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. L imitations 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.
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 )
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 rotat ion. ( 5.9 ) L i f e 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 ) A d r e na l Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.11 ) S e v e r e Hypotension : Regularly evaluate during dose initiation and titration. Avoid use of buprenorphine transdermal system in patients with circulatory shock. ( 5.12 ) Ri s k s 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 )
5.1Addiction, 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.
5.2Life-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.
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). Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered.
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. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.
5.3Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of buprenorphine transdermal system with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions ( 7 ) ] . If the decision is made to prescr
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Interactions
Table 5 Includes clinically significant drug interactions with buprenorphine transdermal system. Table 5: Significant Drug Interactions with Buprenorphine Transdermal System B e n z odiazepines C linical 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. I ntervention: 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.
B e n z odiazepines and Other Central Nervous System (CNS) Depressants C linical 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 )] . I ntervention: 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 C linical 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.
I ntervention: 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 C linical 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. I ntervention: 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 S er otonergic Drugs C linical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
I ntervention: 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-HT 3 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).
M onoamine Oxidase Inhibitors (MAOIs) C linical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions ( 5.2 )] I ntervention: 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 M ixed Agonist/Antagonist Opioid Analgesics C linical Impact: May reduce the analgesic effect of buprenorphine transdermal system and/or precipitate withdrawal symptoms.
I ntervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine M u scle Relaxants C linical Impact: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. I ntervention: Because respiratory depression may be greater than otherwise expected, decrease the dosage of buprenorphine transdermal system and/or the muscle relaxant as necessary.
Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 , 5.3 )]. Diuretics C linical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. I ntervention: Evaluate patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs C linical Impact: The concomitant use of opioid analgesics, including buprenorphine, and anticholinergic drugs may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. I ntervention: Evaluate patients for signs of urinary retention or reduced gastric motility when buprenorphine transdermal system is used concomitantly with anticholinergic drugs. B e n z o dia ze p i n e s : May increase buprenorphine-induced respiratory depression.
Frequently evaluate patients on concurrent therapy closely. ( 7 ) C YP 3 A 4 Inhibitors/Inducers : Initiating CYP3A4 inhibitors or discontinuing CYP3A4 inducers may result in an increase in buprenorphine plasma concentrations. Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression. ( 7 ) S e ro t o n e r g i c Drugs : Concomitant use may result in serotonin syndrome.
Discontinue buprenorphine transdermal system if serotonin syndrome is suspected. ( 7 ) Mi x e d Agonist/Antagonist Analgesics : Avoid use with buprenorphine transde
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Pregnancy and breastfeeding
8.1Pregnancy
R isk 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.
C linical 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 )] . L abor 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 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 subcutaneous 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 subcutaneous 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 subcutaneous 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 subcutaneous buprenorphine was associated with toxicity to offspring. Buprenorphine was present in maternal milk. Pregnant rats were administered 1/4 of one buprenorphine transdermal system 5 mcg/hour every 3 days or received daily subcutaneous 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 subcutaneous 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.
Adverse reactions
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 Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 Double-Blind Treatment Period Titration 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 Double-Blind Treatment Period Titration 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 Placebo (N = 392) (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. The common (≥1% to <5%) adverse reactions reported by patients treated with buprenorphine transdermal system in the clinical trials organized by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class were: Gastrointestinal disorders : diarrhea, dyspepsia, and upper abdominal pain General disorders and administration site conditions : fatigue, peripheral edema, application site irritation, pain, pyrexia, chest pain, and asthenia I n fec tions and infestations : urinary tract infection, upper respiratory tract infection, nasopharyngitis, influenza, sinusitis, and bronchitis I njury, poisoning and procedural complications : fall Metabolism and nutrition disorders : anorexia Musculoskeletal and connective tissue disorders : back pain, arthralgia, pain in extremity, muscle spasms, musculoskeletal pain, joint swelling, neck pain, and myalgia Nervous system disorders : hypoesthesia, tremor, migraine, and paresthesia P s y c hiatric disorders : insomnia, anxiety, and depression R e spiratory, thoracic and mediastinal disorders : dyspnea, pharyngolaryngeal pain, and cough S kin and subcutaneous tissue disorders : pruritus, hyperhidrosis, rash, and generalized pruritus Vascular disorders : hypertension Other less common adverse reactions, including those known to occur with opioid treatment, that were seen in <1% of the patients in the buprenorphine transdermal system trials include the following in alphabetical order: Abdominal distention, abdominal pain, accidental injury, affect lability, agitation, alanine aminotransferase increased, angina pectoris, angioedema, apathy, application site dermatitis, asthma aggravated, bradycardia, chills, confusional state, contact dermatitis, coordination abnormal, dehydration, depersonalization, depressed level of consciousness, depressed mood, disorientation, disturbance in attention, diverticulitis, drug hypersensitivity, drug withdrawal syndrome, dry eye, dry skin, dysarthria, dysgeusia, dysphagia, euphoric mood, face edema, flatulence, flushing, gait disturbance, hallucination, hiccups, hot flush, hyperventilation, hypotension, hypoventilation, ileus, insomnia, libido decreased, loss of consciousness, malaise, memory impairment, mental impairment, mental status changes, miosis, muscle weakness, nervousness, nightmare, orthostatic hypotension, palpitations, psychotic disorder, respiration abnormal, respiratory depression, respiratory distress, respiratory failure, restlessness, rhinitis, sedation, sexual dysfunction, syncope, tachycardia, tinnitus, urinary hesitation, urinary incontinence, urinary retention, urticaria, vasodilatation, vertigo, vision blurred, visual disturbance, weight decreased, and wheezing.
6.2Postmarketing Experience
The following adverse reactions have been identified during post approval use of buprenorphine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. S er otonin syndrome : Cases of serotonin syndrome, a potentially life-threatening c
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Composition
Active ingredients
BUPRENORPHINE 20MCG/HR
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
If naloxone is prescribed, educate patients and caregivers on how to treat with naloxone [see Dosage and Administration ( 2.2 ) , Warnings and Precautions ( 5.1 , 5.3 ), Overdosage ( 10 )] .
