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AI-Generated response:

How is Buprenorphine used in patients with opioid use disorder?

Answer generated on June 4, 2024

The AI-generated responses are for illustration purposes only and should not be used for medical purposes.

Buprenorphine is used in opioid use disorder as a partial agonist at mu-opioid receptors and is available in forms such as sublingual tablets, films, and extended-release injections.

It is often combined with naloxone to prevent misuse.[1-5]

  • Buprenorphine should be initiated when patients are in mild to moderate withdrawal (COWS score of at least 11 to 12) to reduce the risk of precipitated withdrawal, typically 6-12 hours after short-acting opioids or 24-72 hours after long-acting opioids.[1]

  • The initial dose of sublingual buprenorphine/naloxone is typically 2 to 4 mg, with a first-day maximum of 8 mg, and optimized to a maintenance dose of 16-24 mg/day.[2]

  • Extended-release injectable forms like Sublocade and Brixadi are available for maintenance treatment, requiring initial stabilization on a transmucosal buprenorphine product.[3]

  • Common side effects include headache, anxiety, sweating, constipation, and sleep disturbances. Precipitated withdrawal can occur if buprenorphine is administered too soon after the last opioid use.[1-2]

  • Buprenorphine treatment should be part of a comprehensive treatment plan that includes counseling and psychosocial support.[4-5]

Additional info

Buprenorphine's effectiveness in opioid use disorder is enhanced by its ceiling effect at higher doses, which reduces the risk of respiratory depression, a common risk with full opioid agonists. The combination with naloxone, which is inactive when taken sublingually but active when injected, helps reduce the potential for intravenous misuse of buprenorphine. This combination is preferred except in cases where naloxone is contraindicated, such as in pregnant or lactating patients. The FDA has also approved long-acting injectable forms of buprenorphine, which can provide a steady state of medication and reduce the burden of daily dosing, thus improving compliance and reducing the risk of relapse. It is crucial to monitor patients for signs of sedation or intoxication and adjust the treatment regimen accordingly, especially when other CNS depressants are involved. The initiation and maintenance of buprenorphine treatment must be carefully managed to avoid complications such as precipitated withdrawal and to ensure therapeutic effectiveness.[1-5]

References

Reference 1

1.

Opioid Use Disorder, Elsevier ClinicalKey Clinical Overview

Treatment High affinity for μ-receptor; displaces full agonists (eg, morphine, methadone) and reduces their effects Can cause precipitated withdrawal if insufficient time has passed since last opioid dose Full agonists cannot displace buprenorphine Initiated when patients are in mild to moderate withdrawal to reduce risk of precipitated withdrawal Generally at least 6 to 12 hours after last use of heroin/short-acting opioids or 24 to 72 hours after last use of long-acting opioids (eg, methadone, fentanyl) COWS score of at least 11 to 12 (mild to moderate withdrawal) is indicative of sufficient level of withdrawal to start treatment (induction) with buprenorphine Once objective signs of withdrawal are confirmed, administer a dose of buprenorphine sufficient to suppress withdrawal symptoms Available forms include buprenorphine sublingual tablets and extended-release injection and buprenorphine-naloxone sublingual film and tablets or buccal film Combined buprenorphine-naloxone Preferred over buprenorphine monotherapy in most patients (except if allergic or in pregnant or lactating patients) Less likely to be misused or diverted; oral naloxone has poor bioavailability but becomes bioeffective if taken by IV and can precipitate withdrawal Generally well tolerated; adverse effects can include headache, anxiety, sweating, constipation, oral mucosal irritation, and sleep disturbance Discontinuation and tapering is a slow process (indefinite duration) and should be closely monitored; typically takes several months Ongoing maintenance treatment with buprenorphine is more effective in maintaining abstinence from opioids than tapering or discontinuation of buprenorphine therapy Naltrexone and extended-release naltrexone

Treatment Opioid agonist pharmacotherapy Buprenorphine Sublingual tablet Buprenorphine Hydrochloride Sublingual tablet; Adults: 2 to 4 mg SL as needed to achieve clinical effectiveness as rapidly as possible, then titrate dose by 2 to 4 mg to a level that holds the person in treatment and suppresses opioid withdrawal signs and symptoms. Target maintenance dose: 16 mg SL once daily. Usual dose range: 4 to 24 mg/day. Max: 32 mg/day. Buprenorphine-naloxone Sublingual film Buprenorphine Hydrochloride, Naloxone Hydrochloride Oral dissolving film; Adults: 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone SL once, initially; may titrate dose by 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone every 2 hours up to 8 mg/2 mg buprenorphine/naloxone on day 1 based on the control of acute withdrawal symptoms, then 16 mg/4 mg buprenorphine/naloxone SL once daily starting on day 2. Titrate dose by 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone to a level that holds the person in treatment and suppresses opioid withdrawal signs and symptoms. Target maintenance dose: 16 mg/4 mg buprenorphine/naloxone SL once daily. Usual dose range: 4 mg/1 mg/day to 24 mg/6 mg/day buprenorphine/naloxone. Max: 24 mg/6 mg/day buprenorphine/naloxone. Sublingual tablet

Reference 2

2.

Substance Use Disorder, Elsevier ClinicalKey Clinical Overview

Treatment Buprenorphine is a partial mu agonist with a maximal dose-effect ceiling that is below significant respiratory depression Provides relief from opioid withdrawal symptoms through agonist effect Naloxone is an opioid antagonist Not significantly bioavailable when taken sublingually or swallowed but exerts its effect and precipitates withdrawal when injected An initial dose of 2 to 4 mg of sublingual buprenorphine/naloxone is recommended, with first-day maximum of 8 mg, optimized over the next 2 to 3 days (optimal dosing 16-24 mg/day) Initiation dose must be well-timed to when the patient is already in moderate opioid withdrawal Clinical Opiate Withdrawal Scale is a clinician-administered tool that helps determine stage and severity of opioid withdrawal There is a risk of precipitated withdrawals in patients who have recently used full agonist opioids (eg, heroin, oxycodone) Higher doses of buprenorphine may be required in people using high-potency synthetic opioids, such as fentanyl A modified induction of buprenorphine may be required in people who use fentanyl due to its lipid solubility and delayed excretion patterns Methadone Primarily a µ-receptor agonist Provides relief from withdrawal symptoms through agonist effect Individualize dosing for each patient; there is substantial interpatient variability in the relative potency of different opioid drugs and products Acute withdrawal: typical initial oral dosing ranges from 10 to 30 mg; may administer an additional 5 to 10 mg PO after 2 to 4 hours if withdrawal symptoms have not been suppressed or if symptoms reappear Maintenance: usual oral dose range is 60 to 120 mg/day Tobacco use disorder FDA-approved medications include NRT (nicotine replacement therapy), bupropion, and varenicline Medication choice should be based on patient's profile and preference NRT 5 NRT options exist for the treatment of tobacco use disorder: OTC options include: Short-acting nicotine gum (2 and 4 mg)

Reference 3

3.

Buprenorphine, Elsevier ClinicalKey Drug Monograph Content last updated: May 5, 2024

Indications And Dosage NOTE: Before Sublocade use, persons should first undergo induction and stabilization by initiating a buprenorphine-containing product, delivering the equivalent of 8 to 24 mg/day of transmucosal buprenorphine for a minimum of 7 days. Subcutaneous dosage (Sublocade extended-release injection) for initiation of treatment after induction Adults: 300 mg subcutaneously once monthly for 2 months, then 100 mg subcutaneously once monthly. May increase the dose to 300 mg subcutaneously once monthly for persons who tolerate the 100 mg dose, but do not demonstrate a satisfactory clinical response, as evidenced by self-reported illicit opioid use or urine drug screens positive for illicit opioid use. A 2-month dosing interval may be considered in certain situations (e.g., extended travel) for persons established on 100 mg/month; in these instances, administer 300 mg subcutaneously once to cover the 2-month period, then resume 100 mg subcutaneously once monthly. Subcutaneous dosage (Sublocade extended-release injection) for transition from long-term treatment with transmucosal buprenorphine Adults: 300 mg subcutaneously once monthly for 1 month, then 100 mg subcutaneously once monthly for 8 to 18 mg/day of transmucosal buprenorphine and may consider 300 mg as the second dose in persons who experience craving or withdrawal symptoms after the initial 300 mg dose; 300 mg subcutaneously once monthly for 2 months, then 100 mg subcutaneously once monthly for 20 to 24 mg/day of transmucosal buprenorphine.

Indications And Dosage NOTE: Before Brixadi use, patients not currently receiving buprenorphine treatment should be given a test dose of 4 mg of transmucosal buprenorphine to establish tolerability without precipitating withdrawal. Subcutaneous dosage (Brixadi extended-release injection for weekly use) for initiation of treatment after induction Adults: Give 16 mg Brixadi (weekly) subcutaneously. Within 3 days, administer an additional dose of 8 mg subcutaneously to achieve the recommended 24 mg/week. If needed, may administer an additional 8 mg, waiting at least 24 hours after the previous injection, for a total dose of 32 mg/week. Base subsequent weekly injections on the total dosage established during Week 1. Make dosage adjustments at weekly appointments. Max: 32 mg/week. MISSED DOSE (Brixadi weekly): Give the next dose as soon as possible. Administer Brixadi (weekly) in 7-day intervals.

Reference 4

4.

Food and Drug Administration (DailyMed). Buprenorphine and Naloxone. 2023. Publish date: December 4, 2023

Dosage And Administration 2 DOSAGE AND ADMINISTRATION Administer buprenorphine and naloxone sublingual tablet sublingually as a single daily dose. ( 2.1 ) Strongly consider prescribing naloxone at the time buprenorphine and naloxone sublingual tablet is initiated or renewed because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose. ( 2.2 ) To avoid precipitating withdrawal, induction with buprenorphine sublingual tablets should be undertaken when objective and clear signs of withdrawal are evident. After induction, doses of buprenorphine and naloxone sublingual tablets should be progressively adjusted to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms ( 2.3 ) The recommended target dosage of buprenorphine and naloxone sublingual tablet for maintenance is 16/4 mg. ( 2.3 ) Administer buprenorphine and naloxone sublingual tablets as directed in the Full Prescribing Information. ( 2.3 , 2.4 ) When discontinuing treatment, gradually taper to avoid signs and symptoms of withdrawal. ( 2.7 ) 2.1 Important Dosage and Administration Information Buprenorphine and naloxone sublingual tablet is administered sublingually as a single daily dose. Buprenorphine and naloxone sublingual tablets should be used in patients who have been initially inducted using buprenorphine sublingual tablets. Medication should be prescribed in consideration of the frequency of visits.

Warnings And Cautions Inform patients and caregivers of their options for obtaining 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, if naloxone is prescribed, how to treat with naloxone. Emphasize the importance of calling 911 or getting emergency medical help, even if naloxone is administered [see Patient Counseling Information (17) ]. 5.3 Managing Risks from Concomitant Use of Benzodiazepine or Other CNS Depressants Concomitant use of buprenorphine and benzodiazepines or other CNS depressants increases the risk of adverse reactions including overdose and death. Medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs. Prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to the opioid use disorder alone. As a routine part of orientation to buprenorphine treatment, educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, and alcohol. Develop strategies to manage use of prescribed or illicit benzodiazepines or other CNS depressants at initiation of buprenorphine treatment, or if it emerges as a concern during treatment. Adjustments to induction procedures and additional monitoring may be required.

Reference 5

5.

Food and Drug Administration (DailyMed). Buprenorphine and Naloxone Sublingual Film. 2024. Publish date: January 3, 2024

Warnings And Cautions Medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs. Prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to the opioid use disorder alone. As a routine part of orientation to buprenorphine treatment, educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, and alcohol. Develop strategies to manage use of prescribed or illicit benzodiazepines or other CNS depressants at initiation of buprenorphine treatment, or if it emerges as a concern during treatment. Adjustments to induction procedures and additional monitoring may be required. There is no evidence to support dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use in buprenorphine-treated patients. However, if a patient is sedated at the time of buprenorphine dosing, delay or omit the buprenorphine dose if appropriate. Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate. For patients in buprenorphine treatment, benzodiazepines are not the treatment of choice for anxiety or insomnia.

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