Important Safety Information
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 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)].
- 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
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
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Butrans and in those who obtain the drug illicitly. 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 receiving Butrans for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (eg, major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as Butrans, but use in such patients necessitates intensive counseling about the risks and proper use of Butrans, along with intensive monitoring for signs of addiction, abuse, or misuse
- 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
Opioid agonists such as Butrans are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Butrans. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug
Life-Threatening Respiratory Depression
- Serious, life-threatening, or fatal respiratory depression has been reported with the use of modified-release opioids, even when used as recommended, and if not immediately recognized and treated, 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 when initiating therapy with Butrans and following dose increases
- To reduce the risk of 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 withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, 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
Interactions With Central Nervous System Depressants
- Hypotension, profound sedation, coma, respiratory depression, and death may result if Butrans is used concomitantly with other CNS depressants (eg, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of Butrans in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient's response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient's use of alcohol or illicit drugs that cause CNS depression. If the decision to begin Butrans therapy is made, 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
- Closely monitor elderly, cachectic, and debilitated patients, since life-threatening respiratory depression is more likely to occur due to altered pharmacokinetics or clearance, particularly when initiating and titrating Butrans and when given concomitantly with other drugs that depress respiration
Use in Patients With Chronic Pulmonary Disease
- When initiating therapy and titrating with Butrans, 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. In these patients, even usual therapeutic doses of Butrans may decrease respiratory drive to the point of apnea. Consider the use of alternative non-opioid analgesics in these patients if possible
- A positive-controlled study of the effects of Butrans on the QTc interval in healthy subjects demonstrated no clinically meaningful effect at a Butrans dose of 10 mcg/hour; however, a Butrans dose of 40 mcg/hour (given as two Butrans 20 mcg/hour Transdermal Systems) was observed to prolong the QTc interval
Consider these observations in clinical decisions when prescribing Butrans to patients with hypokalemia or clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia. Avoid the use of Butrans in patients with a history of Long QT Syndrome or an immediate family member with this condition, or those taking Class IA antiarrhythmic medications (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (eg, sotalol, amiodarone, dofetilide)
- Butrans may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration with certain CNS depressant drugs (eg, phenothiazines or general anesthetics). Monitor these patients for signs of hypotension after initiating or titrating the dose of Butrans
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 (eg, those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with Butrans. Butrans may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of Butrans in patients with impaired consciousness or coma
- Although not observed in Butrans chronic pain clinical trials, cases of cytolytic hepatitis and hepatitis with jaundice have been observed in individuals receiving sublingual buprenorphine for the treatment of opioid dependence, both in clinical trials and in post-marketing adverse event reports. For patients at increased risk of hepatotoxicity, obtain baseline liver enzyme levels and monitor periodically and during treatment with Butrans
Application Site Skin Reactions
- In rare cases, severe application site skin reactions with signs of marked inflammation including "burn," "discharge," and "vesicles" have occurred. Time of onset varies, ranging from days to months following the initiation of Butrans treatment. Instruct patients to promptly report the development of severe application site reactions and discontinue therapy
- Cases of acute and chronic hypersensitivity to buprenorphine have been reported both in clinical trials and in the post-marketing experience. The most common signs and symptoms include rashes, hives, and pruritus. Cases of bronchospasm, angioneurotic edema, and anaphylactic shock have been reported. A history of hypersensitivity to buprenorphine is a contraindication to the use of Butrans
Application of External Heat
- Advise patients and their caregivers to avoid exposing the Butrans application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, saunas, hot tubs, and heated water beds while wearing the system because an increase in absorption of buprenorphine may occur. Advise patients against exposure of the Butrans application site and surrounding area to hot water or prolonged exposure to direct sunlight. There is a potential for temperature-dependent increases in buprenorphine released from the system resulting in possible overdose and death
Patients With Fever
- Monitor patients wearing Butrans systems who develop fever or increased core body temperature due to strenuous exertion for opioid side effects and adjust the Butrans dose if signs of respiratory or central nervous system depression occur
Use in Patients With Gastrointestinal Conditions
- Butrans is contraindicated in patients with paralytic ileus. Avoid the use of Butrans in patients with other GI obstruction. Butrans may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause increases in the serum amylase
Use in Patients With Convulsive or Seizure Disorders
- Butrans may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during Butrans therapy
Driving and Operating Machinery
- Butrans may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of Butrans and know how they will react to the medication
Use in Addiction Treatment
- Butrans has not been studied and is not approved for use in the management of addictive disorders
Most common adverse reactions (≥5%) reported by patients treated with Butrans in 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.
Reference: 1. Steiner D, Munera C, Hale M, Ripa S, Landau C. Efficacy and safety of buprenorphine transdermal system (BTDS) for chronic moderate to severe low back pain: a randomized, double-blind study. J Pain. 2011;12:1163-1173.
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 healthcare professionals of the United States of America only. ©2014 Purdue Pharma L.P., Stamford, CT 06901-3431