buprenorphine buccal (Rx)

Brand and Other Names:Belbuca
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

buccal film: Schedule III

  • 75mcg
  • 150mcg
  • 300mcg
  • 450mcg
  • 600mcg
  • 750mcg
  • 900mcg

Chronic Severe Pain

Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Buccal film for oral buccal use only; apply to buccal mucosa q12hr

Initiate the dosing regimen for each patient individually, taking into account the patient’s severity of pain, response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse

Opioid-naïve

  • Initiate with 75 mcg film qDay or, if tolerated, q12hr for at least 4 days, then increase dose to 150 mcg q12hr
  • Individual titration to a dose that provides adequate analgesia and minimizes adverse reactions should proceed in increments of 150 mcg q12hr, no more frequently than every 4 days
  • Doses up to 450 mcg q12hr were studied in opioid-naïve patients in the clinical trials

Conversion from other opioids

  • There is a potential for buprenorphine to precipitate withdrawal in patients who are already on opioids
  • To reduce the risk of opioid withdrawal, taper patients ≤30 mg oral morphine sulfate equivalents (MSE) daily before beginning buprenorphine buccal
  • May supplement with prompt-acting opioid and nonopioid analgesic for break-through pain during taper
  • Following analgesic taper, base the starting dose on the patient’s daily opioid dose prior to taper, as described
    • Oral morphine equivalent <30 mg/day: Initiate with 75 mcg qDay or q12hr
    • Oral morphine equivalent 30-89 mg/day: Initiate with 150 mcg q12hr
    • Oral morphine equivalent 90-160 mg/day: Initiate with 300 mcg q12hr
    • Oral morphine equivalent >160 mg/day: Consider alternate analgesic
    • Buprenorphine buccal doses of 600 mcg, 750 mcg, and 900 mcg are only for use following titration from lower doses of buprenorphine buccal
    • Individual titration should proceed in increments of 150 mcg q12h, no more frequently than every 4 days

Conversion from methadone

  • Close monitoring is of particular importance when converting from methadone to other opioid agonists, including buprenorphine buccal
  • 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

Titration and maintenance dose

  • Individually titrate to a dose that provides adequate analgesia and minimizes adverse reactions
  • Continually reevaluate to assess the maintenance of pain control and the relative incidence of adverse reactions and monitor for the development of addiction, abuse, or misuse
  • Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration
  • During long-term therapy, periodically reassess the continued need for opioid analgesics
  • The minimum titration interval is 4 days, based on the pharmacokinetic profile and time to reach steady-state plasma levels
  • Individual titration should proceed in increments that do not exceed 150 mcg q12hr
  • Maximum dose: 900 mcg q12hr; do not exceed this dose because of potential for QTc interval prolongation
  • If pain is not adequately managed on buprenorphine buccal 900 mcg, consider an alternate analgesic
  • Patients who experience breakthrough pain may require dosage adjustment of buprenorphine or may need rescue medication with an appropriate dose of an immediate-release analgesic
  • If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the dose
  • If unacceptable opioid-related adverse reactions are observed, adjust the dose to obtain an appropriate balance between the management of pain and opioid-related adverse reactions

Dosage Modifications

Renal impairment: No dosage adjustment required for any level of renal impairment

Oral mucositis: In patients with known or suspected mucositis, reduce the starting dosage and titration incremental dosage by half compared with patients without mucositis

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment required
  • Moderate (Child-Pugh B): No dosage adjustment required; however, monitor these patients for signs and symptoms of toxicity or overdose
  • Severe (Child-Pugh C): Reduce the starting dose and reduce the titration dose by half that of patients with normal liver function, from 150 mcg to 75 mcg

Dosing Considerations

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 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)

Limitations of use

  • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients in whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
  • Not indicated as a PRN analgesic

Safety and efficacy not established

Although specific dose adjustments on the basis of advanced age are not required for pharmacokinetic reasons, use caution in the elderly population to ensure safe use

Clinical trials observed that some adverse effects (ie, respiratory depression, constipation, urinary retention) occur more frequently in elderly patients

See adult dosing

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Interactions

Interaction Checker

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            Contraindicated (1)

            • alvimopan

              alvimopan, buprenorphine buccal. receptor binding competition. Contraindicated. 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.

            Serious - Use Alternative (53)

            • alfentanil

              buprenorphine buccal, 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 buccal 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 buccal, 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

              buprenorphine buccal 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.

            • butorphanol

              buprenorphine buccal, 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 buccal, 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.

            • cimetidine

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

            • clonidine

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

            • codeine

              buprenorphine buccal, 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.

            • dextromoramide

              buprenorphine buccal, 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 buccal, 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 buccal. 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 buccal, 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 buccal, 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 buccal, 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 buccal, 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

              buprenorphine buccal 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, buprenorphine buccal. 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.

            • fentanyl intranasal

              buprenorphine buccal 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 intranasal, buprenorphine buccal. 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.

            • fentanyl transdermal

              buprenorphine buccal 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 transdermal, buprenorphine buccal. 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.

            • fentanyl transmucosal

              buprenorphine buccal 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.

              fentanyl transmucosal, buprenorphine buccal. 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.

            • hydrocodone

              buprenorphine buccal 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. .

            • hydromorphone

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

            • levorphanol

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

            • meperidine

              buprenorphine buccal, 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 buccal, 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.

            • metoclopramide intranasal

              buprenorphine buccal, 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.

            • morphine

              buprenorphine buccal, 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 buccal, 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.

            • oliceridine

              buprenorphine buccal, oliceridine. Other (see comment). Avoid or Use Alternate Drug. Comment: Concomitant use may reduce analgesic effect of oliceridine and/or precipitate withdrawal symptoms.

            • opium tincture

              buprenorphine buccal, opium tincture. 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.

            • oxycodone

              buprenorphine buccal, oxycodone. 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.

            • oxymorphone

              buprenorphine buccal, oxymorphone. 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.

            • ozanimod

              ozanimod and buprenorphine buccal both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • papaveretum

              buprenorphine buccal, papaveretum. 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.

            • pentazocine

              buprenorphine buccal, pentazocine. 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.

            • phenelzine

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

            • procarbazine

              procarbazine increases toxicity of buprenorphine buccal by unknown mechanism. Avoid or Use Alternate Drug. Do not use within 14 days of MAOI use. .

            • rasagiline

              rasagiline increases toxicity of buprenorphine buccal by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

            • selegiline

              selegiline increases toxicity of buprenorphine buccal by unknown mechanism. Avoid or Use Alternate Drug. Buprenorphine transdermal is not recommended for in patients who have received MAOI within 14 days, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

            • selegiline transdermal

              selegiline transdermal increases toxicity of buprenorphine buccal by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

            • selinexor

              selinexor, buprenorphine buccal. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

            • sodium oxybate

              buprenorphine buccal, sodium oxybate. 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.

            • sufentanil

              buprenorphine buccal, sufentanil. 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.

            • sufentanil SL

              buprenorphine buccal decreases effects of sufentanil SL by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of opioid mixed agonist/antagonist or partial agonist may reduce sufentail SL analgesic effect and/or precipitate withdrawal symptoms.

            • tapentadol

              buprenorphine buccal, tapentadol. 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.

            • tramadol

              buprenorphine buccal, tramadol. 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.

              tramadol, buprenorphine buccal. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

            • tranylcypromine

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

            • tucatinib

              tucatinib will increase the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • valerian

              valerian and buprenorphine buccal both increase sedation. Avoid or Use Alternate Drug.

            • voxelotor

              voxelotor will increase the level or effect of buprenorphine buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (217)

            • albuterol

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

            • alfentanil

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

            • alprazolam

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

            • amitriptyline

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

            • amobarbital

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

            • amoxapine

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

            • apalutamide

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

            • apomorphine

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

            • arformoterol

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

            • aripiprazole

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

            • armodafinil

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

            • atazanavir

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

            • azelastine

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

            • baclofen

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

            • belladonna and opium

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

            • benperidol

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

            • benzphetamine

              buprenorphine buccal 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 buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • brexanolone

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

            • brompheniramine

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

            • butabarbital

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

            • butalbital

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

            • butorphanol

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

            • caffeine

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

            • carbamazepine

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

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

            • carbinoxamine

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

            • carisoprodol

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

            • cenobamate

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

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chlorpheniramine

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

            • chlorpromazine

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

            • chlorzoxazone

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

            • cinnarizine

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

            • clemastine

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

            • clobazam

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

            • clonazepam

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

            • clorazepate

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

            • clozapine

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

            • codeine

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

            • crizotinib

              crizotinib increases levels of buprenorphine buccal 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 buccal 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 buccal both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

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

            • cyproheptadine

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

            • dabrafenib

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

            • dantrolene

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

            • darunavir

              darunavir increases levels of buprenorphine buccal 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 buccal both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

            • desipramine

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

            • dexamethasone

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

            • dexchlorpheniramine

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

            • dexfenfluramine

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

            • dexmedetomidine

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

            • dexmethylphenidate

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

            • dextroamphetamine

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

            • dextromoramide

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

            • diamorphine

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

            • diazepam

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

            • diethylpropion

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

            • difenoxin hcl

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

            • dimenhydrinate

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

            • diphenhydramine

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

            • diphenoxylate hcl

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

            • dipipanone

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

            • dobutamine

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

            • dopamine

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

            • dopexamine

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

            • dosulepin

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

            • doxepin

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

            • doxylamine

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

            • droperidol

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

            • efavirenz

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

            • elagolix

              elagolix will decrease the level or effect of buprenorphine buccal 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.

            • eltrombopag

              eltrombopag increases levels of buprenorphine buccal by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of buprenorphine buccal 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.

            • enzalutamide

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

            • ephedrine

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

            • epinephrine

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

            • epinephrine racemic

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

            • eslicarbazepine acetate

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

            • estazolam

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

            • ethanol

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

            • etomidate

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

            • etravirine

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

            • fenfluramine

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

            • flibanserin

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

            • fluphenazine

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

            • flurazepam

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

            • formoterol

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

            • fosamprenavir

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

            • gabapentin

              gabapentin, buprenorphine buccal. 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 buccal. 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 buccal and haloperidol both increase sedation. Use Caution/Monitor.

            • hydromorphone

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

            • hydroxyzine

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

            • iloperidone

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

              iloperidone increases levels of buprenorphine buccal 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 buccal and imipramine both increase sedation. Use Caution/Monitor.

            • indinavir

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

            • isoproterenol

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

            • istradefylline

              istradefylline will increase the level or effect of buprenorphine buccal 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 buccal both increase sedation. Use Caution/Monitor.

            • ketotifen, ophthalmic

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

            • lasmiditan

              lasmiditan, buprenorphine buccal. 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 buccal. 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.

            • levalbuterol

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

            • levorphanol

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

            • lisdexamfetamine

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

            • lofepramine

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

            • lofexidine

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

            • lopinavir

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

            • loprazolam

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

            • lorazepam

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

            • lormetazepam

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

            • loxapine

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

            • loxapine inhaled

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

            • lumacaftor/ivacaftor

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

            • lurasidone

              lurasidone, buprenorphine buccal. 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 buccal and maprotiline both increase sedation. Use Caution/Monitor.

            • marijuana

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

            • melatonin

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

            • meperidine

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

            • meprobamate

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

            • metaproterenol

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

            • metaxalone

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

            • methadone

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

            • methamphetamine

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

            • methocarbamol

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

            • methylenedioxymethamphetamine

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

            • midazolam

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

            • midazolam intranasal

              midazolam intranasal, buprenorphine buccal. 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.

            • midodrine

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

            • mirtazapine

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

            • mitotane

              buprenorphine buccal decreases levels of mitotane by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

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

            • modafinil

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

            • morphine

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

            • motherwort

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

            • moxonidine

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

            • nabilone

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

            • nafcillin

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

            • nalbuphine

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

            • nelfinavir

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

            • norepinephrine

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

            • nortriptyline

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

            • olanzapine

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

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir will increase the level or effect of buprenorphine buccal 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 buccal and opium tincture both increase sedation. Use Caution/Monitor.

            • orphenadrine

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

            • oxazepam

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

            • oxcarbazepine

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

            • oxycodone

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

            • oxymorphone

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

            • paliperidone

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

            • papaveretum

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

            • papaverine

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

            • pegvisomant

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

            • pentazocine

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

            • pentobarbital

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

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

            • perampanel

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

            • perphenazine

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

            • phendimetrazine

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

            • phenobarbital

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

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

            • phentermine

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

            • phenylephrine

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

            • phenylephrine PO

              buprenorphine buccal 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 buccal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pholcodine

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

            • pimozide

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

            • pirbuterol

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

            • pregabalin

              pregabalin, buprenorphine buccal. 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 buccal both increase sedation. Use Caution/Monitor.

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

            • prochlorperazine

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

            • promethazine

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

            • propofol

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

            • propylhexedrine

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

            • protriptyline

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

            • quazepam

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

            • quetiapine

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

            • ramelteon

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

            • rifabutin

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

            • rifampin

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

            • rifapentine

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

            • risperidone

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

            • ritonavir

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

            • rotigotine

              buprenorphine buccal and rotigotine both increase sedation. Use Caution/Monitor.

            • rucaparib

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

            • salmeterol

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

            • saquinavir

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

            • scullcap

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

            • secobarbital

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

            • sevoflurane

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

            • shepherd's purse

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

            • St John's Wort

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

            • sufentanil

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

            • suvorexant

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

            • tapentadol

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

            • tecovirimat

              tecovirimat will decrease the level or effect of buprenorphine buccal 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 buccal both increase sedation. Use Caution/Monitor.

            • terbutaline

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

            • thioridazine

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

            • thiothixene

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

            • topiramate

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

            • tramadol

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

            • trazodone

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

            • triazolam

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

            • triclofos

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

            • trifluoperazine

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

            • trimipramine

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

            • triprolidine

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

            • xylometazoline

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

            • yohimbine

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

            • ziconotide

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

            • ziprasidone

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

            • zotepine

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

            Minor (7)

            • brimonidine

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

            • dextroamphetamine

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

            • elvitegravir

              elvitegravir increases levels of buprenorphine buccal 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 buccal and eucalyptus both increase sedation. Minor/Significance Unknown.

            • lidocaine

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

            • sage

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

            • ziconotide

              ziconotide, buprenorphine buccal. 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%

            Open-label titration phase

            • Nausea, opioid-naive (50%)
            • Nausea, both opioid-naïve and opioid-tolerant (33%)
            • Nausea, opioid-tolerant (17%)
            • Constipation, opioid-naïve (13%)
            • Constipation, opioid-naïve and opioid-tolerant (11%)

            1-10%

            Open-label titration phase

            • Constipation, opioid-tolerant (8%)
            • Headache (8%)
            • Vomiting (7%)
            • Dizziness (6%)
            • Somnolence (6%)
            • Drug withdrawal syndrome: (1%)

            Postmarketing Reports

            Adrenal insufficiency

            Hepatotoxicity

            Serotonin syndrome

            Anaphylaxis

            Androgen deficiency

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            Warnings

            Black Box Warnings

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers
            • Healthcare providers are strongly encouraged to:
              • Complete a REMS-compliant education program
              • Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
              • Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
              • Consider other tools to improve patient, household, and community safety

            Addiction, abuse, and misuse

            • Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
            • Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation or following a dose increase

            Accidental exposure

            • Accidental exposure of even 1 dose, especially by children, can result in a fatal overdose

            Neonatal opioid withdrawal syndrome

            • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight
            • Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
            • If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Concomitant use with benzodiazepines or other CNS depressants

            • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death; reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to minimum required; and follow patients for signs and symptoms of respiratory depression and sedation

            Contraindications

            Significant respiratory depression

            Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment

            Known or suspected gastrointestinal obstruction, including paralytic ileus

            Hypersensitivity (eg, anaphylaxis) to buprenorphine

            Cautions

            Misuse, abuse, diversion: Partial agonist at the mu opioid receptor and a schedule III controlled opioid exposes users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids owing to the larger amount of active opioid present; screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of risk for overdose and death associated with use of additional CNS depressants including alcohol and illicit drugs (see Black Box Warnings)

            Life-threatening respiratory depression more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients (even to moderate therapeutic doses) (see Black Box Warnings); because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function

            Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black Box Warnings)

            Accidental exposure reported, including fatalities (see Black Box Warnings)

            Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension

            Risk of apnea in patients with chronic pulmonary disease; closely monitor these patients, when initiating and titrating therapy; alternatively, consider the use of alternative non-opioid analgesics in these patients (see Black Box Warnings and Contraindications)

            QTc prolongation observed in healthy individuals at 40 mcg/hr; avoid in patients with history of long QT syndrome or coadministration with class IA (eg, quinidine, procainamide, disopyramide) or class III (eg, sotalol, amiodarone, dofetilide) antiarrhythmics

            Head injury: Respiratory depressant effects of opioids may include carbon dioxide retention and lead to elevated CSF pressure

            Hypotensive effects: Can cause severe hypotension; caution with depleted blood volume or coadministration of drugs that that affect vasomotor tone (eg, phenothiazines), vasodilators, or antihypertensives

            Hepatoxicity: Cases of cytolytic hepatitis and hepatitis with jaundice observed in individuals receiving buprenorphine SL for opioid dependence treatment; increased risk for overdose with moderate or severe hepatic impairment (see Dosage Modifications)

            Anaphylactic reactions reported

            May cause sphincter of Oddi spasm and aggravate abdominal conditions, including ileus (see Contraindications)

            Similar to other opioids, may aggravate seizure disorders by lowering seizure threshold

            Patients with cancer who have oral mucositis may absorb buprenorphine more rapidly than intended and have higher plasma levels of buprenorphine (see Dosage Modifications)

            Special risk groups may experience increased adverse reactions; caution with alcoholism, delirium tremens, adrenocortical insufficiency, CNS depression, debilitation, kyphoscoliosis associated with respiratory compromise, myxedema or hypothyroidism, prostatic hypertrophy or urethral stricture, severe impairment of hepatic, pulmonary or renal function, and toxic psychosis

            Profound sedation, respiratory depression, coma, and death may result from concomitant use with other CNS depressants (see BBW); prescribe lowest effective dosages and minimum durations of concomitant use

            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; if concomitant use with benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose

            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

            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

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

            Opioid analgesic risk evaluation and mitigation strategy (REMS)

            • To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
            • Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
            • Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
            • Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
            • To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint

            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

            Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates; not recommended for use in women immediately prior to and during labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate

            Neonates whose mothers have been taking opioids long term may also 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

            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

            Elicits partial agonistic effects at the mu opioid receptor in the CNS, and antagonistic effects at the kappa opioid receptor

            Absorption

            Absolute bioavailability: 46-65%

            75-mcg single dose

            • Peak plasma concentration: 0.17 ng/mL
            • Peak plasma time: 3 hr
            • AUC (0-4 hr): 0.46 h·ng/mL
            • AUC (1 - ∞): 0.63 h·ng/mL

            300-mcg single dose

            • Peak plasma concentration: 0.47 ng/mL
            • Peak plasma time: 2.5 hr
            • AUC (0-4 hr): 2 h·ng/mL
            • AUC (1 - ∞): 2.3 h·ng/mL

            1200-mcg single dose

            • Peak plasma concentration: 1.43 ng/mL
            • Peak plasma time: 3 hr
            • AUC (0-4 hr): 9.6 h·ng/mL
            • AUC (1 - ∞): 10.5 h·ng/mL

            Food and beverage decrease systemic exposure

            • Systemic exposure to buprenorphine was reduced by 23-27% by the ingestion of liquids (cold, hot, and room temperature water) during film administration
            • Systemic exposure also reduced if coadministration with low pH liquid (eg, decaffeinated cola) by ~37%
            • The consumption of food and liquids should be avoided until the buccal film has completely dissolved

            Distribution

            Protein bound 96%; primarily to alpha and beta globulin

            Metabolism

            Undergoes both N-dealkylation to norbuprenorphine and glucuronidation

            The N-dealkylation pathway is mediated primarily by CYP3A4

            Norbuprenorphine, the major metabolite, can further undergo glucuronidation

            Elimination

            Half-life: 27.6 hr

            Excretion: 30% urine; 69% feces

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            Administration

            Instructions

            Instruct patients not to use if the pouch seal is broken or the buccal film is cut, damaged, or changed in any way

            Buccal film for oral buccal use only; apply to buccal mucosa q12hr

            Do not apply to areas of the mouth with any open sores or lesions

            Monitor patients closely for respiratory depression, especially within the first 24-72 hr after initiating therapy and following dosage increases; adjust the dosage accordingly

            Also see Adult Dosing for titration and maintenance dosing

            Buccal Application

            First, the patient must use the tongue to wet the inside of the cheek or rinse the mouth with water to wet the area for placement of buprenorphine buccal

            Buprenorphine is then applied immediately after removal from the individually sealed package

            The yellow side of the Belbuca film is placed against the inside of the cheek; the entire film is held in place with clean, dry fingers for 5 seconds and then left in place on the inside of the cheek until fully dissolved

            The buccal film adheres to the moist buccal mucosa and will completely dissolve after application, usually within 30 minutes

            The film should not be manipulated with the tongue or finger(s)

            Avoid eating food and drinking liquids until the film has dissolved

            A buprenorphine buccal film that is chewed or swallowed may result in lower peak concentrations and lower bioavailability than when used as directed

            Discontinuation

            When a patient no longer requires therapy with buprenorphine buccal, use a gradual downward titration of the dose to prevent signs and symptoms of withdrawal in the physically dependent patient

            Do not abruptly discontinue

            Storage

            Store at controlled room temperature (25°C [77°F]); excursions permitted to 15-30°C (59-86ºF)

            Advise patients to store buprenorphine-containing medications safely and out of sight and reach of children

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            Images

            No images available for this drug.
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            Patient Handout

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

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            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.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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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.