buprenorphine transdermal system
buprenorphine · Patch, Extended Release · Transdermal
Uses
Buprenorphine transdermal system is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. Limitations of Use Because of the risks of addiction, abuse and misuse with opioids, which can occur at any dosage or duration, and because of the greater risk of overdose and death with extended-release/long-acting opioid formulations [see Warnings and Precautions ( 5.1 )] , reserve buprenorphine transdermal system 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. 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 extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. ( 1 ) Limitations of Use ( 1 ) Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, and because of the greater risks of overdose and death with extended-release/long-acting opioid formulations, reserve buprenorphine transdermal system 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. Buprenorphine transdermal system is not indicated as an as-needed (prn) analgesic.
Dosage and administration
Buprenorphine transdermal system should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. ( 2.1 ) Buprenorphine transdermal system doses of 7.5 mcg/hour, 10 mcg/hour, 15 mcg/hour, and 20 mcg/hour are only for use in patients who are opioid experienced and in whom tolerance to an opioid of comparable potency has been established. Patients who are opioid-experienced are those receiving, for one week or longer, daily opioid doses up to 80 mg/day of oral morphine or an equianalgesic dose of another opioid. ( 2.1 ) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of buprenorphine transdermal system for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2 , 5 ) Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. ( 2.1 , 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with buprenorphine transdermal system. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2 , 5 ) Discuss availability of naloxone with the patient and caregiver and assess each patient’s need for access to naloxone, both when initiating and renewing treatment with buprenorphine transdermal system. Consider prescribing naloxone based on the patient’s risk factors for overdose. ( 2.2 , 5.1 , 5.2 , 5.3 , 10 ) For opioid-naïve patients, initiate treatment with a 5 mcg/hour patch. ( 2.1 ) Instruct patients to wear buprenorphine transdermal system for 7 days and to wait a minimum of 3 weeks before applying to the same site. ( 2.1 ) Do not abruptly discontinue buprenorphine transdermal system in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.5 ) 2.1 Important Dosage and Administration Information Buprenorphine transdermal system should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. Buprenorphine transdermal system doses of 7.5 mcg/hour, 10 mcg/hour, 15 mcg/hour, and 20 mcg/hour are only for use in patients who are opioid experienced and in whom tolerance to an opioid of comparable potency has been established. Patients who are opioid-experienced are those receiving, for one week or longer, daily opioid doses up to 80 mg/day of oral morphine or an equianalgesic dose of another opioid. Use the lowest effective dosage for the shortest duration of time consistent with individual patient’s treatment goals [see Warnings and Precautions ( 5 )] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of buprenorphine transdermal system for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ( 5.1 )] . Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with buprenorphine transdermal system. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions ( 5.2 )] . Instruct patients not to use buprenorphine transdermal system if the pouch seal is broken or the patch is cut, damaged, or changed in any way and not to cut buprenorphine transdermal system. Instruct patients to avoid exposing buprenorphine transdermal system to external heat sources, hot water, or prolonged direct sunlight [see Warnings and Precautions ( 5.6 )] . Buprenorphine transdermal system is for transdermal use (on intact skin) only. Each buprenorphine transdermal system patch is intended to be worn for 7 days. 2.2 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with buprenorphine transdermal system [see Warnings and Precautions ( 5.2 )] . Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see Warnings and Precautions ( 5.1 , 5.2 , 5.3 ), Overdosage ( 10 )] . Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. 2.3 Initial Dosage Use of Buprenorphine Transdermal System as the First Opioid Analgesic (opioid-naive patients) Initiate treatment with buprenorphine transdermal system with a 5 mcg/hour patch.
Dosage forms and strengths
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: 6.25 cm 2 ) Buprenorphine transdermal system 7.5 mcg/hour (dimensions: 9.375 cm 2 ) Buprenorphine transdermal system 10 mcg/hour (dimensions: 12.5 cm 2 ) Buprenorphine transdermal system 15 mcg/hour (dimensions: 18.75 cm 2 ) Buprenorphine transdermal system 20 mcg/hour (dimensions: 25 cm 2 ) Transdermal system: 5 mcg/hour, 7.5 mcg/hour, 10 mcg/hour, 15 mcg/hour, and 20 mcg/hour. ( 3 )
Contraindications
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 )
Warnings and precautions
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 Cranial 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 )] . Because extended-release products such as buprenorphine transdermal system 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 [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. 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 prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 ), Overdosage ( 10 )] . 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 antagonists, 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 Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with buprenorphine transdermal system.
Side effects
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/Allergic Reactions [see Warnings and Precautions ( 5.18 )] Most common adverse reactions (≥ 5%) include: nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alvogen, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 5,415 patients were treated with buprenorphine transdermal system in controlled and open-label chronic pain clinical trials. Nine hundred twenty-four subjects were treated for approximately six months and 183 subjects were treated for approximately one year. The clinical trial population consisted of patients with persistent moderate to severe pain. The most common serious adverse drug reactions (all <0.1%) occurring during clinical trials with buprenorphine transdermal system were: chest pain, abdominal pain, vomiting, dehydration, and hypertension/blood pressure increased. The most common adverse events (≥ 2%) leading to discontinuation were: nausea, dizziness, vomiting, headache, and somnolence. The most common adverse reactions (≥ 5%) reported by patients in clinical trials comparing buprenorphine transdermal system 10 mcg/hour or 20 mcg/hour to placebo are shown in Table 2, and comparing buprenorphine transdermal system 20 mcg/hour to buprenorphine transdermal system 5 mcg/hour are shown in Table 3 below: Table 2: Adverse Reactions Reported in ≥ 5% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Opioid-Naïve Patients Open-Label Titration Period Double-Blind Treatment Period Buprenorphine Transdermal System Buprenorphine Transdermal System Placebo MedDRA Preferred Term (N = 1024) (N = 256) (N = 283) Nausea 23% 13% 10% Dizziness 10% 4% 1% Headache 9% 5% 5% Application site pruritus 8% 4% 7% Somnolence 8% 2% 2% Vomiting 7% 4% 1% Constipation 6% 4% 1% Table 3: Adverse Reactions Reported in ≥ 5% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Opioid-Experienced Patients Open-Label Titration Period Double-Blind Treatment Period Buprenorphine Transdermal System Buprenorphine Transdermal System 20 Buprenorphine Transdermal System 5 MedDRA Preferred Term (N = 1160) (N = 219) (N = 221) Nausea 14% 11% 6% Application site pruritus 9% 13% 5% Headache 9% 8% 3% Somnolence 6% 4% 2% Dizziness 5% 4% 2% Constipation 4% 6% 3% Application site erythema 3% 10% 5% Application site rash 3% 8% 6% Application site irritation 2% 6% 2% The following table lists adverse reactions that were reported in at least 2.0% of patients in four placebo/active-controlled titration-to-effect trials. Table 4: Adverse Reactions Reported in Titration-to-Effect Placebo/Active-Controlled Clinical Trials with Incidence ≥ 2% MedDRA Preferred Term Buprenorphine Transdermal System (N = 392) Placebo (N = 261) Nausea 21% 6% Application site pruritus 15% 12% Dizziness 15% 7% Headache 14% 9% Somnolence 13% 4% Constipation 13% 5% Vomiting 9% 1% Application site erythema 7% 2% Application site rash 6% 6% Dry mouth 6% 2% Fatigue 5% 1% Hyperhidrosis 4% 1% Peripheral edema 3% 1% Pruritus 3% 0% Stomach discomfort 2% 0% The adverse reactions seen in controlled and open-label studies are presented below in the following manner: most common (≥ 5%), common (≥ 1% to < 5%), and less common (< 1%). The most common adverse reactions (≥ 5%) reported by patients treated with buprenorphine transdermal system in the clinical trials were nausea, headache, application site pruritus, dizziness, constipation, somnolence, vomiting, application site erythema, dry mouth, and application site rash.
Drug interactions
Table 5 Includes clinically significant drug interactions with buprenorphine transdermal system. Table 5: 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. Warn patients that it is extremely dangerous to self-administer benzodiazepines while taking buprenorphine transdermal system, and warn patients to use benzodiazepines concurrently with buprenorphine transdermal system only as directed by their physician. Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effects, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death [see Warnings and Precautions ( 5.3 )] . Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] . Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol. Inhibitors of CYP3A4 Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of buprenorphine transdermal system is achieved. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the buprenorphine plasma concentration will decrease [see Clinical Pharmacology ( 12.3 )] , potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to buprenorphine. Intervention: If concomitant use is necessary, consider dosage reduction of buprenorphine transdermal system until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4 inhibitor is discontinued, consider increasing the buprenorphine transdermal system dosage until stable drug effects are achieved. Assess for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inducers can decrease the plasma concentration of buprenorphine [see Clinical Pharmacology ( 12.3 )] , potentially resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the buprenorphine plasma concentration will increase [see Clinical Pharmacology ( 12.3 )] , which could increase or prolong both therapeutic effects and adverse reactions and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the buprenorphine transdermal system dosage until stable drug effects are achieved. Assess for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider buprenorphine transdermal system dosage reduction and evaluate patients at frequent intervals for signs of respiratory depression and sedation. Examples: Rifampin, carbamazepine, phenytoin Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue buprenorphine transdermal system if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions ( 5.2 )] Intervention: The use of buprenorphine transdermal system is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of buprenorphine transdermal system and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use.
Use in specific populations
Pregnancy : May cause fetal harm. ( 8.1 ) Lactation : Not recommended. ( 8.2 ) Severe Hepatic Impairment : Consider use of an alternate analgesic that may permit more flexibility in dosing. ( 8.6 ) 8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )] . Available data with buprenorphine transdermal system in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, buprenorphine caused an increase in the number of stillborn offspring, reduced litter size, and reduced offspring growth in rats at maternal exposure levels that were approximately 10 times that of human subjects who received one buprenorphine transdermal system 20 mcg/hour, the maximum recommended human dose (MRHD) [see Data] . Based on animal data, advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/neonatal adverse reactions Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.4 )]. Labor and Delivery Opioids cross the placenta and may produce respiratory depression in neonates. An opioid antagonist such as naloxone must be available for reversal of opioid-induced respiratory depression in the neonate. Buprenorphine transdermal system is not recommended for use in women immediately prior to labor, when shorter acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including buprenorphine transdermal system, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Data Animal Data Studies in rats and rabbits demonstrated no evidence of teratogenicity following buprenorphine transdermal system or subcutaneous (SC) administration of buprenorphine during the period of organogenesis. Rats were administered up to one buprenorphine transdermal system 20 mcg/hour every 3 days (Gestation Days 6, 9, 12, & 15) or received daily SC buprenorphine up to 5 mg/kg (Gestation Days 6 to 17). Rabbits were administered four buprenorphine transdermal system 20 mcg/hour every 3 days (Gestation Days 6, 9, 12, 15, 18, and 19) or received daily SC buprenorphine up to 5 mg/kg (Gestation Days 6 to 19). No teratogenicity was observed at any dose. AUC values for buprenorphine with buprenorphine transdermal system application and SC injection were approximately 110 and 140 times, respectively, that of human subjects who received the MRHD of one buprenorphine transdermal system 20 mcg/hour. In a pre- and post-natal study conducted in pregnant and lactating rats, administration of buprenorphine either as buprenorphine transdermal system or SC buprenorphine was associated with toxicity to offspring. Buprenorphine was present in maternal milk. Pregnant rats were administered ¼ of one buprenorphine transdermal system 5 mcg/hour every 3 days or received daily SC buprenorphine at doses of 0.05 mg/kg, 0.5 mg/kg, or 5 mg/kg from Gestation Day 6 to Lactation Day 21 (weaning). Administration of buprenorphine transdermal system or SC buprenorphine at 0.5 mg/kg or 5 mg/kg caused maternal toxicity and an increase in the number of stillborns, reduced litter size, and reduced offspring growth at maternal exposure levels that were approximately 10 times that of human subjects who received the MRHD of one buprenorphine transdermal system 20 mcg/hour. Maternal toxicity was also observed at the no observed adverse effect level (NOAEL) for offspring. 8.2 Lactation Risk Summary Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with buprenorphine transdermal system. Clinical Considerations Monitor infants exposed to buprenorphine through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of buprenorphine is stopped or when breast-feeding is stopped. 8.3 Females and Males of Reproductive Potential Infertility Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions ( 6.2 ), Preclinical Pharmacology ( 12.2 ), Nonclinical Toxicology ( 13.1 )] . 8.4 Pediatric Use The safety and efficacy of buprenorphine transdermal system in patients under 18 years of age has not been established. Buprenorphine transdermal system has been evaluated in an open-label clinical trial in pediatric patients. However, definitive conclusions are not possible because of the small sample size.
Overdosage
Clinical Presentation Acute overdosage with buprenorphine is manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 )] . Treatment of Overdose In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support measures. Opioid antagonists, such as naloxone, are specific antidotes to respiratory depression resulting from opioid overdose. However, naloxone may not be effective in reversing any respiratory depression produced by buprenorphine. High doses of naloxone, 10-35 mg/70 kg, may be of limited value in the management of buprenorphine overdose. The onset of naloxone effect may be delayed by 30 minutes or more. Doxapram hydrochloride (a respiratory stimulant) has also been used. Remove buprenorphine transdermal system immediately. Because the duration of reversal would be expected to be less than the duration of action of buprenorphine from buprenorphine transdermal system, carefully monitor the patient until spontaneous respiration is reliably re-established. Even in the face of improvement, continued medical monitoring is required because of the possibility of extended effects as buprenorphine continues to be absorbed from the skin. After removal of buprenorphine transdermal system, the mean buprenorphine concentrations decrease approximately 50% in 12 hours (range 10 to 24 hours) with an apparent terminal half-life of approximately 26 hours. Due to this long apparent terminal half-life, patients may require monitoring and treatment for at least 24 hours. In an individual physically dependent on opioids, administration of an opioid receptor antagonist may precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.
Description
Buprenorphine transdermal system is a transdermal system providing systemic delivery of buprenorphine, a mu opioid partial agonist analgesic, continuously for 7 days. The chemical name of buprenorphine is 6,14-ethenomorphinan-7-methanol, 17-(cyclopropylmethyl)- α-(1,1-dimethylethyl)-4, 5-epoxy-18, 19-dihydro-3-hydroxy-6-methoxy-α-methyl-, [5α, 7α, (S)]. The structural formula is: The molecular weight of buprenorphine is 467.6; the empirical formula is C 29 H 41 NO 4 . Buprenorphine occurs as a white or almost white powder and is very slightly soluble in water, freely soluble in acetone, soluble in methanol and ether, and slightly soluble in cyclohexane. The pKa is 8.5 and the melting point is about 217°C. System Components and Structure Five different strengths of buprenorphine transdermal system are available: 5 mcg/hour, 7.5 mcg/hour, 10 mcg/hour, 15 mcg/hour, and 20 mcg/hour (Table 6). The proportion of buprenorphine mixed in the adhesive matrix is the same in each of the five strengths. The amount of buprenorphine released from each system per hour is proportional to the active surface area of the system. The skin is the limiting barrier to diffusion from the system into the bloodstream. Table 6: Buprenorphine Transdermal System Product Specifications Buprenorphine Delivery Rate (mcg/hour) Active Surface Area (cm 2 ) Total Buprenorphine Content (mg) Buprenorphine Transdermal System 5 6.25 5 Buprenorphine Transdermal System 7.5 9.375 7.5 Buprenorphine Transdermal System 10 12.5 10 Buprenorphine Transdermal System 15 18.75 15 Buprenorphine Transdermal System 20 25 20 Buprenorphine transdermal system is a rectangular or square, beige-colored system consisting of a protective liner and functional layers. Proceeding from the outer surface toward the surface adhering to the skin, the layers are (1) a beige-colored web backing layer; (2) an adhesive rim without buprenorphine; (3) a separating layer over the buprenorphine-containing adhesive matrix; (4) the buprenorphine-containing adhesive matrix; and (5) a peel-off release liner. Before use, the release liner covering the adhesive layer is removed and discarded. Figure 1: Cross-Section Diagram of Buprenorphine Transdermal System (not to scale). The active ingredient in buprenorphine transdermal system is buprenorphine. The inactive ingredients in each system are: cross-linked polyacrylate, levulinic acid, oleyl oleate, and kollidon 90F.
How supplied
Buprenorphine transdermal system is supplied in cartons containing 4 individually packaged systems and a pouch containing 4 Patch-Disposal Units. Buprenorphine transdermal system 5 mcg/hour are square, beige-colored adhesive patches (dimensions: 6.25 cm 2 ). Each system is printed with the text “Buprenorphine Transdermal System CIII 5 mcg/hr” in black ink and is supplied in a 4-count carton ( NDC 47781-406-04 ) Buprenorphine transdermal system 7.5 mcg/hour are rectangular, beige-colored adhesive patches (dimensions: 9.375 cm 2 ). Each system is printed with the text “Buprenorphine Transdermal System CIII 7.5 mcg/hr” in black ink and is supplied in a 4-count carton ( NDC 47781-561-04 ) Buprenorphine transdermal system 10 mcg/hour are square, beige-colored adhesive patches (dimensions: 12.5 cm 2 ). Each system is printed with the text “Buprenorphine Transdermal System CIII 10 mcg/hr” in black ink and is supplied in a 4-count carton ( NDC 47781-407-04 ) Buprenorphine transdermal system 15 mcg/hour are rectangular, beige-colored adhesive patches (dimensions: 18.75 cm 2 ). Each system is printed with the text “Buprenorphine Transdermal System CIII 15 mcg/hr” in black ink and is supplied in a 4-count carton ( NDC 47781-419-04 ) Buprenorphine transdermal system 20 mcg/hour are square, beige-colored adhesive patches (dimensions: 25 cm 2 ). Each system is printed with the text “Buprenorphine Transdermal System CIII 20 mcg/hr” in black ink and is supplied in a 4-count carton ( NDC 47781-408-04 ) Store buprenorphine transdermal system securely and dispose of properly [see Patient Counseling Information ( 17 )] . Store at 25ºC (77ºF); excursions permitted between 15º to 30ºC (59º to 86ºF) [See USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide and Instructions for Use ). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store buprenorphine transdermal system securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving buprenorphine transdermal system unsecured can pose a deadly risk to others in the home [see Warnings and Precautions ( 5.1 , 5.2 ), Drug Abuse and Dependence ( 9.2 )] . Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Buprenorphine transdermal system patches can be disposed of by using the Patch-Disposal Unit [see Instructions for Use ] . Alternatively, expired, unwanted, or unused buprenorphine transdermal system should be disposed of by folding the patch in half and flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines. Addiction, Abuse, and Misuse Inform patients that the use of buprenorphine transdermal system, even when taken as recommended, can result in addiction, abuse, and misuse, which could lead to overdose and death [see Warnings and Precautions ( 5.1 )]. Instruct patients not to share buprenorphine transdermal system with others and to take steps to protect buprenorphine transdermal system from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting buprenorphine transdermal system or when the dosage is increased, and that it can occur even at recommended doses. 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 [see Warnings and Precautions ( 5.2 ), Overdosage ( 10 )] . Accidental Exposure Inform patients that accidental exposure, especially in children, may result in respiratory depression or death [see Warnings and Precautions ( 5.2 )] . Interaction with Benzodiazepines Warn patients that it is extremely dangerous to self-administer benzodiazepines while taking buprenorphine transdermal system, and warn patients to use benzodiazepines concurrently with buprenorphine transdermal system only as directed by their physician [see Drug Interactions ( 7 )] . Interaction with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if buprenorphine transdermal system is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [see Warnings and Precautions ( 5.3 )] . Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with buprenorphine transdermal system. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 )] . Educate patients and caregivers on how to recognize the signs and symptoms of an overdose. Explain to patients and caregivers that naloxone’s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered [see Overdosage ( 10 )] . If naloxone is prescribed, also advise patients and caregivers: How to treat with naloxone in the event of an opioid overdose To tell family and friends about their naloxone and to keep it in a place where family and friends can access it in an emergency To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do. Hyperalgesia and Allodynia Inform patients and caregivers not to increase opioid dosage without first consulting a clinician. Advise patients to seek medical attention if they experience symptoms of hyperalgesia, including worsening pain, increased sensitivity to pain, or new pain [see Warnings and Precautions ( 5.9 ), Adverse Reactions ( 6.2 )] . Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition called serotonin syndrome resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, or plan to take serotonergic medications [see Drug Interactions ( 7 )] . MAOI Interaction Inform patients to avoid taking buprenorphine transdermal system while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking buprenorphine transdermal system [see Drug Interactions ( 7 )] . Important Administration Instructions Instruct patients how to properly use buprenorphine transdermal system, including the following: 1. To carefully follow instructions for the application, removal, and disposal of buprenorphine transdermal system.
Label text from the FDA structured product label by Alvogen Inc. (revised Sep 12, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Buprenorphine in 5 products
buprenorphine transdermal system NDC products (5)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 47781-406 | Buprenorphine 5 ug/h Patch, Extended Release | Alvogen Inc. | ANDA · DEA CIII |
| 47781-407 | Buprenorphine 10 ug/h Patch, Extended Release | Alvogen Inc. | ANDA · DEA CIII |
| 47781-408 | Buprenorphine 20 ug/h Patch, Extended Release | Alvogen Inc. | ANDA · DEA CIII |
| 47781-419 | Buprenorphine 15 ug/h Patch, Extended Release | Alvogen Inc. | ANDA · DEA CIII |
| 58064-408 | Buprenorphine 20 ug/h Patch, Extended Release | LTS Therapy Systems, LLC | ANDA · DEA CIII |
Frequently asked questions
What is buprenorphine transdermal system used for?
Buprenorphine transdermal system is indicated for the management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate. Limitations of Use Because of the risks of addiction, abuse and misuse with opioids, which can occur at any dosage or duration, and because of the greater risk of overdose…
What are the side effects of buprenorphine transdermal system?
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… See the full label for the complete list.
Who makes buprenorphine transdermal system?
buprenorphine transdermal system is listed by 2 labelers in the FDA NDC directory, including Alvogen Inc., LTS Therapy Systems, LLC.