Butrans

Butrans is an FDA-registered drug product whose active ingredient is BUPRENORPHINE. It is labelled by Knoa Pharma LLC taken by transdermal and marketed as a human prescription drug product. Identifiers on file: NDC 59011-750, application NDA021306, label effective 20260501. It is one of 16 FDA drug label records sharing the active ingredient BUPRENORPHINE. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing BUPRENORPHINE are most often described in connection with: management severe, persistent pain, requires opioid, cannot adequately, alternative options, including immediate-release, opioids limitations, risks addiction. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE BUTRANS 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 BUTRANS, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. BUTRANS is not indicated as an as-needed (prn) analgesic. BUTRANS 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 BUTRANS, 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 ) BUTRANS is not indicated as an as-needed (prn) analgesic. ( 1 )

2 DOSAGE AND ADMINISTRATION BUTRANS 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 ) BUTRANS doses of 7.5, 10, 15, and 20 mcg/hour are only for use in patients 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 BUTRANS 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. ( 2.1 , 5 ) Initiate the dosing regimen for each patient's individually, taking into account the patients 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 BUTRANS. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.1 ) For patients who are not opioid tolerant, initiate treatment with a 5 mcg/hour patch. ( 2.1 ) Instruct patients to wear BUTRANS for 7 days and to wait a minimum of 3 weeks before applying to the same site. ( 2.1 ) Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with BUTRANS, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. ( 2.2 , 5.1 , 5.2 , 5.3 ) Periodically reassess patients receiving BUTRANS to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. ( 2.3 ) Do not rapidly reduce or abruptly discontinue BUTRANS in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.5 , 5.19 ) 2.1 Important Dosage and Administration Information BUTRANS 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. BUTRANS doses of 7.5, 10, 15, and 20 mcg/hour are only for use in patients who are 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 BUTRANS 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 BUTRANS. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions (5.2) ]. BUTRANS is for transdermal use (on intact skin) only. Each BUTRANS patch is intended to be worn for 7 days. Instruct patients not to use BUTRANS if the pouch seal is broken or the patch is cut, damaged, or changed in any way and not to cut BUTRANS. Instruct patients to avoid exposing BUTRANS to external heat sources, hot water, or prolonged direct sunlight [see Warnings and Precautions (5.6) ] . 2.2 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). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see Warnings and Precautions(5.1 , 5.2 , 5.3) ] . Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see Warnings and Precautions (5.2) ] . There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. 2.3 Initial Dosage It is safer to underestimate a patient's 24-hour oral buprenorphine dosage and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour buprenorphine dosage and manage an adverse reaction due to an overdose. While useful tables of opioid equivalents are readily available, there is inter-patient variability in the potency of opioid drugs and opioid formulations. Frequently reevaluate patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to BUTRANS. Use of BUTRANS in Patients who are not Opioid Tolerant Unless otherwise listed below, initiate treatment with BUTRANS with a 5 mcg/hour patch. Conversion from Other Opioid Analgesics to BUTRANS When BUTRANS therapy is initiated, discontinue all other opioid analgesics other than those used on an as-needed basis for breakthrough pain when appropriate. There is a potential for buprenorphine to precipitate withdrawal in patients who are already on opioids. Prior Total Daily Dose of Opioid Less than 30 mg of Oral Morphine Equivalents per Day : Initiate treatment with BUTRANS 5 mcg/hour at the next dosing interval (see Table 1 below, middle column). Prior Total Daily Dose of Opioid Between 30 mg to 80 mg of Oral Morphine Equivalents per Day: Taper the patient's current around-the-clock opioids for up to 7 days to no more than 30 mg of morphine or equivalent per day before beginning treatment with BUTRANS. Then initiate treatment with BUTRANS 10 mcg/hour at the next dosing interval (see Table 1 below, right column). Patients may use short-acting analgesics as needed until analgesic efficacy with BUTRANS is attained. Prior Total Daily Dose of Opioid Greater than 80 mg of Oral Morphine Equivalents per Day : BUTRANS 20 mcg/hour may not provide adequate analgesia for patients requiring greater than 80 mg/day oral morphine equivalents. Consider the use of an alternate analgesic. Table 1: Initial BUTRANS Dose Conversion from Methadone to BUTRANS Regular evaluation is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma. Table 1 2.4 Titration and Maintenance of Therapy Individually titrate BUTRANS to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving BUTRANS to assess the maintenance of pain control, signs and symptoms of opioid withdrawal and other adverse reactions, as well as reassessing for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1 , 5.19) ] . Frequent communication is important among the prescriber, other members of healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During use of opioid therapy for an extended period of time, periodically reassess the continued need for opioid analgesics. The minimum BUTRANS titration interval is 72 hours, based on the pharmacokinetic profile and time to reach steady state levels [see Clinical Pharmacology (12.3) ] . The maximum BUTRANS dose is 20 mcg/hour. Do not exceed a dose of one 20 mcg/hour BUTRANS system due to the risk of QTc interval prolongation. In a clinical trial, BUTRANS 40 mcg/hour (given as two BUTRANS 20 mcg/hour systems) resulted in prolongation of the QTc interval [see Warnings and Precautions (5.17) , Clinical Pharmacology (12.2) ]. Patients who experience breakthrough pain may require a dosage adjustment increase of BUTRANS or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the BUTRANS dose. If after increasing the dosage, unacceptable opioid- related adverse reactions are observed (including an increase in pain after dosage increase) consider reducing the dosage [see Warnings and Precautions (5) ]. Adjust the dosage to obtain an appropriate balance between the management of pain and opioid-related adverse reactions. Because steady-state plasma concentrations are achieved within 72 hours, BUTRANS dosage may be adjusted every 3 days. Dose adjustments may be made in 5 mcg/hour, 7.5 mcg/hour, or 10 mcg/hour increments by using no more than two patches of the 5 mcg/hour, or 7.5 mcg/hour, or 10 mcg/hour system(s). The total dose from both patches should not exceed 20 mcg/hour. For the use of two patches, instruct patients to remove their current patch, and apply the two new patches at the same time, adjacent to one another at a different application site [see Dosage and Administration (2.7) ]. 2.5 Safe Reduction or Discontinuation of BUTRANS Do not rapidly reduce or abruptly discontinue BUTRANS in patients who may be physically dependent on opioids. Rapid reduction or abrupt discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid reduction or abrupt discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking BUTRANS, there are a variety of factors that should be considered, including the total daily dose of opioid (including BUTRANS) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on BUTRANS who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.19) , Drug Abuse and Dependence (9.3) ] . 2.6 Patients with Hepatic Impairment BUTRANS has not been evaluated in patients with severe hepatic impairment. As BUTRANS is only intended for 7-day application, consider use of an alternate analgesic that may permit more flexibility with the dosing in patients with severe hepatic impairment [see Warnings and Precautions (5.14) , Use in Specific Populations (8.6) , Clinical Pharmacology (12.3) ]. 2.7 Administration of BUTRANS Instruct patients to apply immediately after removal from the individually sealed pouch. Instruct patients not to use BUTRANS if the pouch seal is broken or the patch is cut, damaged, or changed in any way. See the Instructions for Use for step-by-step instructions for applying BUTRANS. Apply BUTRANS to the upper outer arm, upper chest, upper back or the side of the chest. These 4 sites (each present on both sides of the body) provide 8 possible application sites. Rotate BUTRANS among the 8 described skin sites. After BUTRANS removal, wait a minimum of 21 days before reapplying to the same skin site [see Clinical Pharmacology (12.3) ]. Apply BUTRANS to a hairless or nearly hairless skin site. If none are available, the hair at the site should be clipped, not shaven. Do not apply BUTRANS to irritated skin. If the application site must be cleaned, clean the site with water only. Do not use soaps, alcohol, oils, lotions, or abrasive devices. Allow the skin to dry before applying BUTRANS. Incidental exposure of the BUTRANS patch to water, such as while bathing or showering is acceptable based on experience during clinical studies. If problems with adhesion of BUTRANS occur, the edges may be taped with first aid tape. If problems with lack of adhesion continue, the patch may be covered with waterproof or semipermeable adhesive dressings suitable for 7 days of wear. If BUTRANS falls off during the 7-day dosing interval, dispose of the transdermal system properly and place a new BUTRANS patch on at a different skin site. When changing the system, instruct patients to remove BUTRANS and dispose of it properly [see Dosage and Administration (2.8) ] . If the buprenorphine-containing adhesive matrix accidentally contacts the skin, instruct patients or caregivers to wash the area with water and not to use soap, alcohol, or other solvents to remove the adhesive because they may enhance the absorption of the drug. 2.8 Disposal Instructions Patients should refer to the Instructions for Use for proper disposal of BUTRANS. Dispose of used and unused patches by following the instructions on the Patch-Disposal Unit that is packaged with the BUTRANS patches. Alternatively, patients can dispose of used patches by folding the adhesive side of the patch to itself, then flushing the patch down the toilet immediately upon removal. Unused patches should be removed from their pouches, the protective liners removed, the patches folded so that the adhesive side of the patch adheres to itself, and immediately flushed down the toilet. Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed.

4 CONTRAINDICATIONS BUTRANS 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 )

6 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 Knoa Pharma LLC at 1-888-726-7535 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 BUTRANS 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 BUTRANS 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 BUTRANS 10 or 20 mcg/hour to placebo are shown in Table 2, and comparing BUTRANS 20 mcg/hour to BUTRANS 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: Patients who were not Opioid Tolerant Open-Label Titration Period Double-Blind Treatment Period BUTRANS BUTRANS 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 BUTRANS BUTRANS 20 BUTRANS 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 BUTRANS (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 BUTRANS 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 BUTRANS 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 Infections and infestations : urinary tract infection, upper respiratory tract infection, nasopharyngitis, influenza, sinusitis, and bronchitis Injury, 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 Psychiatric disorders : insomnia, anxiety, and depression Respiratory, thoracic and mediastinal disorders : dyspnea, pharyngolaryngeal pain, and cough Skin 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 BUTRANS 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. 6.2 Postmarketing 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. Serotonin syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis : Anaphylaxis has been reported with ingredients contained in BUTRANS. Androgen deficiency : Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see Clinical Pharmacology (12.2) ] . Hyperalgesia and Allodynia : Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and Precautions (5.9) ]. Hypoglycemia : Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes). Opioid-induced esophageal dysfunction (OIED ): Cases of OIED have been reported in patients taking opioids and may occur more frequently in patients taking higher doses of opioids, and/or in patients taking opioids longer term [see Warnings and Precautions (5.15) ]. Adverse Reactions from Observational Studies A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021. Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90-day period (n=978); or 2) filled any Schedule II opioid analgesic prescriptions covering at least 70 of 90 days (n=1,244). Those included also had no dispensing of the qualifying opioids in the previous 6 months. Over 12 months: approximately 1% to 6% of participants across the two cohorts newly met criteria for addiction, as assessed with two validated interview-based measures of moderate-to-severe opioid use disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and approximately 9% and 22% of participants across the two cohorts newly met criteria for prescription opioid abuse and misuse [defined in Drug Abuse and Dependence (9.2)], respectively, as measured with a validated self-reported instrument. A retrospective, observational cohort study estimated the risk of opioid- involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249). Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days' supply over the 3 months prior to study entry and none during the preceding 6 months. Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-based algorithm with linkage to the National Death Index database. The 5-year cumulative incidence estimates for opioid-involved overdose or opioid overdose-related death ranged from approximately 1.5% to 4% across study sites, counting only the first event during follow-up. Approximately 17% of first opioid overdoses observed over the entire study period (5-11 years, depending on the study site) were fatal. Higher baseline opioid dose was the strongest and most consistent predictor of opioid-involved overdose or opioid overdose-related death. Study exclusion criteria may have selected patients at lower risk of overdose, and substantial loss to follow-up (approximately 80%) also may have biased estimates. The risk estimates from the studies described above may not be generalizable to all patients receiving opioid analgesics, such as those with exposures shorter or longer than the duration evaluated in the studies.

FDA lists 16 drug label records with BUPRENORPHINE as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

What is Butrans used for?
1 INDICATIONS AND USAGE BUTRANS 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 …

Who makes Butrans?
Knoa Pharma LLC is the labeler of record for Butrans. 16 FDA label records share the active ingredient BUPRENORPHINE, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does Butrans come in?
administered by transdermal. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is Butrans prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing BUPRENORPHINE?
Yes. 16 FDA drug label records list BUPRENORPHINE as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has Butrans been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.