buprenorphine/naloxone (Rx)

Brand and Other Names:Suboxone, Zubsolv, more...Bunavail, Cassipa
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

buprenorphine/naloxone

film, sublingual: Schedule III

  • 2mg/0.5mg (Suboxone, generic)
  • 4mg/1mg (Suboxone, generic)
  • 8mg/2mg (Suboxone, generic)
  • 12mg/3mg (Suboxone, generic)
  • 16mg/4mg (Cassipa)

tablet, sublingual (Zubsolv): Schedule III

  • 0.7mg/0.18mg
  • 1.4mg/0.36mg
  • 2.9mg/0.71mg
  • 5.7mg/1.4mg
  • 8.6mg/2.1mg
  • 11.4mg/2.9mg

buccal film (Bunavail): Schedule III

  • 2.1mg/0.3mg
  • 4.2mg/0.7mg
  • 6.3mg/1mg

tablet, sublingual (generic): Schedule III

  • 2mg/0.5mg
  • 8mg/2mg

Opioid Dependence

Induction (buprenorphine SL)

  • Day 1: 4 mg SL initially; may be repeated after 2 hours if withdrawal symptoms are not relieved; not to exceed 8 mg
  • Day 2: If no withdrawal symptoms are present, 4 mg SL; if withdrawal symptoms are present, dose is increased by 4 mg; if symptoms are not relieved after >2 hr, 4 mg is administered; not to exceed 16 mg SL
  • Switch to buprenorphine/naloxone for unsupervised maintenance

Induction (buprenorphine/naloxone [Suboxone])

  • Caution: buprenorphine/naloxone (Suboxone) induction is only for patients dependent on short-acting opioids (eg, heroin) and not for those dependent on long-acting opioids (eg, methadone); buprenorphine monotherapy is recommended for induction for long-acting opioids
  • Day 1: 2 mg/0.5 mg or 4 mg/1 mg SL initially; may titrate upwards in 2-4 mg increments at 2 hr intervals, under supervision; not to exceed 8 mg/2 mg
  • Day 2: Up to 16 mg/4 mg SL as a single daily dose

Induction (buprenorphine/naloxone [Zubsolv])

  • Caution: buprenorphine/naloxone (Zubsolv) induction is only for patients dependent on short-acting opioids (eg, heroin) and not for those dependent on long-acting opioids (eg, methadone); buprenorphine monotherapy is recommended for induction for long-acting opioids
  • Day 1
    • An induction dose of up to 5.7 mg/1.4 mg is recommended, given in divided doses; initiate with 1.4 mg/0.36 mg SL; give remainder of Day 1 dose of up to 4.2 mg/1.08 mg should be divided into doses of 1 to 2 tablets of 1.4 mg/0.36 mg at 1.5 to 2 hr intervals
    • Some patients (eg, those with recent exposure to buprenorphine) may tolerate up to 3 x 1.4 mg/0.36 mg SL as a single, second dose
  • Day 2
    • A single daily dose up to 11.4 mg/2.9 mg SL is recommended

Induction (buprenorphine/naloxone [Bunavail])

  • Caution: buprenorphine/naloxone (Bunavail) induction is only for patients dependent on short-acting opioids (eg, heroin) and not for those dependent on long-acting opioids (eg, methadone); buprenorphine monotherapy is recommended for induction for long-acting opioids
  • Day 1
    • The first dose should not be administered <6 hr after the patient last used an opioid
    • An induction dose of up to 4.2 mg/0.7 mg is recommended; initiate with 2.1 mg/0.3 mg and repeat at ~2-hr, under supervision, to a total dose of 4.2 mg/0.7 mg based on control of acute withdrawal symptoms
  • Day 2
    • A single daily dose up to 8.4 mg/1.4 mg buccal is recommended

Maintenance

  • Suboxone
    • Target dose: 12-16 mg/4 mg buprenorphine/naloxone SL as a single daily dose
    • Range: 16-24 mg buprenorphine component; not to exceed 32 mg/day
    • Progressively adjust buprenorphine/naloxone dose in increments or decrements of 2 mg/0.5 mg or 4 mg/1 mg to level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
  • Zubsolv
    • Target dose: 11.4/2.9 mg as a single daily dose
    • Range: 2.9/0.71 mg to 17.2/4.2 mg
    • Progressively adjust buprenorphine/naloxone dose in increments or decrements of 1.4/0.36 mg or 2.9/0.71 mg to level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
  • Bunavail
    • Target dose: 8.4/1.4 mg as a single daily dose
    • Range: 2.1/0.3 mg to 12.6/2.1 mg
    • Progressively adjust dose in increments or decrements of 2.1/0.3 mg to a level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
    • There is no maximum recommended duration of maintenance treatment; for some patients, treatment may continue indefinitely
  • Cassipa
    • Used after induction and stabilization of the patient, and after buprenorphine dose titrated to 16 mg using another marketed product
    • If dose needs adjustment in order to maintain treatment and suppress opioid withdrawal signs and symptoms, a different product will be needed; Cassipa comes in a single dose and cannot be adjusted (ie, SL film available only as 16 mg buprenorphine/4 mg naloxone)
    • There is no maximum recommended duration of maintenance treatment; for some patients, treatment may continue indefinitely

Dosage Modifications

Hepatic impairment

  • Mild: No dosage adjustment necessary
  • Moderate: May not be appropriate
  • Severe: Avoid use

Renal impairment

  • No differences in buprenorphine pharmacokinetics observed between 9 dialysis-dependent and 6 normal patients following IV administration of 0.3 mg buprenorphine
  • Renal failure: Unknown

Dosing Considerations

Prior to induction, consideration should be given to the type of opioid dependence (ie, long- or short-acting opioid products, the time since last opioid use, and the degree or level of opioid dependence

To avoid precipitating an opioid withdrawal syndrome, the first dose of buprenorphine/naloxone should be administered only when objective and clear signs of moderate withdrawal are evident, and divided doses should be used

It is recommended that an adequate treatment dose, titrated to clinical effectiveness, be achieved as rapidly as possible

Patients dependent on methadone or long-acting opioid products may be more susceptible to precipitated and prolonged withdrawal during induction than those on short-acting opioid products; buprenorphine monotherapy is recommended in patients taking long-acting opioids instead of buprenorphine/naloxone, which may worsen withdrawal symptoms

Patients dependent on heroin or other short-acting opioid products may be induced with buprenorphine/naloxone or with SL buprenorphine monotherapy

Equivalents

  • Zubsolv 5.7/1.4 mg SL provides equivalent buprenorphine exposure to Suboxone 8/2 mg SL
  • Bunavail 2.1/0.3 mg buccal provides equivalent buprenorphine exposure to Suboxone 4/1 mg SL
  • Bunavail 4.2/0.7 mg buccal provides equivalent buprenorphine exposure to Suboxone 8/2 mg SL
  • Bunavail 6.3/1 mg buccal provides equivalent buprenorphine exposure to Suboxone 12/3 mg SL

Access to naloxone for opioid overdose

  • Assess need for naloxone upon initiating and renewing treatment
  • Consider prescribing naloxone
    • Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
    • Household members (including children) or other close contacts at risk for accidental ingestion or overdose
  • Consult patients and caregivers on the following:
    • Availability of naloxone for emergency treatment of opioid overdose
    • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)

Safety and efficacy not established

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Interactions

Interaction Checker

and buprenorphine/naloxone

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            Contraindicated (2)

            • alvimopan

              alvimopan, buprenorphine. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

            • lefamulin

              lefamulin will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.

            Serious - Use Alternative (46)

            • abametapir

              abametapir will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use is warranted, carefully monitor, particularly during treatment initiation and dose adjustment. Discontinue oliceridine if serotonin syndrome is suspected.

            • alfentanil

              buprenorphine, alfentanil. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • apalutamide

              apalutamide will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • belladonna and opium

              buprenorphine, belladonna and opium. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              buprenorphine decreases effects of benzhydrocodone/acetaminophen by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone (benzhydrocodone prodrug of hydrocodone) and/or precipitate withdrawal symptoms in opioid tolerant patients.

            • bremelanotide

              bremelanotide will decrease the level or effect of buprenorphine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

            • butorphanol

              buprenorphine, butorphanol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • calcium/magnesium/potassium/sodium oxybates

              buprenorphine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • chloramphenicol

              chloramphenicol will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cimetidine

              cimetidine increases effects of buprenorphine by decreasing metabolism. Avoid or Use Alternate Drug.

            • clarithromycin

              clarithromycin will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clonidine

              clonidine, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

            • codeine

              buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • conivaptan

              conivaptan will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • dextromoramide

              buprenorphine, dextromoramide. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • diamorphine

              buprenorphine, diamorphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • diazepam intranasal

              diazepam intranasal, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • difenoxin hcl

              buprenorphine, difenoxin hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • diphenoxylate hcl

              buprenorphine, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • dipipanone

              buprenorphine, dipipanone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • eluxadoline

              buprenorphine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

            • fentanyl

              fentanyl, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

              buprenorphine decreases effects of fentanyl by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.

            • fentanyl intranasal

              fentanyl intranasal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

              buprenorphine decreases effects of fentanyl intranasal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.

            • fentanyl transdermal

              fentanyl transdermal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

              buprenorphine decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.

            • fentanyl transmucosal

              fentanyl transmucosal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

              buprenorphine decreases effects of fentanyl transmucosal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.

            • fexinidazole

              fexinidazole and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels and/or prolong QT interval.

              fexinidazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • hydrocodone

              buprenorphine decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .

              hydrocodone, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • hydromorphone

              buprenorphine, hydromorphone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • idelalisib

              idelalisib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • isocarboxazid

              isocarboxazid increases toxicity of buprenorphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • itraconazole

              itraconazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketoconazole

              ketoconazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • levorphanol

              buprenorphine, levorphanol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • linezolid

              linezolid increases toxicity of buprenorphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • lonafarnib

              lonafarnib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • meperidine

              buprenorphine, meperidine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • methadone

              buprenorphine, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • methylene blue

              methylene blue and buprenorphine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

            • metoclopramide intranasal

              buprenorphine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • mifepristone

              mifepristone will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • morphine

              buprenorphine, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • nalbuphine

              buprenorphine, nalbuphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • naldemedine

              naldemedine, naloxone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive opioid receptor anatagonism and increased risk of opioid withdrawal.

            • naloxegol

              naloxegol, naloxone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration; potential for additive effect of opioid receptor anatagonism and increased risk of opioid withdrawal.

            • nefazodone

              nefazodone will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (207)

            • albuterol

              buprenorphine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alfentanil

              alfentanil and buprenorphine both increase sedation. Use Caution/Monitor.

            • alprazolam

              alprazolam and buprenorphine both increase sedation. Use Caution/Monitor.

            • amitriptyline

              buprenorphine and amitriptyline both increase sedation. Use Caution/Monitor.

            • amobarbital

              amobarbital and buprenorphine both increase sedation. Use Caution/Monitor.

              amobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • amoxapine

              buprenorphine and amoxapine both increase sedation. Use Caution/Monitor.

            • apalutamide

              apalutamide will decrease the level or effect of buprenorphine by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.

            • apomorphine

              buprenorphine and apomorphine both increase sedation. Use Caution/Monitor.

            • aripiprazole

              buprenorphine and aripiprazole both increase sedation. Use Caution/Monitor.

            • armodafinil

              buprenorphine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atazanavir

              atazanavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity.

            • azelastine

              azelastine and buprenorphine both increase sedation. Use Caution/Monitor.

            • baclofen

              baclofen and buprenorphine both increase sedation. Use Caution/Monitor.

            • belladonna and opium

              buprenorphine and belladonna and opium both increase sedation. Use Caution/Monitor.

            • benperidol

              buprenorphine and benperidol both increase sedation. Use Caution/Monitor.

            • benzphetamine

              buprenorphine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • bosentan

              bosentan will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexanolone

              brexanolone, buprenorphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brompheniramine

              brompheniramine and buprenorphine both increase sedation. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              buprenorphine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants 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.

            • butabarbital

              butabarbital and buprenorphine both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital and buprenorphine both increase sedation. Use Caution/Monitor.

            • butorphanol

              buprenorphine and butorphanol both increase sedation. Use Caution/Monitor.

            • carbamazepine

              carbamazepine decreases levels of buprenorphine by increasing metabolism. Use Caution/Monitor. Carbamazepine increases metabolism of buprenorphine; monitor for decreased efficacy.

              carbamazepine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine and buprenorphine both increase sedation. Use Caution/Monitor.

            • carisoprodol

              carisoprodol and buprenorphine both increase sedation. Use Caution/Monitor.

            • cenobamate

              cenobamate will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

              cenobamate, buprenorphine. Either increases effects of the other by sedation. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate and buprenorphine both increase sedation. Use Caution/Monitor.

            • chlordiazepoxide

              chlordiazepoxide and buprenorphine both increase sedation. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and buprenorphine both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              buprenorphine and chlorpromazine both increase sedation. Use Caution/Monitor.

            • chlorzoxazone

              chlorzoxazone and buprenorphine both increase sedation. Use Caution/Monitor.

            • cinnarizine

              cinnarizine and buprenorphine both increase sedation. Use Caution/Monitor.

            • clemastine

              clemastine and buprenorphine both increase sedation. Use Caution/Monitor.

            • clobazam

              buprenorphine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clomipramine

              buprenorphine and clomipramine both increase sedation. Use Caution/Monitor.

            • clonazepam

              clonazepam and buprenorphine both increase sedation. Use Caution/Monitor.

            • clorazepate

              clorazepate and buprenorphine both increase sedation. Use Caution/Monitor.

            • clozapine

              buprenorphine and clozapine both increase sedation. Use Caution/Monitor.

            • cobicistat

              cobicistat will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • codeine

              buprenorphine and codeine both increase sedation. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

            • crofelemer

              crofelemer increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclizine

              cyclizine and buprenorphine both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

              cyclobenzaprine and buprenorphine both increase sedation. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine and buprenorphine both increase sedation. Use Caution/Monitor.

            • dabrafenib

              dabrafenib will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dantrolene

              dantrolene and buprenorphine both increase sedation. Use Caution/Monitor.

            • darunavir

              darunavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Carefully titrate dose when initiating buprenorphine, buprenorphine/naloxone, or methadone with patients taking darunavir/cobicstat. When initiating cobicistat in patients taking buprenorphine, buprenorphine/naloxone, or methadone, adjust dose for buprenorphine, buprenorphine/naloxone, or methadone and monitor clinical signs and symptoms.

            • desflurane

              desflurane and buprenorphine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

            • desipramine

              buprenorphine and desipramine both increase sedation. Use Caution/Monitor.

            • deutetrabenazine

              buprenorphine and deutetrabenazine both increase sedation. Use Caution/Monitor.

            • dexamethasone

              dexamethasone will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dexchlorpheniramine

              dexchlorpheniramine and buprenorphine both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              buprenorphine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine and buprenorphine both increase sedation. Use Caution/Monitor.

            • dextromoramide

              buprenorphine and dextromoramide both increase sedation. Use Caution/Monitor.

            • diamorphine

              buprenorphine and diamorphine both increase sedation. Use Caution/Monitor.

            • diazepam

              diazepam and buprenorphine both increase sedation. Use Caution/Monitor.

            • difenoxin hcl

              buprenorphine and difenoxin hcl both increase sedation. Use Caution/Monitor.

            • dimenhydrinate

              dimenhydrinate and buprenorphine both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine and buprenorphine both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              buprenorphine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • dipipanone

              buprenorphine and dipipanone both increase sedation. Use Caution/Monitor.

            • dopexamine

              buprenorphine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dosulepin

              buprenorphine and dosulepin both increase sedation. Use Caution/Monitor.

            • doxepin

              buprenorphine and doxepin both increase sedation. Use Caution/Monitor.

            • doxylamine

              doxylamine and buprenorphine both increase sedation. Use Caution/Monitor.

            • droperidol

              buprenorphine and droperidol both increase sedation. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

              encorafenib, buprenorphine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enzalutamide

              enzalutamide will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • esketamine intranasal

              esketamine intranasal, buprenorphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estazolam

              estazolam and buprenorphine both increase sedation. Use Caution/Monitor.

            • ethanol

              buprenorphine and ethanol both increase sedation. Use Caution/Monitor.

            • etomidate

              etomidate and buprenorphine both increase sedation. Use Caution/Monitor.

            • etravirine

              etravirine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fedratinib

              fedratinib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenfluramine

              buprenorphine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • flibanserin

              buprenorphine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

            • fluphenazine

              buprenorphine and fluphenazine both increase sedation. Use Caution/Monitor.

            • flurazepam

              flurazepam and buprenorphine both increase sedation. Use Caution/Monitor.

            • fosamprenavir

              fosamprenavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. .

            • fosphenytoin

              fosphenytoin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • gabapentin

              gabapentin, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • gabapentin enacarbil

              gabapentin enacarbil, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • haloperidol

              buprenorphine and haloperidol both increase sedation. Use Caution/Monitor.

            • hydromorphone

              buprenorphine and hydromorphone both increase sedation. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and buprenorphine both increase sedation. Use Caution/Monitor.

            • iloperidone

              buprenorphine and iloperidone both increase sedation. Use Caution/Monitor.

              iloperidone increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imipramine

              buprenorphine and imipramine both increase sedation. Use Caution/Monitor.

            • indinavir

              indinavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. .

            • istradefylline

              istradefylline will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • ketamine

              ketamine and buprenorphine both increase sedation. Use Caution/Monitor.

            • ketotifen, ophthalmic

              buprenorphine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, buprenorphine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant, buprenorphine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • letermovir

              letermovir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • levorphanol

              buprenorphine and levorphanol both increase sedation. Use Caution/Monitor.

            • lofepramine

              buprenorphine and lofepramine both increase sedation. Use Caution/Monitor.

            • lofexidine

              buprenorphine and lofexidine both increase sedation. Use Caution/Monitor.

            • lopinavir

              lopinavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity.

            • loprazolam

              loprazolam and buprenorphine both increase sedation. Use Caution/Monitor.

            • lorazepam

              lorazepam and buprenorphine both increase sedation. Use Caution/Monitor.

            • lorlatinib

              lorlatinib will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lormetazepam

              lormetazepam and buprenorphine both increase sedation. Use Caution/Monitor.

            • loxapine

              buprenorphine and loxapine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              buprenorphine and loxapine inhaled both increase sedation. Use Caution/Monitor.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lurasidone

              lurasidone, buprenorphine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              buprenorphine and maprotiline both increase sedation. Use Caution/Monitor.

            • marijuana

              buprenorphine and marijuana both increase sedation. Use Caution/Monitor.

            • melatonin

              buprenorphine and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              buprenorphine and meperidine both increase sedation. Use Caution/Monitor.

            • meprobamate

              buprenorphine and meprobamate both increase sedation. Use Caution/Monitor.

            • metaxalone

              metaxalone and buprenorphine both increase sedation. Use Caution/Monitor.

            • methadone

              buprenorphine and methadone both increase sedation. Use Caution/Monitor.

            • methocarbamol

              methocarbamol and buprenorphine both increase sedation. Use Caution/Monitor.

            • methylenedioxymethamphetamine

              buprenorphine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • midazolam

              midazolam and buprenorphine both increase sedation. Use Caution/Monitor.

            • midazolam intranasal

              midazolam intranasal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • mirtazapine

              buprenorphine and mirtazapine both increase sedation. Use Caution/Monitor.

            • mitotane

              mitotane will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • morphine

              buprenorphine and morphine both increase sedation. Use Caution/Monitor.

            • motherwort

              buprenorphine and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              buprenorphine and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              buprenorphine and nabilone both increase sedation. Use Caution/Monitor.

            • nafcillin

              nafcillin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nalbuphine

              buprenorphine and nalbuphine both increase sedation. Use Caution/Monitor.

            • nelfinavir

              nelfinavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. .

            • nevirapine

              nevirapine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nortriptyline

              buprenorphine and nortriptyline both increase sedation. Use Caution/Monitor.

            • olanzapine

              buprenorphine and olanzapine both increase sedation. Use Caution/Monitor.

            • oliceridine

              oliceridine, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increases levels of buprenorphine and active metabolite norbuprenorphine; no dose adjustment of buprenorphine is required, but closely monitor for sedation and cognitive effects

            • opium tincture

              buprenorphine and opium tincture both increase sedation. Use Caution/Monitor.

            • orphenadrine

              orphenadrine and buprenorphine both increase sedation. Use Caution/Monitor.

            • osilodrostat

              osilodrostat and buprenorphine both increase QTc interval. Use Caution/Monitor.

            • oxazepam

              oxazepam and buprenorphine both increase sedation. Use Caution/Monitor.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • oxycodone

              buprenorphine and oxycodone both increase sedation. Use Caution/Monitor.

            • oxymorphone

              buprenorphine and oxymorphone both increase sedation. Use Caution/Monitor.

            • paliperidone

              buprenorphine and paliperidone both increase sedation. Use Caution/Monitor.

            • papaveretum

              buprenorphine and papaveretum both increase sedation. Use Caution/Monitor.

            • papaverine

              buprenorphine and papaverine both increase sedation. Use Caution/Monitor.

            • pegvisomant

              buprenorphine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

            • pentazocine

              buprenorphine and pentazocine both increase sedation. Use Caution/Monitor.

            • pentobarbital

              pentobarbital and buprenorphine both increase sedation. Use Caution/Monitor.

              pentobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • perampanel

              perampanel and buprenorphine both increase sedation. Use Caution/Monitor.

            • perphenazine

              buprenorphine and perphenazine both increase sedation. Use Caution/Monitor.

            • phenobarbital

              phenobarbital and buprenorphine both increase sedation. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • phenylephrine PO

              buprenorphine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • phenytoin

              phenytoin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pholcodine

              buprenorphine and pholcodine both increase sedation. Use Caution/Monitor.

            • pimozide

              buprenorphine and pimozide both increase sedation. Use Caution/Monitor.

            • pregabalin

              pregabalin, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone and buprenorphine both increase sedation. Use Caution/Monitor.

              primidone will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • prochlorperazine

              buprenorphine and prochlorperazine both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine and buprenorphine both increase sedation. Use Caution/Monitor.

            • propofol

              propofol and buprenorphine both increase sedation. Use Caution/Monitor.

            • propylhexedrine

              buprenorphine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              buprenorphine and protriptyline both increase sedation. Use Caution/Monitor.

            • quazepam

              quazepam and buprenorphine both increase sedation. Use Caution/Monitor.

            • quetiapine

              buprenorphine and quetiapine both increase sedation. Use Caution/Monitor.

            • ramelteon

              buprenorphine and ramelteon both increase sedation. Use Caution/Monitor.

            • remimazolam

              remimazolam, buprenorphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • ribociclib

              ribociclib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifabutin

              rifabutin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifampin

              rifampin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifapentine

              rifapentine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • risperidone

              buprenorphine and risperidone both increase sedation. Use Caution/Monitor.

            • ritonavir

              ritonavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity.

            • rolapitant

              rolapitant will increase the level or effect of buprenorphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

            • rucaparib

              rucaparib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • saquinavir

              saquinavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. .

            • scullcap

              buprenorphine and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital and buprenorphine both increase sedation. Use Caution/Monitor.

              secobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May also enhance CNS depressant effect of buprenorphine

            • sevoflurane

              sevoflurane and buprenorphine both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              buprenorphine and shepherd's purse both increase sedation. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of buprenorphine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of buprenorphine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.

            • St John's Wort

              St John's Wort will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • stiripentol

              stiripentol, buprenorphine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol, buprenorphine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • sufentanil

              buprenorphine and sufentanil both increase sedation. Use Caution/Monitor.

            • suvorexant

              suvorexant and buprenorphine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

            • tapentadol

              buprenorphine and tapentadol both increase sedation. Use Caution/Monitor.

            • tazemetostat

              tazemetostat will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • temazepam

              temazepam and buprenorphine both increase sedation. Use Caution/Monitor.

            • thioridazine

              buprenorphine and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              buprenorphine and thiothixene both increase sedation. Use Caution/Monitor.

            • tipranavir

              tipranavir will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • topiramate

              buprenorphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tramadol

              buprenorphine and tramadol both increase sedation. Use Caution/Monitor.

            • trazodone

              buprenorphine and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              triazolam and buprenorphine both increase sedation. Use Caution/Monitor.

            • triclofos

              triclofos and buprenorphine both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              buprenorphine and trifluoperazine both increase sedation. Use Caution/Monitor.

            • trimipramine

              buprenorphine and trimipramine both increase sedation. Use Caution/Monitor.

            • triprolidine

              triprolidine and buprenorphine both increase sedation. Use Caution/Monitor.

            • xylometazoline

              buprenorphine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziconotide

              buprenorphine and ziconotide both increase sedation. Use Caution/Monitor.

            • ziprasidone

              buprenorphine and ziprasidone both increase sedation. Use Caution/Monitor.

            • zotepine

              buprenorphine and zotepine both increase sedation. Use Caution/Monitor.

            Minor (7)

            • brimonidine

              brimonidine increases effects of buprenorphine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • dextroamphetamine

              dextroamphetamine increases effects of buprenorphine by unspecified interaction mechanism. Minor/Significance Unknown.

            • elvitegravir

              elvitegravir increases levels of buprenorphine by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects.

              elvitegravir decreases levels of naloxone by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects.

            • eucalyptus

              buprenorphine and eucalyptus both increase sedation. Minor/Significance Unknown.

            • lidocaine

              lidocaine increases toxicity of buprenorphine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

            • sage

              buprenorphine and sage both increase sedation. Minor/Significance Unknown.

            • ziconotide

              ziconotide, buprenorphine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

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            Adverse Effects

            >10%

            Headache (28-36.4%)

            Withdrawal syndrome (24-25.2%)

            Insomnia (14-23%)

            Pain (22.4%)

            Nausea (7-15%)

            Hyperhidrosis (14%)

            Asthenia (6.5-14%)

            Constipation (5-12.1%)

            Abdominal pain (11.2%)

            1-10%

            Diarrhea (10%)

            Vasodilation or peripheral edema (9.3%)

            Chills (6-7.5%)

            Vomiting (4-7.5%)

            Postmarketing Reports

            Adrenal insufficiency

            Anaphylaxis

            Serotonin syndrome

            Hepatotoxicity

            Glossodynia

            Glossitis

            Oral mucosal erythema

            Oral hypoesthesia Stomatitis

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            Warnings

            Contraindications

            Hypersensitivity

            Cautions

            Significant respiratory depression may occur with therapeutic doses

            Use with caution in hypothyroidism, preexisting respiratory compromise, obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve and kyphoscoliosis, myxedema, adrenocortical insufficiency, alcohol intoxication, alcohol withdrawal syndrome, coma, severe renal impairment, geriatric or debilitated patients, delirium tremens, toxic psychoses, kyphoscoliosis, prostatic hypertrophy, urethral stricture, comatose patients, central nervous system (CNS) depression, biliary tract dysfunction, severe hepatic impairment, head injury, intracranial lesions, and intracranial hypertension or conditions in which intracranial pressure (ICP) may be increased

            Use caution with concurrent use of other CNS depressants

            Respiratory sedation is dose-dependent; usual doses may depress respiration to same degree as 10 mg of parenteral morphine

            Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper

            Use caution in patients with history of ileus or bowel obstruction

            May cause orthostatic hypotension; use caution in patients with hypovolemia, cardiovascular disease, or drugs that may worsen hypertension

            Effects in CNS depression may impair ability to perform tasks that require mental alertness

            Life-threatening neonatal syndrome may occur in newborns following maternal exposure to opioids; treat according to protocols developed by neonatology experts; prescribers should discuss with patients importance and benefits of management of opioid addiction throughout pregnancy

            Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible

            Use caution when switching between formulations; certain sublingual film strengths may have greater bioavailability compared to the same strength of sublingual tablet; monitor for overdosing or underdosing when switching formulations

            Buprenorphine may precipitate acute narcotic withdrawal in opioid-dependent patients upon rapid discontinuation or rapid taper; taper dose gradually when discontinuing therapy

            Because it contains naloxone, drug is highly likely to produce marked and intense withdrawal signs and symptoms if misused parenterally by individual dependent on full opioid agonists such as heroin, morphine, or methadone

            May obscure diagnosis or clinical course of patients with acute abdominal conditions

            Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency

            Advise pregnant women receiving opioid addiction treatment with sublingual film of risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Due to risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose

            Drug can be abused in a manner similar to other opioids; consider this when prescribing or dispensing buprenorphine in situations when clinician is concerned about increased risk of misuse, abuse, or diversion

            Coadministration with benzodiazepines

            • Life-threating respiratory depression and death may occur; many, but not all, postmarketing reports regarding coma and death involved misuses by self-injection or were associated with concomitant use of benzodiazepines or other CNS depressants, including alcohol; warn patients of potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment
            • Concomitant use of buprenorphine and benzodiazepines or other CNS depressants increases 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
            • If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response; follow patients closely for signs and symptoms of respiratory depression and sedation
            • 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
            • Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient’s buprenorphine treatment and coordinate care to minimize the risks associated with concomitant use
            • If concomitant use with benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
            • Confirm patients are taking their medications as prescribed and are not diverting or supplementing with illicit drugs; toxicology screening should test for prescribed and illicit benzodiazepines

            Patient access to naloxone for emergency treatment of opioid overdose

            • Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
            • Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
            • Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
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            Pregnancy & Lactation

            Pregnancy

            Data on use of buprenorphine, one of the active ingredients are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure; there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations; the extremely limited data on sublingual naloxone exposure in pregnancy are not sufficient to evaluate a drug associated risk; dosage adjustments of buprenorphine may be required during pregnancy, even if patient was maintained on stable dose prior to pregnancy; withdrawal signs and symptoms should be monitored closely and dose adjusted as necessary

            Neonates whose mothers have been taking opioids long term may exhibit withdrawal signs, either at birth and/or in the nursery, because they have developed physical dependence; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts

            Lactation

            Caution should be exercised when therapy is administered to nursing women; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition; advise breastfeeding women taking buprenorphine products to monitor infant for increased drowsiness and breathing difficulties

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Buprenorphine: Semisynthetic narcotic mixed agonist-antagonist analgesic; exerts agonistic effects at mu and delta opioid receptors in CNS, as well as antagonistic effects at kappa opioid receptor

            Naloxone: Potent antagonist at mu opioid receptors and produces opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists when administered parenterally

            Absorption

            Suboxone

            • Peak plasma time: Buprenorphine, 1.53-1.72 hr; naloxone, 0.77-0.81 hr
            • Peak plasma concentration: Buprenorphine, 0.947-3.37 ng/mL; naloxone, 54.1-193 pg/mL

            Zubsolv

            • Bioavailability differs from that of Suboxone
            • Compared with Suboxone 8/2 mg, Zubsolv 5.7/1.4 mg provides equivalent buprenorphine exposure and 12% lower naloxone exposure

            Bunavail

            • Bioavailability differs from that of Suboxone
            • Compared with Suboxone 8/2 mg, Bunavail 4.2/0.7 mg provides equivalent buprenorphine exposure and 33% lower naloxone exposure
            • Coadministration of liquids reduced the systemic exposure up to 59% for buprenorphine and up to 76% for naloxone (depending on the pH of the liquid)

            Distribution

            Protein bound: Buprenorphine, 96% (primarily alpha and beta globulin); naloxone, 45% (primarily albumin)

            Metabolism

            Buprenorphine: Metabolized by N-dealkylation via CYP3A4 to norbuprenorphine (active metabolite) and by glucuronidation

            Naloxone: Metabolized by direct glucuronidation to naloxone-3-glucuronide, as well as by N-dealkylation and reduction of 6-oxo group

            Elimination

            Excretion: Buprenorphine, urine (30%) and feces (69%)

            Half-life

            • Suboxone, Zubsolv: 24-42 hr (buprenorphine); 2-12 hr (naloxone)
            • Cassipa: 35-37 hr (buprenorphine); 5.6-6.6 hr (naloxone)
            • Bunavail: 16.4-27.5 hr (buprenorphine); 1.9-2.4 hr (naloxone)
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            Administration

            Sublingual Administration

            Switching between SL tablet and SL film: Potential for greater bioavailability with SL film than with generic SL tablets (monitor for over- or underdosing)

            Instruct patient to rinse mouth with small volume of room-temperature water before placement of the SL film strip or tablet under their tongue

            High pH beverages should be avoided prior to dosing

            Place film/tablet under the tongue, close to the base on the left or right side; keep in place until completely dissolved

            Advise patients not to eat or drink anything until the film is completely dissolved

            Use entire tablet/film; do not chew, cut, or swallow SL or buccal preparations

            Bunavail Buccal Film Application

            Use the tongue to wet the inside of the cheek or rinse mouth with water to moisten the area immediately before placement

            Open package immediately prior to use

            Hold the buccal film with clean, dry fingers with the text (BN2, BN4, or BN6) facing up, THEN

            Place the side of the film with the text (BN2, BN4, or BN6) against the inside of the cheek

            Press and hold the film in place for 5 seconds

            Buccal film completely dissolves after applicationInstruct the patient to avoid manipulating the film(s) with the tongue or finger(s) and avoid drinking or eating food until the film(s) dissolve

            Multiple Bunavail films

            • If multiple films are needed, the patient should immediately apply the next film according to the steps above
            • When 2 films are required for one dose, the patient should place one film on the inside of one cheek and the other film on the inside of the other cheek
            • For doses requiring multiple films, no more than 2 films should be applied to the inside of one cheek at a time
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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.