Buprenorphine

2 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, 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 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. ( 2.1 , 5 ) Initiate the dosing regimen for each patient 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 buprenorphine transdermal system. 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 buprenorphine transdermal system 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 buprenorphine transdermal system, 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 buprenorphine transdermal system 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 buprenorphine transdermal system 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 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, 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 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 )]. Buprenorphine transdermal system is for transdermal use (on intact skin) only. Each buprenorphine transdermal system patch is intended to be worn for 7 days. 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 )]. 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 buprenorphine transdermal system. Use of Buprenorphine Transdermal System in Patients who are not Opioid Tolerant Unless otherwise listed below, initiate treatment with buprenorphine transdermal system with a 5 mcg/hour patch. Conversion from Other Opioid Analgesics to Buprenorphine Transdermal System When buprenorphine transdermal system 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 buprenorphine transdermal system 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 buprenorphine transdermal system. Then initiate treatment with buprenorphine transdermal system 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 buprenorphine transdermal system is attained. Prior Total Daily Dose of Opioid Greater than 80 mg of Oral Morphine Equivalents per Day : Buprenorphine transdermal system 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 Buprenorphine Transdermal System Dose Conversion from Methadone to Buprenorphine Transdermal System 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. image description 2.4 Titration and Maintenance of Therapy Individually titrate buprenorphine transdermal system to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving buprenorphine transdermal system 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 buprenorphine transdermal system titration interval is 72 hours, based on the pharmacokinetic profile and time to reach steady state levels [see Clinical Pharmacology ( 12.3 )] . The maximum buprenorphine transdermal system dose is 20 mcg/hour. Do not exceed a dose of one 20 mcg/hour buprenorphine transdermal system due to the risk of QTc interval prolongation. In a clinical trial, buprenorphine transdermal system 40 mcg/hour (given as two buprenorphine transdermal system 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 buprenorphine transdermal system 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 buprenorphine transdermal system 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, buprenorphine transdermal system 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 Buprenorphine Transdermal System Do not rapidly reduce or abruptly discontinue buprenorphine transdermal system 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 buprenorphine transdermal system, there are a variety of factors that should be considered, including the total daily dose of opioid (including buprenorphine transdermal system) 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 buprenorphine transdermal system 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 Buprenorphine transdermal system has not been evaluated in patients with severe hepatic impairment. As buprenorphine transdermal system 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 Buprenorphine Transdermal System Instruct patients to apply immediately after removal from the individually sealed pouch. 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. See the Instructions for Use for step-by-step instructions for applying buprenorphine transdermal system. Apply buprenorphine transdermal system 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 buprenorphine transdermal system among the 8 described skin sites. After buprenorphine transdermal system removal, wait a minimum of 21 days before reapplying to the same skin site [see Clinical Pharmacology ( 12.3 )]. Apply buprenorphine transdermal system 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 buprenorphine transdermal system 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 buprenorphine transdermal system. Incidental exposure of the buprenorphine transdermal system patch to water, such as while bathing or showering is acceptable based on experience during clinical studies. If problems with adhesion of buprenorphine transdermal system 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 buprenorphine transdermal system falls off during the 7-day dosing interval, dispose of the transdermal system properly and place a new buprenorphine transdermal system patch on at a different skin site. When changing the system, instruct patients to remove buprenorphine transdermal system 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 buprenorphine transdermal system. Dispose of used and unused patches by following the instructions on the Patch-Disposal Unit that is packaged with the buprenorphine transdermal system 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.

See official label

1 INDICATIONS AND USAGE Buprenorphine transdermal system is indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate release opioids.