Buprenorphine Dosage

Medically reviewed by Drugs.com. Last updated on Mar 5, 2024.

Usual Adult Dose for Opioid Use Disorder - Induction

SUBLINGUAL TABLETS:
Initial Dose: 2 to 4 mg sublingually, then observe for signs of precipitated withdrawal

• If 60 to 90 minutes elapse without onset of withdrawal symptoms: Additional doses can be administered in increments of 2 to 8 mg.
• After establishing the initial dose is well tolerated: The dose can be increased fairly rapidly until effects stabilize for 24 hours and clinical efficacy is attained.

Comments:

• This product is preferred for induction; after induction, buprenorphine-naloxone sublingual film or tablets are preferred (due to the naloxone component) when clinical use includes unsupervised administration.
• The use of this product for unsupervised administration should be limited to patients who cannot tolerate buprenorphine-naloxone sublingual film or tablets (e.g., known hypersensitivity to naloxone).
• Before induction, type of opioid dependence (i.e., long- or short-acting opioid products), time since last opioid use, and degree/level of opioid dependence should be considered.
• The first dose of this product should be administered only when objective and clear signs of moderate opioid withdrawal appear, and:
• At least 4 hours have elapsed since last use of heroin or other short-acting opioids
• At least 24 hours (in general) have elapsed since last use of methadone or other long-acting opioids
• According to some experts: Initiation of this drug should generally occur at least 6 to 12 hours after the last use of heroin or other short-acting opioids, and 24 to 72 hours after the last use of long-acting opioids such as methadone.
• Patients dependent on heroin or other short-acting opioids:
• An adequate treatment dose, titrated to clinical efficacy, should be achieved as rapidly as possible; dosing on the initial day of therapy may be given in 2 to 4 mg increments (if preferred).
• In some studies, gradual induction over several days led to a high dropout rate during the induction period.
• In a 1-month study, patients received 8 mg of this product on Day 1 and 16 mg of this product on Day 2; from Day 3 onward, patient received either buprenorphine-naloxone sublingual tablets or this product at the same buprenorphine dose as Day 2 (based on assigned treatment).
• Induction in the studies of buprenorphine solution was accomplished over 3 to 4 days, depending on target dose.
• Patients dependent on methadone or other long-acting opioids:
• These patients may be more susceptible to precipitated and prolonged withdrawal during induction than those on short-acting opioids.
• There is little controlled experience with the transfer of methadone-maintained patients to this drug; available evidence suggests that withdrawal signs/symptoms are possible during induction onto this drug.
• Withdrawal appears more likely in patients maintained on higher doses of methadone (greater than 30 mg) and when the first dose of this drug is administered shortly after the last methadone dose.

Use: For the treatment of opioid dependence

Usual Adult Dose for Opioid Use Disorder - Maintenance

SUBCUTANEOUS INJECTION:
BRIXADI:
Patients Not Currently Receiving Buprenorphine Treatment:

• Week 1: 24 mg subcutaneously of the weekly formulation, titrated up over the first week of therapy as follows:
• To avoid precipitating an opioid withdrawal syndrome, administer a test dose of transmucosal buprenorphine 4 mg when objective signs of mild to moderate withdrawal appear.
• If the transmucosal buprenorphine dose is tolerated without precipitated withdrawal, administer the first dose of the weekly formulation, 16 mg.
• Administer an additional 8 mg dose of the weekly formulation within 3 days of the first dose to achieve the recommended 24 mg dose.
• During this first week of therapy (if needed): Administer an additional 8 mg dose of the weekly formulation (waiting at least 24 hours after the previous injection) for a total weekly dose of 32 mg.
• Week 2 onwards: Administer subsequent doses based on the total weekly dose established during Week 1.
• Dosage adjustments can be made at weekly appointments.
• Maximum dose: 32 mg subcutaneously once a week

Patients Switching from Transmucosal Buprenorphine-Containing Products to the Weekly Formulation:

• For 6 mg/day or less of sublingual buprenorphine: 8 mg subcutaneously once a week
• For 8 to 10 mg/day of sublingual buprenorphine: 16 mg subcutaneously once a week
• For 12 to 16 mg/day of sublingual buprenorphine: 24 mg subcutaneously once a week
• For 18 to 24 mg/day of sublingual buprenorphine: 32 mg subcutaneously once a week

Patients Switching from Transmucosal Buprenorphine-Containing Products to the Monthly Formulation:

• For 8 to 10 mg/day of sublingual buprenorphine: 64 mg subcutaneously once a month
• For 12 to 16 mg/day of sublingual buprenorphine: 96 mg subcutaneously once a month
• For 18 to 24 mg/day of sublingual buprenorphine: 128 mg subcutaneously once a month

Patients Transitioning Between the Weekly and Monthly Formulations:

• Weekly dose 16 mg: Monthly dose 64 mg
• Weekly dose 24 mg: Monthly dose 96 mg
• Weekly dose 32 mg: Monthly dose 128 mg

Duration of Maintenance Therapy: No maximum is recommended.

• Treatment may continue indefinitely for some patients.

Patient Selection:
Appropriate patients for the weekly formulation are those who:

• Have tolerated a single 4 mg dose of a transmucosal buprenorphine-containing product
• The test dose should be administered based on instructions in the appropriate manufacturer product information.
• Are currently being treated with a transmucosal buprenorphine-containing product

Appropriate patients for the monthly formulation are those who are currently being treated with a transmucosal buprenorphine-containing product.

• The monthly formulation is not intended for patients not currently receiving buprenorphine treatment.

SUBLOCADE:
Initiation of Treatment After Induction:

• Initial Dose: 300 mg subcutaneously once a month for the first 2 months
• Maintenance dose: 100 mg subcutaneously once a month
• If 100 mg dose is tolerated but a satisfactory clinical response is not shown (self-reported illicit opioid use, urine drugs screens positive for illicit opioid use): May increase to 300 mg subcutaneously once a month

Transition of Patients Established on Long-Term Therapy with Transmucosal Buprenorphine Whose Disease Symptoms are Controlled:

• For 8 to 18 mg/day of transmucosal buprenorphine:
• Injection 1: 300 mg subcutaneously
• Injection 2: 100 mg subcutaneously; if craving or withdrawal symptoms are still present after the initial 300 mg dose, consider administering 300 mg as the second dose.
• Maintenance Dose: 100 mg subcutaneously once a month
• For 20 to 24 mg/day of transmucosal buprenorphine:
• Injection 1 and 2: 300 mg subcutaneously
• Maintenance Dose: 100 mg subcutaneously once a month

Duration of Maintenance Therapy: No maximum is recommended.

• Treatment may continue indefinitely for some patients.

SUBDERMAL IMPLANT: Insert 1 dose subdermally in the inner side of the upper arm.

• This product is intended to be in place for 6 months; remove implants by the end of the sixth month.
• If continued treatment is desired at the end of the first 6-month treatment cycle:
• Insert new implants subdermally in the contralateral arm at time of removal.
• If new implants are not inserted on the same day as the removal, maintain patients on their previous dosage of transmucosal buprenorphine (i.e., the dose from which they were transferred) before additional treatment with this product.
• For patients who feel they need ongoing supplemental dosing with transmucosal buprenorphine: Consider alternate buprenorphine products for maintenance of treatment.

Patient Selection:
This product is only for use in opioid-tolerant patients who meet ALL of the following criteria:

• Achieved and sustained prolonged clinical stability on transmucosal buprenorphine
• Currently on a maintenance dose of 8 mg/day or less of a buprenorphine (Subutex) or buprenorphine-naloxone (Suboxone) sublingual tablet or its transmucosal buprenorphine product equivalent (transmucosal buprenorphine dose providing blood levels comparable or lower than the level provided by this product)
• Patients should not be tapered to a lower dose for the sole purpose of transitioning to this product.
• Stable transmucosal buprenorphine dose (of 8 mg/day or less of a Subutex sublingual tablet or Suboxone sublingual tablet or its transmucosal buprenorphine product equivalent) for at least 3 months without any need for supplemental dosing or adjustments
• The manufacturer product information should be consulted for examples of acceptable doses of transmucosal buprenorphine.

SUBLINGUAL TABLETS:

• After treatment induction and stabilization: 4 to 24 mg sublingually once a day
• Target dose: 16 mg sublingually once a day
• Maximum dose: 24 mg sublingually once a day
• Duration of maintenance therapy: No maximum is recommended.
• Indefinite treatment may be required and should continue for as long as the patient benefits and use of this product contributes to the intended treatment goals.
• If treatment goals are not being achieved: Reevaluate the appropriateness of continuing the current treatment.

Comments:

• This drug should be used as part of a complete treatment plan that includes counseling and psychosocial support.

SUBCUTANEOUS INJECTION:

• Due to the chronic nature of opioid use disorder, the need for continuing medication-assisted therapy should be reevaluated periodically.
• Brixadi:
• Patients currently being treated with a transmucosal buprenorphine-containing product may be switched directly to either the weekly or monthly formulation. Patients may be transitioned between weekly and monthly dosing based on clinical judgment.
• This product forms a biodegradable liquid crystalline gel upon injection that is not always palpable and may not be conducive to surgical removal; therefore, removal is not recommended.
• Sublocade:
• Patients should first undergo induction and stabilization by starting a buprenorphine-containing product (delivering the equivalent of 8 to 24 mg/day of transmucosal buprenorphine) for at least 7 days; dosing and induction with these products should be based on instructions in the appropriate manufacturer product information.
• For patients established on 100 mg/month: Allowance for a 2-month dosing interval may be appropriate on occasion (e.g., extended travel). In those cases, a single 300 mg dose may be given to cover a 2-month period; thereafter, the 100 mg/month regimen would resume.
• Patients should be cautioned that peak levels after a 300 mg injection will be higher than the usual monthly dose and sedation or other buprenorphine-related effects may occur.
• Patients established on long-term therapy with transmucosal buprenorphine (8 to 24 mg/day) and whose disease symptoms are controlled may be directly transitioned to this product.
• Potential differences in steady-state levels should be considered when transitioning a patient from long-term transmucosal buprenorphine therapy to this product.
• If the depot must be removed, it can be surgically excised under local anesthesia within 14 days of injection; only the most recently injected depot can be removed. Patients who have the depot removed should be monitored for signs/symptoms of withdrawal and treated appropriately.
• Residual plasma levels from previous injections will decrease gradually over subsequent months.

SUBDERMAL IMPLANT:

• This product is not appropriate for patients new to treatment and those who have not achieved and sustained prolonged clinical stability while being maintained on buprenorphine sublingual tablet 8 mg/day or less.
• The manufacturer product information should be consulted for factors to consider in determining clinical stability and suitability for this product.
• Implant insertions and removals should be performed by certified health care providers.
• Each dose consists of 4 implants; each implant contains 74.2 mg of buprenorphine.
• The insertion site should be examined 1 week after product insertion for signs of infection or any problems with wound healing (including evidence of implant extrusion from the skin); recommended visit schedule for most patients is no less often than once a month for continued counseling and psychosocial support.
• While some patients may require occasional supplemental dosing with buprenorphine, they should not be given prescriptions for transmucosal buprenorphine-containing products for as-needed use; patients who feel the need for supplemental dosing should be seen and evaluated promptly as ongoing use indicates the amount of drug delivered by this product is not adequate for stable maintenance.
• After 1 insertion in each arm, most patients should be transitioned back to a transmucosal product for continued treatment; there is no experience with inserting additional implants into other sites in the arm, into previously used administration sites, or into sites other than the upper arm.

SUBLINGUAL TABLETS:

• This product is preferred for induction; after induction, buprenorphine-naloxone sublingual film or tablets are preferred for maintenance therapy (due to the naloxone component), when clinical use includes unsupervised administration.
• The use of this product for unsupervised administration/maintenance should be limited to patients who cannot tolerate buprenorphine-naloxone sublingual film or tablets (e.g., known hypersensitivity to naloxone); the dosage should be progressively adjusted in increments/decrements of 2 to 4 mg to a level that keeps the patient in treatment and suppresses opioid withdrawal signs/symptoms.
• After treatment induction and stabilization, the maintenance dose generally ranges from 4 to 24 mg/day depending on the individual patient; dosages higher than 24 mg have not shown any clinical advantage.
• When determining prescription quantity for unsupervised administration, patient's level of stability, security of the home situation, and other factors likely to affect the ability to manage supplies of take-home medication should be considered.

Uses:

• Subcutaneous Injection:
• Brixadi: For the treatment of moderate to severe opioid use disorder in patients who have started treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine
• Sublocade: For the treatment of moderate to severe opioid use disorder in patients who have started treatment with a buprenorphine-containing product, followed by dose adjustment for at least 7 days
• Subdermal Implant: For the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low to moderate doses of a transmucosal buprenorphine-containing product (i.e., doses of no more than 8 mg/day of the sublingual tablet)
• Sublingual Tablets: For the treatment of opioid dependence

Usual Adult Dose for Pain

IM/IV INJECTION:
Initial dose: 0.3 mg IM or IV every 6 hours as needed

• Repeat up to 0.3 mg IM or IV once, if necessary, 30 to 60 minutes after initial dosage (considering previous dose pharmacokinetics [PKs]), and thereafter only as needed.
• Occasionally, single doses up to 0.6 mg IM may be necessary, depending on severity of pain and patient response; this dose should only be administered IM and only to patients who are not in a high-risk category.

Comments:

• Limitations of Use:
• Due to the risks of addiction, abuse, and misuse with opioids (which can occur at any dosage or duration), this product should be reserved for patients for whom alternative treatment options (e.g., nonopioid analgesics, opioid combination products): have not been tolerated or are not expected to be tolerated OR have not provided adequate analgesia or are not expected to provide adequate analgesia.
• This product should not be used for an extended duration unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.
• In high-risk patients (e.g., older adults, debilitated, presence of respiratory disease) and/or in patients where other CNS depressants are present (e.g., in the immediate postoperative period), the dose should be limited to the minimum required.
• Extra caution is recommended when using the IV route, especially with the initial dose.
• There are insufficient data to recommend single doses greater than 0.6 mg for long-term use.
• Many acute pain conditions (e.g., pain that occurs with numerous surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic; clinical guidelines on opioid prescribing for some acute pain conditions are available.
• The opioid analgesic dose and duration needed to adequately manage pain vary due to cause of pain and individual patient factors.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate

Usual Adult Dose for Chronic Pain

BUCCAL FILM:
Initial Dosing:
Opioid-naive or opioid-nontolerant patients: 75 mcg buccally once a day or, if tolerated, every 12 hours for at least 4 days, then increase to 150 mcg buccally every 12 hours
Titration: In increments of 150 mcg buccally every 12 hours, no more frequently than every 4 days

• In clinical trials, doses up to 450 mcg buccally every 12 hours were studied in opioid-naive patients.
• Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from other opioids: To reduce risk of opioid withdrawal, taper to no more than 30 mg/day oral morphine sulfate equivalents (MSE) before starting this product; after analgesic taper, base the starting dose on patient's daily opioid dose prior to taper as follows:

• For prior dose less than 30 mg/day oral MSE:
• Initial dose: 75 mcg buccally once a day or every 12 hours
• For prior dose 30 to 89 mg/day oral MSE:
• Initial dose: 150 mcg buccally every 12 hours
• For prior dose 90 to 160 mg/day oral MSE:
• Initial dose: 300 mcg buccally every 12 hours
• For prior dose greater than 160 mg/day oral MSE: Consider an alternate analgesic.

Titration: In increments of 150 mcg buccally every 12 hours, no more frequently than every 4 days

Titration and Maintenance Dosing:

• Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions.
• The minimum titration interval is 4 days (based on PK profile and time to reach steady-state plasma levels).
• Individual titration should proceed in increments of 150 mcg buccally every 12 hours.

Maximum Dose: 900 mcg buccally every 12 hours

• If pain is not adequately managed on 900 mcg: Consider an alternate analgesic.

TRANSDERMAL SYSTEM:
Initial Dosing:
Opioid-naive patients: Apply a 5 mcg/hour patch on intact skin.

• Each patch is intended to be worn for 7 days.

Conversion from other opioids:

• For prior total dose less than 30 mg/day oral MSE: Initiate therapy with a 5 mcg/hour patch at the next dosing interval.
• For prior total dose 30 to 80 mg/day oral MSE: Taper patient's current around-the-clock opioids for up to 7 days to no more than 30 mg/day MSE before starting therapy with this product; then initiate therapy with a 10 mcg/hour patch at the next dosing interval.
• For prior total dose greater than 80 mg/day oral MSE: A 20 mcg/hour patch may not provide adequate analgesia; consider use of an alternate analgesic.

Titration and Maintenance Dosing:

• Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions.
• The minimum titration interval is 72 hours (based on PK profile and time to reach steady-state levels).
• Dose adjustments may be made in 5, 7.5, or 10 mcg/hour increments by using no more than 2 patches of the 5, 7.5, or 10 mcg/hour system(s); total dose from both patches should not exceed 20 mcg/hour.

Maximum Dose: 20 mcg/hour

• In a clinical trial, 40 mcg/hour (given as 2 patches of the 20 mcg/hour system) resulted in QTc interval prolongation.

Comments:

• Limitations of Use:
• Due to the risks of addiction, abuse, and misuse with opioids (which can occur at any dosage or duration), and due to the greater risks of overdose and death with extended-release/long-acting opioid formulations, these products should be reserved for patients for whom alternative treatment options (e.g., nonopioid analgesics, immediate-release opioids) are ineffective, not tolerated, or would otherwise be inadequate to provide sufficient pain management.
• These products are not indicated as an as-needed analgesic.
• Individual titration to a dose that provides adequate analgesia and minimizes adverse reactions is recommended.
• Conversion from other opioids: When either product is started, all other opioid analgesics should be discontinued, except those used as needed for breakthrough pain when appropriate.
• There is a potential for this drug to precipitate withdrawal in patients already on opioids.
• Conversion from methadone: Regular evaluation is especially important 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.
• Patients should be continually reevaluated to assess the maintenance of pain control, signs/symptoms of opioid withdrawal, and other adverse reactions, as well as to reassess for development of addiction, abuse, or misuse.
• Frequent communication is important among the prescriber, other members of the health care team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.
• During extended therapy, the continued need for opioid analgesics should be periodically reassessed.
• Patients with breakthrough pain may need dosage adjustment of this product or rescue medication with an appropriate dose of an immediate-release analgesic.
• If pain level increases after dose stabilization, identifying the source of increased pain should be attempted before increasing the dose of this product; if unacceptable opioid-related adverse reactions occur (including increased pain after a dosage increase), reducing the dosage should be considered. The dosage should be adjusted to balance pain management and opioid-related adverse reactions.
• The maximum dose must not be exceeded due to the potential for QTc interval prolongation.

BUCCAL FILM:

• When switching from other opioids, patients may require additional short-acting analgesics during the taper period and during titration.
• This product may not provide adequate analgesia for patients requiring more than 160 mg/day oral MSE; use of an alternate analgesic should be considered.
• Due to interpatient variability in relative potency of opioid drugs and opioid formulations, a conservative approach is recommended when determining the total daily dosage of this product; 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 overdose.
• Doses of 600, 750, and 900 mcg are only for use after titration from lower doses of this product.

TRANSDERMAL SYSTEM:

• When switching from other opioids, patients may use short-acting analgesics as needed until analgesic efficacy with this product is attained.
• This product may not provide adequate analgesia for patients requiring more than 80 mg/day oral MSE; use of an alternate analgesic should be considered.
• Doses of 7.5, 10, 15, and 20 mcg/hour are only for use in patients who are opioid experienced and in whom tolerance to a comparably potent opioid has been established; opioid-experienced patients are patients receiving (for at least 1 week) opioid doses up to 80 mg/day oral MSE of another opioid.

Use: For the management of severe and persistent pain that requires an extended duration of therapy with a daily opioid analgesic and for which alternative treatment options are inadequate

Usual Pediatric Dose for Pain

IM/IV INJECTION:
2 to 12 years: 2 to 6 mcg/kg IM or IV every 4 to 6 hours

• Some patients may not need to be remedicated for 6 to 8 hours.

Over 12 years:

• Initial dose: 0.3 mg IM or IV every 6 hours as needed
• Repeat up to 0.3 mg IM or IV once, if necessary, 30 to 60 minutes after initial dosage (considering previous dose PKs), and thereafter only as needed.

Comments:

• Limitations of Use:
• Due to the risks of addiction, abuse, and misuse with opioids (which can occur at any dosage or duration), this product should be reserved for patients for whom alternative treatment options (e.g., nonopioid analgesics, opioid combination products) have not been tolerated or are not expected to be tolerated OR have not provided adequate analgesia or are not expected to provide adequate analgesia.
• This product should not be used for an extended duration unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.
• Patients aged 2 to 12 years: There is insufficient experience to recommend single doses greater than 6 mcg/kg or the use of a repeat/second dose at 30 to 60 minutes; because not all pediatric patients clear this drug faster than adults, fixed interval or around-the-clock dosing should not be used until the proper interdose interval has been established via clinical observation of the child.
• In high-risk patients (e.g., debilitated, presence of respiratory disease) and/or in patients where other CNS depressants are present (e.g., in the immediate postoperative period), the dose should be limited to the minimum required.
• Extra caution is recommended when using the IV route, especially with the initial dose.
• Many acute pain conditions (e.g., pain that occurs with numerous surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic; clinical guidelines on opioid prescribing for some acute pain conditions are available.
• The opioid analgesic dose and duration needed to adequately manage pain vary due to cause of pain and individual patient factors.

Use: For the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate

Usual Pediatric Dose for Opioid Use Disorder - Maintenance

SUBDERMAL IMPLANT:
16 years and older: Insert 1 dose subdermally in the inner side of the upper arm.

• This product is intended to be in place for 6 months; remove implants by the end of the sixth month.
• If continued treatment is desired at the end of the first 6-month treatment cycle:
• Insert new implants subdermally in the contralateral arm at time of removal.
• If new implants are not inserted on the same day as the removal, maintain patients on their previous dosage of transmucosal buprenorphine (i.e., the dose from which they were transferred) before additional treatment with this product.
• For patients who feel they need ongoing supplemental dosing with transmucosal buprenorphine: Consider alternate buprenorphine products for maintenance of treatment.

Patient Selection: This product is only for use in opioid-tolerant patients who meet ALL of the following criteria:

• Achieved and sustained prolonged clinical stability on transmucosal buprenorphine
• Currently on a maintenance dose of 8 mg/day or less of a buprenorphine (Subutex) or buprenorphine-naloxone (Suboxone) sublingual tablet or its transmucosal buprenorphine product equivalent (transmucosal buprenorphine dose providing blood levels comparable or lower than the level provided by this product)
• Patients should not be tapered to a lower dose for the sole purpose of transitioning to this product.
• Stable transmucosal buprenorphine dose (of 8 mg/day or less of a Subutex sublingual tablet or Suboxone sublingual tablet or its transmucosal buprenorphine product equivalent) for at least 3 months without any need for supplemental dosing or adjustments
• The manufacturer product information should be consulted for examples of acceptable doses of transmucosal buprenorphine.

Comments:

• This drug should be used as part of a complete treatment plan that includes counseling and psychosocial support.
• This product is not appropriate for patients new to treatment and those who have not achieved and sustained prolonged clinical stability while being maintained on buprenorphine sublingual tablet 8 mg/day or less.
• The manufacturer product information should be consulted for factors to consider in determining clinical stability and suitability for this product.
• Implant insertions and removals should be performed by certified health care providers.
• Each dose consists of 4 implants; each implant contains 74.2 mg of buprenorphine.
• The insertion site should be examined 1 week after product insertion for signs of infection or any problems with wound healing (including evidence of implant extrusion from the skin); recommended visit schedule for most patients is no less often than once a month for continued counseling and psychosocial support.
• While some patients may require occasional supplemental dosing with buprenorphine, they should not be given prescriptions for transmucosal buprenorphine-containing products for as-needed use; patients who feel the need for supplemental dosing should be seen and evaluated promptly as ongoing use indicates the amount of drug delivered by this product is not adequate for stable maintenance.
• After 1 insertion in each arm, most patients should be transitioned back to a transmucosal product for continued treatment; there is no experience with inserting additional implants into other sites in the arm, into previously used administration sites, or into sites other than the upper arm.

Use: For the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low to moderate doses of a transmucosal buprenorphine-containing product (i.e., doses of no more than 8 mg/day of the sublingual tablet)

Renal Dose Adjustments

Buccal Film, Subcutaneous Injection, Subdermal Implant, Sublingual Tablets, Transdermal System: Data not available

IM/IV Injection:

• Severe renal dysfunction: Caution recommended.

Comments:

• Buccal Film, IM/IV Injection: Because this drug is substantially excreted by the kidney, the risk of adverse reactions to this drug may be increased in patients with renal dysfunction.

Liver Dose Adjustments

Buccal Film:

• Severe liver dysfunction (Child-Pugh C): Reduce the starting dose and titration dose by half compared to normal liver function, from 150 mcg to 75 mcg.

IM/IV Injection:

• Severe liver dysfunction: Caution recommended.

Subcutaneous Injection, Subdermal Implant:

• Moderate to severe liver dysfunction: Not recommended
• If moderate to severe liver dysfunction develops during therapy:
• Brixadi: Dose adjustment may be required; however, no specific guidelines have been suggested. Caution recommended.
• Subdermal Implant: Removal of implants may be required.
• Sublocade: If signs/symptoms of toxicity or overdose occur within 2 weeks of administration, removal of the depot may be required.

Sublingual Tablets:

• Severe liver dysfunction: Consider reducing the starting dose and titration incremental dose by half.

Transdermal System:

• Severe liver dysfunction: Since this product is only intended for 7-day application, consider use of an alternate analgesic that may allow more flexibility with dosing.

Comments:

• Because this drug is metabolized by the liver, the activity may be increased and/or extended in patients with liver dysfunction.
• Buccal Film: Patients with moderate or severe liver dysfunction should be periodically assessed for signs/symptoms of toxicity or overdose caused by increased drug levels.
• Subcutaneous Injection, Subdermal Implant: Patients who develop moderate to severe liver dysfunction during therapy should be monitored for several months for signs/symptoms of toxicity or overdose caused by increased drug levels.
• Sublingual Tablets: Patients with severe liver dysfunction should be monitored for signs/symptoms of toxicity or overdose caused by increased drug levels.

Dose Adjustments

BUCCAL FILM:

• Patients with known/suspected oral mucositis: Reduce the starting dosage and titration incremental dosage by half compared to patients without mucositis.
• These patients should be regularly evaluated for signs/symptoms of toxicity or overdose caused by increased drug levels.

BUCCAL FILM, TRANSDERMAL SYSTEM:
Safe Reduction or Discontinuation of Therapy:

• This product should not be abruptly discontinued in patients who may be physically dependent on opioids.
• Rapid discontinuation of opioid analgesics in physically dependent patients has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.
• Rapid discontinuation has been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse; patients may attempt to treat their pain or withdrawal symptoms with illicit opioids (e.g., heroin) and other substances.
• When deciding to decrease the dose or discontinue therapy in an opioid-dependent patient, various factors should be considered, including the total daily opioid dose (including this product) the patient has been taking, the duration of therapy, the type of pain being treated, and the patient's physical and psychological attributes.
• 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 discontinuing opioid analgesics due to a suspected substance use disorder, the patient should be evaluated and treated, or referred for evaluation and treatment of the substance use disorder; treatment should include evidence-based approaches (e.g., medication assisted treatment of opioid use disorder); complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist.
• While there are no standard opioid tapering schedules suitable for all patients, good clinical practice dictates a patient-specific plan to taper the opioid dose gradually.
• For patients taking this product who are physically opioid-dependent, starting the taper in small increments (e.g., no greater than 10% to 25% of the total daily opioid dose) is recommended to avoid withdrawal symptoms, and dose-lowering should proceed at 2- to 4-week intervals.
• Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
• The patient may need to be given lower dosage strengths to accomplish a successful taper.
• The patient should be reassessed frequently to manage pain and withdrawal symptoms, should they emerge; common withdrawal symptoms (including restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis) and other signs/symptoms (including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure/respiratory rate/heart rate) may develop.
• If withdrawal symptoms occur, the taper may need to be paused for a period of time or the opioid analgesic dose may need to be increased to the prior dose, and then a slower taper should continue.
• Patients should be monitored for any changes in mood, emergence of suicidal thoughts, or use of other substances.
• When managing patients taking opioid analgesics (especially those treated for a long duration and/or with high doses for chronic pain), a multimodal approach to pain management (including mental health support, if needed) should be prepared before starting 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.

SUBCUTANEOUS INJECTION:
BRIXADI:

• An additional 8 mg injection of the weekly formulation may be administered (based on clinical judgment during a dosing interval) up to:
• Maximum dose of weekly formulation: 32 mg/week
• Maximum dose of monthly formulation: 128 mg/month

SUBLOCADE:

• For patients established on 100 mg/month: Allowance for a 2-month dosing interval may be appropriate on occasion (e.g., extended travel). In such cases, a single 300 mg dose may be given to cover a 2-month period; thereafter, the 100 mg/month regimen would resume.
• Patients should be cautioned that peak levels after a 300 mg injection will be higher than the usual monthly dose and sedation or other buprenorphine-related effects may occur.

Discontinuation of Therapy:

• If considering stopping therapy, the clinical status of the patient should be considered.
• If discontinued, the extended-release characteristics should be considered; the patient should be monitored for several months for signs/symptoms of withdrawal and treated appropriately.
• BRIXADI: After steady state has been achieved (4 weeks for the weekly formulation; 4 months for the monthly formulation), patients discontinuing this product may have detectable plasma levels of buprenorphine for about 1 month and about 4 months for the weekly and monthly formulations, respectively; the correlation between plasma drug levels and those detectable in urine is not known.
• SUBLOCADE: After steady state has been achieved (4 to 6 months), patients discontinuing this product may have detectable plasma and urine levels of buprenorphine for 12 months or longer.

SUBLINGUAL TABLETS:
Discontinuation of Therapy:

• The decision to discontinue therapy after a period of maintenance should be made as part of a comprehensive treatment plan.
• Patients should be apprised of the potential to relapse to illicit drug use after discontinuation of opioid agonist/partial agonist medication-assisted therapy.
• Patients should be tapered to reduce the occurrence of withdrawal signs/symptoms.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for buprenorphine:

• Brixadi: This REMS includes elements to assure safe use and an implementation system.
• Buprenorphine Transmucosal Products for Opioid Dependence: This shared system REMS includes a medication guide, elements to assure safe use, and an implementation system.
• This does not apply to buprenorphine-containing products that are dispensed to patients undergoing treatment through an Opioid Treatment Program under Part 8 of Title 42 of the Code of Federal Regulations.
• Opioid Analgesic REMS: This shared system REMS includes a medication guide and elements to assure safe use.
• This includes all opioid analgesics used in the outpatient setting and not covered by other REMS programs.
• Probuphine: This REMS includes a medication guide, elements to assure safe use, and an implementation system.
• Sublocade: This REMS includes elements to assure safe use and an implementation system.

For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS (BUCCAL FILM, IM/IV INJECTION, TRANSDERMAL SYSTEM):

• ADDICTION, ABUSE, AND MISUSE: Because use of this product exposes patients and other users to the risks of opioid addiction, abuse, and misuse (which can lead to overdose and death), each patient's risk should be assessed before prescribing; all patients should be reassessed regularly for development of such behaviors and conditions.
• LIFE-THREATENING RESPIRATORY DEPRESSION: Serious, life-threatening, or fatal respiratory depression may occur with use of this product (especially during initiation or after dosage increase); proper dosing and titration are essential to reduce the risk of respiratory depression.
• Misuse or abuse of this product by chewing, swallowing, snorting, or injecting buprenorphine extracted from the BUCCAL FILM or TRANSDERMAL SYSTEM will result in uncontrolled drug delivery and pose a significant risk of overdose and death.
• RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS: Concomitant use of opioids with benzodiazepines or other CNS depressants (including alcohol) may cause profound sedation, respiratory depression, coma, and death. Concomitant prescribing of this product and benzodiazepines or other CNS depressants should be reserved for patients whose alternative treatment options are inadequate.
• NEONATAL OPIOID WITHDRAWAL SYNDROME (NOWS): If opioid use is needed for an extended duration in a pregnant woman, the patient should be apprised of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery.

US BOXED WARNINGS (BUCCAL FILM, TRANSDERMAL SYSTEM):

• ACCIDENTAL EXPOSURE: Accidental exposure of even 1 dose of this product (especially in children) can result in a fatal overdose.
• OPIOID ANALGESIC REMS: Health care providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription.

US BOXED WARNINGS (SUBCUTANEOUS INJECTION):

• RISK OF SERIOUS HARM OR DEATH WITH IV ADMINISTRATION: Serious harm or death could result if administered IV. Brixadi and Sublocade form a liquid crystalline gel and solid mass, respectively, upon contact with body fluids; these products may cause occlusion, local tissue damage, and thromboembolic events (including life-threatening pulmonary emboli) if administered IV.
• BRIXADI REMS/SUBLOCADE REMS: Due to the risk of serious harm or death that could occur from IV self-administration, this product is only available through a restricted program. Health care settings and pharmacies that order and dispense this product must be certified in the program and comply with the REMS requirements.

US BOXED WARNING (SUBDERMAL IMPLANT):

• IMPLANT MIGRATION, PROTRUSION, EXPULSION, AND NERVE DAMAGE ASSOCIATED WITH INSERTION AND REMOVAL: Insertion and removal of this product are associated with the risk of implant migration, protrusion, and expulsion resulting from the procedure. Rare but serious complications (including nerve damage and migration leading to embolism and death) may result from improper insertion of drug implants inserted in the upper arm; additional complications may include local migration, protrusion, and expulsion. Protrusion or expulsion may occur due to incomplete insertions or infections. Because of the risks associated with insertion and removal, this product is available only through a restricted program. All health care providers must successfully complete a live training program on the insertion and removal procedures and become certified, before performing insertions or prescribing this product; patients must be monitored to ensure that the implant is removed by a health care provider certified to perform insertions.

CONTRAINDICATIONS:
For Opioid Dependence:

• Hypersensitivity (e.g., anaphylactic shock)/history of hypersensitivity to the active component or any of the ingredients

For Pain:

• Significant respiratory depression
• Acute of severe bronchial asthma in an unmonitored setting or without resuscitative equipment
• Known/suspected gastrointestinal obstruction (including paralytic ileus)
• Hypersensitivity (e.g., anaphylaxis) to the active component or any of the ingredients

Buccal Film, Subcutaneous Injection, Sublingual Tablets, Transdermal System: Safety and efficacy have not been established in patients younger than 18 years.
IM/IV Injection: Safety and efficacy have not been established in patients younger than 2 years.
Subdermal Implant: Safety and efficacy have not been established in patients younger than 16 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule III

Dialysis

Data not available

Other Comments

Administration advice:
FOR OPIOID DEPENDENCE:
Subcutaneous Injection:

• For subcutaneous injection only; do not administer IV, IM, or intradermally.
• Only health care providers should administer this product.
• Initiating therapy with this product as the first buprenorphine product has not been studied.
• Administer each injection using only the syringe and safety needle included with the product.
• Brixadi:
• This product exists in 2 formulations; doses of the weekly formulation cannot be combined to yield a monthly dose.
• Administer this product as a single injection; do not divide.
• Inject slowly into the subcutaneous tissue of the buttock, thigh, abdomen, or upper arm.
• In patients not currently receiving buprenorphine: For the weekly formulation, use the upper arm site only after steady state has been reached (4 consecutive doses); injection in the arm site was associated with about 10% lower plasma levels than other sites.
• Do not administer the weekly formulation to the same site of injection for at least 8 weeks; no injection site rotation is needed for the monthly formulation.
• For all patients, individualize the dose based on patient tolerability and/or efficacy.
• Administer the weekly formulation in 7-day intervals.
• Administer the monthly formulation in 28-day intervals.
• For patients not currently receiving buprenorphine: Begin with a test dose of 4 mg transmucosal buprenorphine to establish that this drug is tolerated without precipitated withdrawal, and then transition to the weekly formulation.
• Initiating treatment with the monthly formulation in patients new to therapy has not been studied.
• In patients currently being treated with other buprenorphine-containing products: Start therapy with either the weekly or monthly formulation.
• To avoid missed doses, the weekly dose may be administered up to 2 days before or after the weekly time point, and the monthly dose may be administered up to 1 week before or after the monthly time point; if a dose is missed, administer the next dose as soon as possible.
• Sublocade:
• Start this product only after induction and dose adjustment with a transmucosal buprenorphine-containing product.
• For abdominal subcutaneous injection only
• Choose an injection site on the abdomen between the transpyloric and transtubercular planes with adequate subcutaneous tissue free of skin conditions (e.g., nodules, lesions, excessive pigment); the patient should be in the supine position.
• Do not inject into an area where the skin is irritated, reddened, bruised, infected, or scarred in any way.
• Administer monthly with at least 26 days between doses.
• To avoid irritation, rotate injection sites; record the injection location to ensure a different site is used at the time of the next injection.
• If a dose is missed, administer the next dose as soon as possible, with the following dose administered no less than 26 days later; occasional delays in dosing up to 2 weeks are not expected to have a clinically significant impact on treatment effect.

Subdermal Implant:

• Implants must be inserted and removed by certified health care providers.
• Before inserting this product, carefully read the insertion instructions as well as the full manufacturer product information.
• Insert subdermally in the inner side of the upper arm.
• Before starting the removal procedure, read the instructions for removal.
• If spontaneous expulsion occurs, follow the steps provided in the manufacturer product information.
• For additional information: probuphinerems.com or 1-844-859-6341

Sublingual Tablets:

• Consider the frequency of visits when prescribing this product; providing multiple refills is not recommended early in therapy or without appropriate patient follow-up visits.
• Administer sublingually as a single daily dose.
• Administer tablets whole; do not cut, chew, or swallow sublingual tablets.
• Do not eat or drink anything until the tablet is completely dissolved.
• Place tablet under the tongue until it is dissolved.
• For doses requiring the use of more than 2 tablets, either place all the tablets at once or alternatively (if more than 2 tablets cannot fit comfortably), place 2 tablets at a time under the tongue; either way, continue to hold the tablets under the tongue until they dissolve (swallowing the tablets reduces drug bioavailability).
• To ensure consistency in bioavailability, follow the same manner of dosing with continued use of the product.
• Demonstrate proper administration technique to the patient.
• After the product has completely dissolved in the oral mucosa, take a sip of water, swish gently around the teeth and gums, and swallow; wait for at least 1 hour after taking this product before brushing teeth.
• Initiate treatment with supervised administration, and progress to unsupervised administration as the patient's clinical stability permits; use of this product for unsupervised administration should be limited to patients who cannot tolerate buprenorphine-naloxone.
• If a dose is missed, take it as soon as remembered; if it is almost time for the next dose, skip the missed dose and take the next dose at the regular time.

FOR PAIN:

• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals; because the risk of overdose increases as opioid doses increase, reserve titration to higher doses for patients in whom lower doses are insufficient and the expected benefits clearly outweigh the substantial risks.
• Initiate the dosing regimen for each patient individually, considering the patient's underlying cause and severity of pain, prior analgesic therapy and response, and risk factors for addiction, abuse, and misuse.
• Respiratory depression can occur at any time during opioid therapy, especially when starting and after dosage increases; consider this risk when selecting an initial dose and making dose adjustments.

Buccal Film:

• For oral buccal use only; apply to the buccal mucosa every 12 hours.
• Do not use if the pouch seal is broken or if the film is cut, damaged, or changed in any way; avoid applying to areas of the mouth with any open sores or lesions.
• First, use the tongue to wet the inside of the cheek or rinse the mouth with water to wet the area for placement of this product; then apply the film immediately after removal from the individually sealed package. Place the yellow side of the film against the inside of the cheek; hold the entire film in place with clean, dry fingers for 5 seconds, then leave in place on the inside of the cheek until fully dissolved.
• This product adheres to the moist buccal mucosa and will completely dissolve after application (usually within 30 minutes); do not manipulate the film with the tongue or finger(s) and avoid eating food and drinking liquids until the film has dissolved.
• After the product has completely dissolved in the oral mucosa, take a sip of water, swish gently around the teeth and gums, and swallow; wait for at least 1 hour after taking this product before brushing teeth.
• If the film is chewed or swallowed, Cmax and bioavailability may be lower than when used as directed.
• Demonstrate proper administration technique to the patient.

IM/IV Injection:

• Administer by deep IM or slow (over at least 2 minutes) IV injection; exercise extra care with the IV route of administration (especially with the initial dose).

Transdermal System:

• For transdermal use (on intact skin) only; each patch is intended to be worn for 7 days.
• Apply immediately after removal from the individually sealed pouch.
• Do not use if the pouch seal is broken or the patch is cut, damaged, or changed in any way; do not cut this product.
• Consult the Instructions for Use for step-by-step instructions for applying this product.
• Apply patch to the upper outer arm, upper chest, upper back, or side of the chest; these 4 sites (each present on both sides of the body) provide 8 possible application sites. Rotate among the 8 described skin sites; after removal, wait at least 21 days before reapplying to the same skin site.
• For the use of 2 patches: Remove current patch and apply the 2 new patches at the same time, adjacent to 1 another at a different application site.
• Apply patch to a hairless/nearly hairless skin site; if none are available, clip the hair at the site (do not shave). Do not apply to irritated skin.
• If the application site must be cleaned, clean with water only; do not use soaps, alcohol, oils, lotions, or abrasive devices. Allow the skin to dry before applying this product.
• Incidental exposure of the patch to water (such as while bathing/showering) is acceptable based on experience during clinical studies.
• If problems with adhesion of the patch occur, the edges may be taped with first aid tape; if problems with lack of adhesion continue, the patch may be covered with waterproof/semipermeable adhesive dressings suitable for 7 days of wear.
• If the patch falls off during the 7-day dosing interval, dispose of it properly and apply a new patch to a different skin site.
• When changing the system, remove the product and dispose of it properly.
• Avoid exposing this product to external heat sources, hot water, or prolonged direct sunlight.

Storage requirements:

• Most products: Store at 20C to 25C (68C to 77F); excursions permitted to 15C to 30C (59F to 86F). Store securely and dispose of properly.
• IM/IV Injection: Protect from prolonged exposure to light.
• Sublocade (subcutaneous injection): Store refrigerated at 2C to 8C (35.6F to 46.4F); once outside the refrigerator, may store in original packaging at room temperature (15C to 30C [59F to 86F]) for up to 12 weeks prior to administration
• Remove from the refrigerator before administration; the product requires at least 15 minutes to reach room temperature.
• Discard if left at room temperature for longer than 12 weeks.

Reconstitution/preparation techniques:

• Subcutaneous Injection: Only health care providers should prepare this product.
• Sublocade: Do not open the foil pouch until the patient has arrived for the injection; do not attach the needle until time of administration.
• The manufacturer product information should be consulted.

General:

• This drug is a potent opioid and has been associated with abuse and dependence among health care providers; to control risk of diversion, measures appropriate to the health care setting should be taken to provide rigid accounting, control of wastage, and restriction of access.

For Opioid Dependence:

• Subcutaneous Injection:
• Periodic assessment is needed to determine efficacy of the treatment plan and overall patient progress; when evaluating the patient, the injection site should be examined for signs of infection or evidence of tampering/attempts to remove the depot.
• Brixadi: The needle cap is synthetically derived from natural rubber latex which may cause allergic reactions in latex-sensitive individuals.
• Sublocade: If the depot is removed, it should be handled with adequate security, accountability, and proper disposal.
• Sublingual Tablets:
• Ideally, patients should be seen at reasonable intervals (e.g., at least weekly during the first month of therapy) based on the patient's individual circumstances; periodic assessment is needed to determine compliance with the dosing regimen, efficacy of the treatment plan, and overall patient progress.
• Once a stable dosage has been achieved and patient assessment (e.g., urine drug screening) does not indicate illicit drug use, less frequent follow-up visits may be appropriate; continuation or modification of pharmacotherapy should be based on the health care provider's evaluation of treatment outcomes and objectives (the manufacturer product information should be consulted).
• Health care providers will need to decide when they cannot appropriately provide further management for particular patients; in such cases, the health care provider may want to assess whether to refer the patient to a specialist or more intensive behavioral treatment environment. Decisions should be based on the treatment plan established and agreed upon with the patient at the start of therapy.
• Patients who continue to misuse, abuse, or divert this drug or other opioids should be provided with, or referred to, more intensive and structured therapy.

For Pain:

• Buccal Film, IM/IV Injection, Transdermal System: These products should be prescribed only by health care professionals knowledgeable about the use of opioids (IM/IV Injection) or extended-release/long-acting opioids (Buccal Film, Transdermal System) and how to mitigate associated risks.
• IM/IV Injection:
• Accidental dermal exposure should be treated by removal of contaminated clothing and rinsing the affected area with water.
• This product should be administered with caution in older adult patients, debilitated patients, children, and those with severe pulmonary dysfunction, myxedema/hypothyroidism, adrenal cortical insufficiency (e.g., Addison's disease), CNS depression/coma, toxic psychoses, prostatic hypertrophy/urethral stricture, acute alcoholism, delirium tremens, or kyphoscoliosis.
• Transdermal System:
• If the buprenorphine-containing adhesive matrix accidentally contacts the skin, patients or caregivers should be instructed to wash the area with water and not to use soap, alcohol, or other solvents to remove the adhesive because they may enhance drug absorption.
• Disposal Instructions: Patients should consult the Instructions for Use for proper disposal; used and unused patches should be disposed of by following the instructions on the Patch-Disposal Unit that is packaged with the product.
• 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.

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose (Buccal Film, Subcutaneous Injection, Subdermal Implant, Sublingual Tablets, Transdermal System):

• The availability of naloxone for the emergency treatment of opioid overdose should be discussed with the patient and caregiver. Both when starting and renewing treatment:
• For opioid dependence: Strongly consider prescribing naloxone for the emergency treatment of opioid overdose; patients being treated for opioid use disorder have the potential for relapse, which places them at risk for opioid overdose. Patients and caregivers should be advised that naloxone may also be administered for a known/suspected overdose with buprenorphine itself; higher than normal doses and repeated administration of naloxone may be required due to the long duration of action of buprenorphine and its affinity for the mu receptor.
• For pain: Assess the potential need for access to naloxone. Prescribing naloxone should be considered based on patient risk factors for overdose (e.g., concomitant use of CNS depressants, history of opioid use disorder, prior opioid overdose); however, presence of risk factors for overdose should not prevent proper pain management in any given patient.
• Prescribing naloxone should be considered if the patient has household members (including children) or other close contacts at risk for accidental ingestion/exposure or overdose.
• Patients and caregivers should be informed about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements/guidelines (e.g., by prescription, directly from pharmacist, as part of community-based program).

Monitoring:

• Cardiovascular: For signs of hypotension (when starting or titrating dosage)
• Gastrointestinal: For worsening symptoms in patients with biliary tract disease, including acute pancreatitis
• Hepatic: Liver enzyme levels in patients at increased risk of hepatotoxicity (at baseline and periodically during therapy)
• Nervous System: For signs/symptoms of sedation (especially at start of therapy); for worsened seizure control in patients with history of seizure disorders (during therapy)
• Psychiatric: For development of opioid addiction, abuse, or misuse in all patients (during therapy)
• Respiratory: For signs/symptoms of respiratory depression (especially at start of therapy and when titrating dosage)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide [buccal film, subcutaneous injection, subdermal implant, sublingual tablets]; Medication Guide and Instructions for Use [transdermal system]).
• Read the Medication Guide each time this drug is dispensed, administered, or implanted because new information may be available.
• If naloxone is prescribed: Tell family and friends about your naloxone and keep it in a place where they can access it in an emergency. Read the Patient Information (or other educational material) that comes with naloxone; it is important to do this before an opioid emergency happens so you and your caregiver will know what to do.
• Seek medical attention immediately if symptoms of serotonin syndrome develop after hospital discharge; inform health care providers if you are taking (or plan to take) serotonergic medications.
• This drug may impair mental or physical abilities needed to perform potentially hazardous activities (e.g., driving a vehicle, operating machinery).
• Buccal film, IM/IV injection, transdermal system: Do not drive or operate dangerous machinery unless you are tolerant to the effects of this drug and/or know how you will react to the medication.
• Subcutaneous injection, subdermal implant: Do not drive or operate dangerous machinery until you are reasonably certain that this drug does not adversely affect your ability to engage in such activities.
• Sublingual tablets: Use caution (especially during drug induction and dose adjustment) until you are reasonably certain that this drug does not adversely affect your ability to engage in such activities.

Buccal Film, Subcutaneous Injection, Subdermal Implant, Sublingual Tablets, Transdermal System:

• Call 911 or get emergency medical aid immediately in all cases of a known/suspected overdose, even if naloxone is administered.
• Do not use this product with benzodiazepines or other CNS depressants (including alcohol) unless supervised by a health care provider.
• Seek medical attention if signs/symptoms of adrenal insufficiency (e.g., nausea, vomiting, anorexia, fatigue, weakness, dizziness, low blood pressure) develop.

Buccal Film, Sublingual Tablets, Transdermal System:

• Store this product securely, out of sight and reach of children, and in a location not accessible by others (including visitors to the home); leaving this drug unsecured can present a deadly risk to others in the home.
• Do not share with others; take steps to protect this product from theft or misuse.

Buccal Film, Sublingual Tablets:

• When no longer needed, dispose of this product promptly per Medication Guide.
• You should have regular dental checkups while taking this product; inform your dentist that you have started this product.

Buccal Film, Transdermal System:

• Do not increase opioid dosages without first consulting a clinician; seek medical attention if symptoms of hyperalgesia (including worsening pain, increased sensitivity to pain, or new pain) develops.
• To avoid developing withdrawal symptoms, do not discontinue this product without first discussing a tapering plan with the prescriber.
• Patients of childbearing potential: Inform your health care provider of a known/suspected pregnancy.
• Do not breastfeed during therapy.

IM/IV Injection: Inform health care provider if hyperalgesia (including worsening pain, increased sensitivity to pain, or new pain) develops.

Subcutaneous Injection, Subdermal Implant, Sublingual Tablets: Inform your family members to, in case of an emergency, inform the treating health care provider or emergency room staff that you are physically dependent on an opioid and are being treated with this product.

Subcutaneous Injection:

• Seek emergency attention if signs/symptoms of respiratory depression, CNS depression, or overdose occur.
• Do not tamper with or try to remove your depot.

Subdermal Implant:

• Contact a health care provider immediately if any of the following occur: the implant protrudes or is expelled; bleeding or symptoms of infection (e.g., excessive/worsening itching, pain, irritation/redness, swelling at insertion site); symptoms suggesting the implant has migrated (e.g., numbness/weakness, shortness of breath); symptoms of numbness/weakness in the arm after insertion or removal procedure.
• If the implants protrude or are expelled, you should: wash your hands if you touched the implants; cover the area where the implants were inserted with a clean bandage; not allow others to touch or use the implants as this could be very dangerous; place the implants in a plastic bag and take to a health care provider immediately; keep the implants away from others (especially children); protect the implants from theft until you can take them to your doctor.

Sublingual Tablets:

• Seek immediate medical attention if a child is exposed to this product.
• Do not change the dosage without consulting your health care providers.
• If seeking to discontinue therapy, work closely with your health care providers on a tapering schedule.

Transdermal System: When no longer needed, dispose of this product promptly per Medication Guide and Instructions for Use.

Frequently asked questions

• How long does opioid withdrawal last?
• How long does buprenorphine stay in your system?
• What are the different brands of buprenorphine?
• What is the difference between Sublocade and Brixadi?
• What are the different types of buprenorphine/naloxone?
• How long do you take buprenorphine for?
• Is Buprenex the same as buprenorphine?

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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