Buprenorphine patch (transdermal): uses, appearance and warnings

Buprenorphine transdermal system is indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions (5.1) ] , reserve opioid analgesics, including buprenorphine transdermal system, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Buprenorphine transdermal system is not indicated as an as-needed (prn) analgesic. Buprenorphine transdermal system is a partial opioid agonist indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. ( 1 ) Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including buprenorphine transdermal system for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. ( 1 , 5.1 ) Buprenorphine transdermal system is not indicated as an as-needed (prn) analgesic. ( 1 )

Buprenorphine transdermal system is a rectangular or square, beige-colored system consisting of a protective liner and functional layers. Buprenorphine transdermal system is available in five strengths: Buprenorphine transdermal system 5 mcg/hour (dimensions: 45 mm by 45 mm) Buprenorphine transdermal system 7.5 mcg/hour (dimensions: 58 mm by 45 mm) Buprenorphine transdermal system 10 mcg/hour (dimensions: 45 mm by 68 mm) Buprenorphine transdermal system 15 mcg/hour (dimensions: 59 mm by 72 mm) Buprenorphine transdermal system 20 mcg/hour (dimensions: 72 mm by 72 mm) Transdermal system: 5 mcg/hour, 7.5 mcg/hour, 10 mcg/hour, 15 mcg/hour, and 20 mcg/hour. ( 3 )

Buprenorphine Transdermal System is supplied in cartons containing 4 individually packaged systems and a pouch containing 4 Patch-Disposal Units. The systems are supplied in the strengths below: 5 mcg/hour: square, beige-colored adhesive patches measuring 45 mm by 45 mm. Each system is printed in blue with "Buprenorphine Transdermal System" and 5 mcg/hr. NDC 42858-750-40 7.5 mcg/hour : rectangular, beige-colored adhesive patches measuring 58 mm by 45 mm. Each system is printed in blue with the "Buprenorphine Transdermal System" and 7.5 mcg/hr. NDC 42858-353-40 10 mcg/hour: rectangular, beige-colored adhesive patches measuring 68 mm by 45 mm. Each system is printed in blue with the "Buprenorphine Transdermal System" and 10 mcg/hr. NDC 42858-493-40 15 mcg/hour : rectangular, beige-colored adhesive patches measuring 72 mm by 59 mm. Each system is printed in blue with the "Buprenorphine Transdermal System" and 15 mcg/hr. NDC 42858-586-40 20 mcg/hour : square, beige-colored adhesive patches measuring 72 mm by 72 mm. Each system is printed in blue with the "Buprenorphine Transdermal System" and 20 mcg/hr. NDC 42858-839-40 Store buprenorphine transdermal system securely and dispose of properly [see Patient Counseling Information (17) ] . Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

Buprenorphine transdermal system is contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.2) ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.10) ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.15) ] Hypersensitivity (e.g., anaphylaxis) to buprenorphine [see Warnings and Precautions (5.18) , Adverse Reactions (6) ] Significant respiratory depression ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus ( 4 ) Hypersensitivity to buprenorphine ( 4 )

Opioid-Induced Hyperalgesia and Allodynia : Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. ( 5.9 ) Life Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Regularly evaluate particularly during initiation and titration. ( 5.10 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.11 ) Severe Hypotension : Regularly evaluate during dose initiation and titration. Avoid use of buprenorphine transdermal system in patients with circulatory shock. ( 5.12 ) Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Monitor for sedation and respiratory depression. Avoid use of buprenorphine transdermal system in patients with impaired consciousness or coma. ( 5.13 ) 5.1 Addiction, Abuse, and Misuse Buprenorphine transdermal system contains buprenorphine, a Schedule III controlled substance. As an opioid, buprenorphine transdermal system exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9) ] . Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed buprenorphine transdermal system. Addiction can occur at recommended doses and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions (6.2) ] . Assess each patient's risk for opioid addiction, abuse, or misuse prior to prescribing buprenorphine transdermal system, and reassess all patients receiving buprenorphine transdermal system for the development of these behaviors and 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 (e.g., 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 opioids such as buprenorphine transdermal system but use in such patients necessitates intensive counseling about the risks and proper use of buprenorphine transdermal system, along with frequent reevaluation for signs of addiction, abuse, or misuse. Consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration (2.2) , Warnings and Precautions (5.2) ] . Abuse or misuse of buprenorphine transdermal system by placing it in the mouth, chewing it, swallowing it, or using it in ways other than indicated may cause choking, overdose, and death [see Overdosage (10) ] . Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing buprenorphine transdermal system. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and the proper disposal of unused drug. Contact local state professional licensing board or state-controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.2 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents, depending on the patient's clinical status [see Overdosage (10) ] . Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of buprenorphine transdermal system, the risk is greatest during the initiation of therapy or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of buprenorphine transdermal system are essential [see Dosage and Administration (2) ] . Overestimating the buprenorphine transdermal system dosage when converting patients from another opioid product can result in fatal overdose with the first dose. Accidental exposure to buprenorphine transdermal system, especially in children, can result in respiratory depression and death due to an overdose of buprenorphine. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose . Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration (2.5) ]. Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). …

The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1) ] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.2) ] Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.3) ] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4) ] Application Site Skin Reactions [see Warnings and Precautions (5.8) ] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions (5.9) ] Adrenal Insufficiency [see Warnings and Precautions (5.11) ] Severe Hypotension [see Warnings and Precautions (5.12) ] Hepatotoxicity [see Warnings and Precautions (5.14) ] Gastrointestinal Effects [see Warnings and Precautions (5.15) ] Seizures [see Warnings and Precautions (5.16) ] QTc Prolongation [see Warnings and Precautions (5.17) ] Anaphylactic …

Table 5 includes clinically significant drug interactions with buprenorphine transdermal system. Table 5: Clinically Significant Drug Interactions with Buprenorphine Transdermal System Benzodiazepines Clinical Impact: There have been a number of reports regarding coma and death associated with the misuse and abuse of the combination of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection of crushed buprenorphine tablets. Preclinical studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. Intervention: Regularly evaluate patients with concurrent use of buprenorphine transdermal system and benzodiazepines. …