of Butrans by chewing, swallowing, snorting or injecting buprenorphine extracted from the transdermal system will result in the uncontrolled delivery of the opioid and pose a significant risk that could result in overdose and death
- Life-Threatening Respiratory Depression: Respiratory depression is the primary risk of Butrans and may lead to respiratory arrest and death. While serious,
life-threatening, or fatal respiratory depression can occur at any time during the use of Butrans, the risk is greatest during the initiation of therapy or following a dose increase. 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: Accidental exposure to Butrans, especially in children, can result in a fatal overdose
- Elderly, Cachectic, and Debilitated Patients: Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics. Monitor such patients closely, particularly when initiating and titrating Butrans and when Butrans is given concomitantly with other drugs that depress respiration
- Use in Patients with Chronic Pulmonary Disease: Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression for respiratory depression, particularly when initiating therapy and titrating with Butrans. Even usual therapeutic doses of Butrans may decrease respiratory drive to the point of apnea
- Interactions with Alcohol, CNS Depressants, and Illicit Drugs: Hypotension, profound sedation, coma or respiratory depression may result if Butrans is added to a regimen that includes other CNS depressants, alcohol, 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
- Hypotensive Effects: Butrans may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. Monitor patients after initiating or titrating
- Use in Patients with Head Injury or Increased Intracranial Pressure: Monitor patients who may be susceptible to the intracranial effects of CO2 retention for signs of sedation and respiratory depression, particularly when initiating therapy with Butrans. Opioids may also obscure the clinical course in a patient with a head injury
- 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
- Avoidance of Withdrawal: When discontinuing Butrans, gradually taper the dose. Do not abruptly discontinue Butrans
- 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
Please read the Full Prescribing Information, including Boxed Warning.
To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch.
Intended for patients of the United States of America only. ©2013 Purdue Pharma L.P., Stamford, CT 06901-3431