buprenorphine, long-acting injection (Rx)

Brand and Other Names:Sublocade, Brixadi

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injection, long-acting subcutaneous (monthly dosing): Schedule III

  • 64mg/0.18mL (Brixadi)
  • 96mg/0.27mL (Brixadi)
  • 100mg/0.5mL (Sublocade)
  • 128mg/0.36mL (Brixadi)
  • 300mg/1.5mL (Sublocade)
  • Available as prefilled single-dose syringe with 19-gauge 5/8-inch needle (Sublocade) or 23-gauge 1/2-inch needle (Brixadi)

injection, long-acting subcutaneous (weekly dosing): Schedule III

  • 8mg/0.16mL (Brixadi)
  • 16mg/0.32mL (Brixadi)
  • 24mg/0.48mL (Brixadi)
  • 32mg/0.64mL (Brixadi)
  • Available as prefilled single-dose syringe with 23-gauge 1/2-inch needle (Brixadi)

Opioid Use Disorder

Sublocade

  • Indicated for moderate-to-severe opioid use disorder (OUD) in adults who have initiated treatment with a transmucosal buprenorphine-containing product and have been on a stable dose of transmucosal buprenorphine treatment for ≥7 days
  • Prescribe as part of a complete treatment plan that includes counseling and psychosocial support
  • 300 mg SC once monthly for the first 2 months, followed by a maintenance dose of 100 mg/month
  • May increase maintenance dose to 300 mg monthly if 100-mg dose tolerated, but do not demonstrate a satisfactory clinical response, as evidenced by self-reported illicit opioid use or urine drug screens positive for illicit opioid use

Brixadi

  • Indicated for moderate-to-severe OUD in adults who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine
  • Not currently receiving buprenorphine treatment (once weekly dosing)
    • Recommended weekly target dose: 24 mg SC q7days
    • Titrate up over first week as follows
    • To avoid precipitating an opioid withdrawal syndrome, administer a test dose of transmucosal buprenorphine 4 mg when objective signs of mild to moderate withdrawal appear
    • If dose of transmucosal buprenorphine is tolerated without precipitated withdrawal, administer first dose of Brixadi (weekly) 16 mg SC
    • Administer an additional dose of 8 mg Brixadi (weekly) within 3 days of the first dose to achieve the recommended 24-mg (weekly) dose
    • If needed, during this first week of treatment, administer an additional 8 mg dose, waiting at least 24 hr after previous injection, for a total weekly dose of 32 mg
    • Administer subsequent weekly injections based on the total weekly dose that was established during Week 1
    • Dosage adjustments can be made at weekly appointments
    • Maximum weekly dose is 32 mg
  • Switching from transmucosal buprenorphine to Brixadi weekly
    • Administer q7days; to avoid missed doses, may administer weekly dose up to 2 days before or after weekly time point
    • ≤6 mg SL: 8 mg SC
    • 8-10 mg SL: 16 mg SC
    • 12-16 mg SL: 24 mg SC
    • 18-24 mg SL: 32 mg SC
  • Switching from transmucosal buprenorphine to Brixadi monthly
    • Administer q28days; to avoid missed doses, may administer monthly dose up to 1 week before or after monthly time point
    • ≤6 mg SL: N/A
    • 8-10 mg SL: 64 mg SC
    • 12-16 mg SL: 96 mg SC
    • 18-24 mg SL: 128 mg SC
  • Transitioning between Brixadi weekly and monthly
    • 16 mg/week SC: Give 64 mg SC monthly
    • 24 mg/week SC: Give 96 mg SC monthly
    • 32 mg/week SC: Give 128 mg SC monthly
  • Brixadi dose adjustments
    • An additional 8 mg (weekly) injection may be administered, based on clinical judgment during a dosing interval up to maximum of 32 mg/week (Brixadi weekly) or 128 mg/month (Brixadi monthly)

Dosage Modifications

Renal impairment

  • Studies did not include patients with renal impairment

Hepatic impairment

  • Preexisting moderate or severe
    • Because of the long‐acting nature of these products, dosage adjustments are not rapidly reflected in plasma buprenorphine levels
    • Because buprenorphine levels cannot be rapidly adjusted, patients with pre‐existing moderate-to-severe hepatic impairment are not candidates for treatment

Dosing Considerations

Patient selection

  • For use as part of a complete treatment plan that includes counseling and psychosocial support
  • Sublocade
    • Appropriate patients for buprenorphine long-acting SC are adults who have initiated treatment on a transmucosal buprenorphine-containing product delivering the equivalent of 8-24 mg/day for at least 7 days
  • Brixadi
    • Brixadi weekly: Adults who have tolerated a single 4-mg transmucosal dose of buprenorphine
    • Brixadi (weekly or monthly): Adults who are currently being treated with transmucosal buprenorphine

Clinical supervision

  • Periodic assessment is necessary to determine effectiveness of the treatment plan and overall patient progress
  • When evaluating, examine the injection site for signs of infection or evidence of tampering or attempts to remove the depot
  • Owing to the chronic nature of opioid use disorder, the need for continuing medication-assisted treatment should be reevaluated periodically
  • There is no maximum recommended duration of maintenance treatment
  • For some patients, treatment may continue indefinitely
  • If considering stopping treatment, the clinical status of the patient should be considered

Removal of the depot

  • Sublocade
    • Forms a solid mass (depot) upon contact with body fluids
    • If depot must be removed, it can be surgically excised under local anesthesia within 14 days of injection; only the most recently injected depot can be removed
    • Handled disposalwith adequate security, accountability, and proper disposal, per facility procedure for a Schedule III drug product and pharmaceutical biohazardous waste, and per applicable federal, state, and local regulations
    • Residual plasma concentrations from previous injections decreases gradually over subsequent months
    • Following removal, monitor for signs and symptoms of withdrawal
  • Brixadi
    • Removal is not recommended
    • Forms a biodegradable liquid crystalline gel upon injection that is not always palpable and may not be conducive to surgical removal

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)

<17 years: Safety and efficacy not established

Clinical trials did not include sufficient numbers of individuals aged ≥65 y to determine whether they responded differently than younger individuals

Owing to possible decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in geriatric patients, the decision to prescribe buprenorphine long-acting SC injection should be made cautiously in individuals aged ≥65 y

If prescribed in geriatric patients, monitor for signs and symptoms of toxicity or overdose

Next:

Interactions

Interaction Checker

and buprenorphine, long-acting injection

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            Contraindicated (7)

            • dronedarone

              buprenorphine, long-acting injection and dronedarone both increase QTc interval. Contraindicated.

            • fezolinetant

              buprenorphine, long-acting injection will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • fluconazole

              buprenorphine, long-acting injection and fluconazole both increase QTc interval. Contraindicated.

            • lefamulin

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

            • posaconazole

              buprenorphine, long-acting injection and posaconazole both increase QTc interval. Contraindicated.

            • thalidomide

              buprenorphine, long-acting injection and thalidomide both increase sedation. Contraindicated.

            • thioridazine

              buprenorphine, long-acting injection and thioridazine both increase QTc interval. Contraindicated.

            Serious - Use Alternative (218)

            • abametapir

              abametapir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • acrivastine

              acrivastine and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • alfentanil

              buprenorphine, long-acting injection and alfentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • alprazolam

              buprenorphine, long-acting injection and alprazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • amiodarone

              buprenorphine, long-acting injection and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

            • amisulpride

              buprenorphine, long-acting injection and amisulpride both increase QTc interval. Avoid or Use Alternate Drug.

              amisulpride and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • amitriptyline

              buprenorphine, long-acting injection and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • amobarbital

              buprenorphine, long-acting injection and amobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • amoxapine

              buprenorphine, long-acting injection and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.

            • anagrelide

              buprenorphine, long-acting injection and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of buprenorphine, long-acting injection 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.

            • apomorphine

              buprenorphine, long-acting injection and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • aripiprazole

              buprenorphine, long-acting injection and aripiprazole both increase QTc interval. Avoid or Use Alternate Drug.

            • arsenic trioxide

              buprenorphine, long-acting injection and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

              buprenorphine, long-acting injection and artemether both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              buprenorphine, long-acting injection and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine

              buprenorphine, long-acting injection and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

              asenapine and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • asenapine transdermal

              asenapine transdermal and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • atomoxetine

              buprenorphine, long-acting injection and atomoxetine both increase QTc interval. Avoid or Use Alternate Drug.

            • avapritinib

              avapritinib and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • azithromycin

              buprenorphine, long-acting injection and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.

            • baclofen

              buprenorphine, long-acting injection and baclofen both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • bedaquiline

              buprenorphine, long-acting injection and bedaquiline both increase QTc interval. Avoid or Use Alternate Drug.

            • benzhydrocodone/acetaminophen

              buprenorphine, long-acting injection 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.

              benzhydrocodone/acetaminophen and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • brexpiprazole

              brexpiprazole and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • brimonidine

              brimonidine and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • brivaracetam

              brivaracetam and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • buprenorphine subdermal implant

              buprenorphine subdermal implant and buprenorphine, long-acting injection both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • butabarbital

              buprenorphine, long-acting injection and butabarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • butalbital

              buprenorphine, long-acting injection and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • butorphanol

              buprenorphine, long-acting injection and butorphanol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • carisoprodol

              buprenorphine, long-acting injection and carisoprodol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • ceritinib

              buprenorphine, long-acting injection and ceritinib both increase QTc interval. Avoid or Use Alternate Drug.

            • chlordiazepoxide

              buprenorphine, long-acting injection and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • chloroquine

              buprenorphine, long-acting injection and chloroquine both increase QTc interval. Avoid or Use Alternate Drug.

            • chlorpheniramine

              buprenorphine, long-acting injection and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • chlorpromazine

              buprenorphine, long-acting injection and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and chlorpromazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • chlorzoxazone

              buprenorphine, long-acting injection and chlorzoxazone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • ciprofloxacin

              buprenorphine, long-acting injection and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • citalopram

              buprenorphine, long-acting injection and citalopram both increase QTc interval. Avoid or Use Alternate Drug.

            • clarithromycin

              buprenorphine, long-acting injection and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

            • clobazam

              buprenorphine, long-acting injection and clobazam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • clomipramine

              buprenorphine, long-acting injection and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and clomipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • clonazepam

              buprenorphine, long-acting injection and clonazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • clonidine

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

            • clorazepate

              buprenorphine, long-acting injection and clorazepate both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • clozapine

              buprenorphine, long-acting injection and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

            • codeine

              buprenorphine, long-acting injection and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • crizotinib

              buprenorphine, long-acting injection and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • cyclobenzaprine

              buprenorphine, long-acting injection and cyclobenzaprine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • dantrolene

              buprenorphine, long-acting injection and dantrolene both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • dasatinib

              buprenorphine, long-acting injection and dasatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • degarelix

              buprenorphine, long-acting injection and degarelix both increase QTc interval. Avoid or Use Alternate Drug.

            • desflurane

              buprenorphine, long-acting injection and desflurane both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and desflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • desipramine

              buprenorphine, long-acting injection and desipramine both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and desipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • deutetrabenazine

              buprenorphine, long-acting injection and deutetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and deutetrabenazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • diazepam

              buprenorphine, long-acting injection and diazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • diazepam intranasal

              diazepam intranasal, buprenorphine, long-acting injection. 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.

            • disopyramide

              buprenorphine, long-acting injection and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

            • dofetilide

              buprenorphine, long-acting injection and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

            • dolasetron

              buprenorphine, long-acting injection and dolasetron both increase QTc interval. Avoid or Use Alternate Drug.

            • donepezil

              buprenorphine, long-acting injection and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

            • doxepin

              buprenorphine, long-acting injection and doxepin both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • droperidol

              buprenorphine, long-acting injection and droperidol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • efavirenz

              buprenorphine, long-acting injection and efavirenz both increase QTc interval. Avoid or Use Alternate Drug.

            • eliglustat

              buprenorphine, long-acting injection and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.

            • encorafenib

              buprenorphine, long-acting injection and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • entrectinib

              buprenorphine, long-acting injection and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • eribulin

              buprenorphine, long-acting injection and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin base

              buprenorphine, long-acting injection and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              buprenorphine, long-acting injection and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              buprenorphine, long-acting injection and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin stearate

              buprenorphine, long-acting injection and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

            • escitalopram

              buprenorphine, long-acting injection and escitalopram both increase QTc interval. Avoid or Use Alternate Drug.

            • esketamine intranasal

              buprenorphine, long-acting injection and esketamine intranasal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • estazolam

              buprenorphine, long-acting injection and estazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl

              buprenorphine, long-acting injection and fentanyl both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl intranasal

              buprenorphine, long-acting injection and fentanyl intranasal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl iontophoretic transdermal system

              buprenorphine, long-acting injection and fentanyl iontophoretic transdermal system both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl transdermal

              buprenorphine, long-acting injection and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fentanyl transmucosal

              buprenorphine, long-acting injection and fentanyl transmucosal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fexinidazole

              fexinidazole will increase the level or effect of buprenorphine, long-acting injection 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.

              buprenorphine, long-acting injection and fexinidazole both increase QTc interval. Avoid or Use Alternate Drug.

            • fingolimod

              buprenorphine, long-acting injection and fingolimod both increase QTc interval. Avoid or Use Alternate Drug.

            • flecainide

              buprenorphine, long-acting injection and flecainide both increase QTc interval. Avoid or Use Alternate Drug.

            • fluoxetine

              buprenorphine, long-acting injection and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug.

            • flurazepam

              buprenorphine, long-acting injection and flurazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • fluvoxamine

              buprenorphine, long-acting injection and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug.

            • foscarnet

              buprenorphine, long-acting injection and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

            • fostemsavir

              buprenorphine, long-acting injection and fostemsavir both increase QTc interval. Avoid or Use Alternate Drug.

            • gabapentin

              buprenorphine, long-acting injection and gabapentin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • gemifloxacin

              buprenorphine, long-acting injection and gemifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • gemtuzumab

              buprenorphine, long-acting injection and gemtuzumab both increase QTc interval. Avoid or Use Alternate Drug.

            • gilteritinib

              buprenorphine, long-acting injection and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.

            • glasdegib

              buprenorphine, long-acting injection and glasdegib both increase QTc interval. Avoid or Use Alternate Drug.

            • goserelin

              buprenorphine, long-acting injection and goserelin both increase QTc interval. Avoid or Use Alternate Drug.

            • granisetron

              buprenorphine, long-acting injection and granisetron both increase QTc interval. Avoid or Use Alternate Drug.

            • haloperidol

              buprenorphine, long-acting injection and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • histrelin

              buprenorphine, long-acting injection and histrelin both increase QTc interval. Avoid or Use Alternate Drug.

            • hydrocodone

              buprenorphine, long-acting injection 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. .

              buprenorphine, long-acting injection and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • hydromorphone

              buprenorphine, long-acting injection and hydromorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • hydroxychloroquine sulfate

              buprenorphine, long-acting injection and hydroxychloroquine sulfate both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxyzine

              buprenorphine, long-acting injection and hydroxyzine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • ibutilide

              buprenorphine, long-acting injection and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

            • iloperidone

              buprenorphine, long-acting injection and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • imipramine

              buprenorphine, long-acting injection and imipramine both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and imipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • inotuzumab

              buprenorphine, long-acting injection and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.

            • isoflurane

              buprenorphine, long-acting injection and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and isoflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • itraconazole

              buprenorphine, long-acting injection and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib will decrease the level or effect of buprenorphine, long-acting injection 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.

              buprenorphine, long-acting injection and ivosidenib both decrease QTc interval. Avoid or Use Alternate Drug.

            • lapatinib

              buprenorphine, long-acting injection and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • lefamulin

              buprenorphine, long-acting injection and lefamulin both increase QTc interval. Avoid or Use Alternate Drug.

            • lenvatinib

              buprenorphine, long-acting injection and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • leuprolide

              buprenorphine, long-acting injection and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.

            • levofloxacin

              buprenorphine, long-acting injection and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • lithium

              buprenorphine, long-acting injection and lithium both increase QTc interval. Avoid or Use Alternate Drug.

            • lofexidine

              buprenorphine, long-acting injection and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

            • lonafarnib

              lonafarnib will increase the level or effect of buprenorphine, long-acting injection 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.

            • loperamide

              buprenorphine, long-acting injection and loperamide both increase QTc interval. Avoid or Use Alternate Drug.

            • lopinavir

              buprenorphine, long-acting injection and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • lorazepam

              buprenorphine, long-acting injection and lorazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • macimorelin

              buprenorphine, long-acting injection and macimorelin both increase QTc interval. Avoid or Use Alternate Drug.

            • maprotiline

              buprenorphine, long-acting injection and maprotiline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • mefloquine

              buprenorphine, long-acting injection and mefloquine both increase QTc interval. Avoid or Use Alternate Drug.

            • metaxalone

              buprenorphine, long-acting injection and metaxalone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • methadone

              buprenorphine, long-acting injection and methadone both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and methadone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • methocarbamol

              buprenorphine, long-acting injection and methocarbamol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • methohexital

              buprenorphine, long-acting injection and methohexital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • metoclopramide intranasal

              buprenorphine, long-acting injection, 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.

            • midazolam

              buprenorphine, long-acting injection and midazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • midostaurin

              buprenorphine, long-acting injection and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

            • mifepristone

              buprenorphine, long-acting injection and mifepristone both increase QTc interval. Avoid or Use Alternate Drug.

            • mirtazapine

              buprenorphine, long-acting injection and mirtazapine both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and mirtazapine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • mobocertinib

              buprenorphine, long-acting injection and mobocertinib both increase QTc interval. Avoid or Use Alternate Drug.

            • morphine

              buprenorphine, long-acting injection and morphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • moxifloxacin

              buprenorphine, long-acting injection and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • nalbuphine

              buprenorphine, long-acting injection and nalbuphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • nilotinib

              buprenorphine, long-acting injection and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • nortriptyline

              buprenorphine, long-acting injection and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and nortriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • octreotide

              buprenorphine, long-acting injection and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

            • ofloxacin

              buprenorphine, long-acting injection and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • olanzapine

              buprenorphine, long-acting injection and olanzapine both increase QTc interval. Avoid or Use Alternate Drug. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • oliceridine

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

              buprenorphine, long-acting injection and oliceridine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • olopatadine intranasal

              buprenorphine, long-acting injection and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • ondansetron

              buprenorphine, long-acting injection and ondansetron both increase QTc interval. Avoid or Use Alternate Drug.

            • orphenadrine

              buprenorphine, long-acting injection and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • osilodrostat

              buprenorphine, long-acting injection and osilodrostat both increase QTc interval. Avoid or Use Alternate Drug. Dose dependent QT prolongation - avoid drugs known to prolong the QT interval

            • osimertinib

              buprenorphine, long-acting injection and osimertinib both increase QTc interval. Avoid or Use Alternate Drug.

            • oxaliplatin

              buprenorphine, long-acting injection and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

            • oxazepam

              buprenorphine, long-acting injection and oxazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • oxycodone

              buprenorphine, long-acting injection and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • oxymorphone

              buprenorphine, long-acting injection and oxymorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • ozanimod

              ozanimod and buprenorphine, long-acting injection 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.

              buprenorphine, long-acting injection and ozanimod both increase QTc interval. Avoid or Use Alternate Drug.

            • paliperidone

              buprenorphine, long-acting injection and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • panobinostat

              buprenorphine, long-acting injection and panobinostat both increase QTc interval. Avoid or Use Alternate Drug.

            • pasireotide

              buprenorphine, long-acting injection and pasireotide both increase QTc interval. Avoid or Use Alternate Drug.

            • pazopanib

              buprenorphine, long-acting injection and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

            • pentamidine

              buprenorphine, long-acting injection and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

            • pentazocine

              buprenorphine, long-acting injection and pentazocine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • pentobarbital

              buprenorphine, long-acting injection and pentobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • pheniramine

              buprenorphine, long-acting injection and pheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • phenobarbital

              buprenorphine, long-acting injection and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • pimavanserin

              buprenorphine, long-acting injection and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

            • pimozide

              buprenorphine, long-acting injection and pimozide both increase QTc interval. Contraindicated.

            • pitolisant

              buprenorphine, long-acting injection and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

            • ponesimod

              buprenorphine, long-acting injection and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

            • pregabalin

              buprenorphine, long-acting injection and pregabalin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • primaquine

              buprenorphine, long-acting injection and primaquine both increase QTc interval. Avoid or Use Alternate Drug.

            • procainamide

              buprenorphine, long-acting injection and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

            • prochlorperazine

              buprenorphine, long-acting injection and prochlorperazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • promethazine

              buprenorphine, long-acting injection and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • propafenone

              buprenorphine, long-acting injection and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

            • propofol

              buprenorphine, long-acting injection and propofol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • protriptyline

              buprenorphine, long-acting injection and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and protriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • quazepam

              buprenorphine, long-acting injection and quazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • quetiapine

              buprenorphine, long-acting injection and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and quetiapine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • quinidine

              buprenorphine, long-acting injection and quinidine both increase QTc interval. Avoid or Use Alternate Drug.

            • quinine

              buprenorphine, long-acting injection and quinine both increase QTc interval. Avoid or Use Alternate Drug.

            • remimazolam

              buprenorphine, long-acting injection and remimazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • ribociclib

              buprenorphine, long-acting injection and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • rilpivirine

              buprenorphine, long-acting injection and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

            • risperidone

              buprenorphine, long-acting injection and risperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • romidepsin

              buprenorphine, long-acting injection and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

            • saquinavir

              buprenorphine, long-acting injection and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • scopolamine

              buprenorphine, long-acting injection and scopolamine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • selinexor

              selinexor, buprenorphine, long-acting injection. 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.

            • selpercatinib

              buprenorphine, long-acting injection and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • sertraline

              buprenorphine, long-acting injection and sertraline both increase QTc interval. Avoid or Use Alternate Drug.

            • sevoflurane

              buprenorphine, long-acting injection and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and sevoflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • siponimod

              buprenorphine, long-acting injection and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

            • solifenacin

              buprenorphine, long-acting injection and solifenacin both increase QTc interval. Avoid or Use Alternate Drug.

            • sorafenib

              buprenorphine, long-acting injection and sorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • sotalol

              buprenorphine, long-acting injection and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

            • sufentanil SL

              buprenorphine, long-acting injection 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.

            • sunitinib

              buprenorphine, long-acting injection and sunitinib both increase QTc interval. Avoid or Use Alternate Drug.

            • tacrolimus

              buprenorphine, long-acting injection and tacrolimus both increase QTc interval. Avoid or Use Alternate Drug.

            • tapentadol

              buprenorphine, long-acting injection and tapentadol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • telavancin

              buprenorphine, long-acting injection and telavancin both increase QTc interval. Avoid or Use Alternate Drug.

            • temazepam

              buprenorphine, long-acting injection and temazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • tetrabenazine

              buprenorphine, long-acting injection and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

              buprenorphine, long-acting injection and tetrabenazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • thioridazine

              buprenorphine, long-acting injection and thioridazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • tizanidine

              buprenorphine, long-acting injection and tizanidine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • toremifene

              buprenorphine, long-acting injection and toremifene both increase QTc interval. Avoid or Use Alternate Drug.

            • tramadol

              buprenorphine, long-acting injection and tramadol both increase sedation. Avoid or Use Alternate Drug.

            • trazodone

              buprenorphine, long-acting injection and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

            • triazolam

              buprenorphine, long-acting injection and triazolam both increase sedation. Avoid or Use Alternate Drug.

            • triclabendazole

              buprenorphine, long-acting injection and triclabendazole both increase QTc interval. Avoid or Use Alternate Drug.

            • trimipramine

              buprenorphine, long-acting injection and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.

            • triptorelin

              buprenorphine, long-acting injection and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.

            • tucatinib

              tucatinib will increase the level or effect of buprenorphine, long-acting injection 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.

            • vandetanib

              buprenorphine, long-acting injection and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.

            • vardenafil

              buprenorphine, long-acting injection and vardenafil both increase QTc interval. Avoid or Use Alternate Drug.

            • vemurafenib

              buprenorphine, long-acting injection and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • venlafaxine

              buprenorphine, long-acting injection and venlafaxine both decrease QTc interval. Avoid or Use Alternate Drug.

            • voclosporin

              buprenorphine, long-acting injection and voclosporin both increase QTc interval. Avoid or Use Alternate Drug.

            • voriconazole

              buprenorphine, long-acting injection and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • vorinostat

              buprenorphine, long-acting injection and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.

            • voxelotor

              voxelotor will increase the level or effect of buprenorphine, long-acting injection 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.

            • ziprasidone

              buprenorphine, long-acting injection and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

            Monitor Closely (300)

            • acetaminophen/phenyltoloxamine

              buprenorphine, long-acting injection and acetaminophen/phenyltoloxamine both increase sedation. Use Caution/Monitor.

            • albuterol

              buprenorphine, long-acting injection and albuterol both increase QTc interval. Use Caution/Monitor.

            • alfentanil

              alfentanil 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.

            • alfuzosin

              buprenorphine, long-acting injection and alfuzosin both increase QTc interval. Use Caution/Monitor.

            • alprazolam

              alprazolam 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.

            • amiloride

              buprenorphine, long-acting injection decreases effects of amiloride by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • amiodarone

              amiodarone will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • amitriptyline

              amitriptyline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • amobarbital

              amobarbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              amobarbital 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.

            • amoxapine

              amoxapine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

              buprenorphine, long-acting injection and amoxapine both increase sedation. Use Caution/Monitor.

            • amphetamine

              amphetamine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • amphetamine polistirex

              amphetamine polistirex, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • apalutamide

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

            • aprepitant

              aprepitant will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • arbaclofen

              buprenorphine, long-acting injection increases effects of arbaclofen by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • arformoterol

              buprenorphine, long-acting injection and arformoterol both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

              aripiprazole 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.

              buprenorphine, long-acting injection and aripiprazole both increase sedation. Use Caution/Monitor.

            • armodafinil

              armodafinil will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • asenapine

              asenapine 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.

            • atazanavir

              atazanavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • atracurium

              atracurium 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.

            • atropine

              buprenorphine, long-acting injection increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • baclofen

              buprenorphine, long-acting injection increases effects of baclofen by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • belzutifan

              belzutifan will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • bendroflumethiazide

              buprenorphine, long-acting injection decreases effects of bendroflumethiazide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • bicalutamide

              bicalutamide will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • bosentan

              bosentan will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • brexanolone

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

            • bumetanide

              buprenorphine, long-acting injection decreases effects of bumetanide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • buprenorphine

              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.

            • buprenorphine transdermal

              buprenorphine transdermal 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.

            • buspirone

              buspirone 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 will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              butabarbital 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.

            • butalbital

              butalbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              butalbital 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.

            • butorphanol

              butorphanol 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.

            • carbamazepine

              carbamazepine will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • carbinoxamine

              buprenorphine, long-acting injection and carbinoxamine both increase sedation. Use Caution/Monitor.

            • cariprazine

              cariprazine 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.

              buprenorphine, long-acting injection and cariprazine both increase sedation. Use Caution/Monitor.

            • carisoprodol

              buprenorphine, long-acting injection increases effects of carisoprodol by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • cenobamate

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

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

            • ceritinib

              ceritinib will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • cetirizine

              buprenorphine, long-acting injection and cetirizine both increase sedation. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate 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.

            • chlordiazepoxide

              chlordiazepoxide 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.

            • chlorothiazide

              buprenorphine, long-acting injection decreases effects of chlorothiazide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • chlorpromazine

              chlorpromazine 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.

            • chlorthalidone

              buprenorphine, long-acting injection decreases effects of chlorthalidone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • chlorzoxazone

              buprenorphine, long-acting injection increases effects of chlorzoxazone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • cisatracurium

              cisatracurium 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.

            • citalopram

              citalopram, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • clarithromycin

              clarithromycin will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • clemastine

              buprenorphine, long-acting injection and clemastine both increase sedation. Use Caution/Monitor.

            • clobazam

              clobazam will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • clomipramine

              clomipramine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • clonazepam

              clonazepam 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.

            • clonidine

              buprenorphine, long-acting injection and clonidine both increase sedation. Use Caution/Monitor.

            • clorazepate

              clorazepate 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.

            • clozapine

              clozapine 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.

              buprenorphine, long-acting injection and clozapine both increase sedation. Use Caution/Monitor.

            • cobicistat

              cobicistat will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • codeine

              codeine 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.

            • conivaptan

              conivaptan will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • crizotinib

              crizotinib will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • cyclobenzaprine

              cyclobenzaprine, buprenorphine, long-acting injection. Either increases toxicity of the other by serum potassium. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

              buprenorphine, long-acting injection increases effects of cyclobenzaprine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • cyclosporine

              cyclosporine will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • cyproheptadine

              buprenorphine, long-acting injection and cyproheptadine both increase sedation. Use Caution/Monitor.

            • dabrafenib

              dabrafenib will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • dantrolene

              buprenorphine, long-acting injection increases effects of dantrolene by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • daridorexant

              buprenorphine, long-acting injection and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • darunavir

              darunavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • desflurane

              desflurane 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.

            • desipramine

              desipramine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • desvenlafaxine

              desvenlafaxine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • dexamethasone

              dexamethasone will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • dexbrompheniramine

              buprenorphine, long-acting injection and dexbrompheniramine both increase sedation. Use Caution/Monitor.

            • dexchlorpheniramine

              buprenorphine, long-acting injection and dexchlorpheniramine both increase sedation. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine 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.

            • dexmethylphenidate

              dexmethylphenidate, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • dextroamphetamine

              dextroamphetamine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • diazepam

              diazepam 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.

              buprenorphine, long-acting injection increases effects of diazepam by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • dicyclomine

              buprenorphine, long-acting injection increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • diethylpropion

              diethylpropion, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • difenoxin hcl

              buprenorphine, long-acting injection and difenoxin hcl both increase sedation. Use Caution/Monitor.

            • diltiazem

              diltiazem will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • dimenhydrinate

              buprenorphine, long-acting injection and dimenhydrinate both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              buprenorphine, long-acting injection and diphenhydramine both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              buprenorphine, long-acting injection and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • doxepin

              doxepin, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • doxycycline

              doxycycline will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • doxylamine

              doxylamine 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.

              buprenorphine, long-acting injection and doxylamine both increase sedation. Use Caution/Monitor.

            • dronedarone

              dronedarone will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • duloxetine

              duloxetine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • efavirenz

              efavirenz will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              buprenorphine, long-acting injection and efavirenz both increase sedation. Use Caution/Monitor.

            • elagolix

              elagolix will decrease the level or effect of buprenorphine, long-acting injection 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 will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • entacapone

              buprenorphine, long-acting injection and entacapone both increase sedation. Use Caution/Monitor.

            • enzalutamide

              enzalutamide will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • erythromycin base

              erythromycin base will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • escitalopram

              escitalopram, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • estazolam

              estazolam 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.

            • eszopiclone

              eszopiclone 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.

              buprenorphine, long-acting injection and eszopiclone both increase sedation. Use Caution/Monitor.

            • ethacrynic acid

              buprenorphine, long-acting injection decreases effects of ethacrynic acid by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • ethanol

              ethanol 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.

              buprenorphine, long-acting injection and ethanol both increase sedation. Use Caution/Monitor.

            • ethosuximide

              buprenorphine, long-acting injection and ethosuximide both increase sedation. Use Caution/Monitor.

            • ethotoin

              buprenorphine, long-acting injection and ethotoin both increase sedation. Use Caution/Monitor.

            • etomidate

              etomidate 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.

            • etravirine

              etravirine will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • felbamate

              buprenorphine, long-acting injection and felbamate both increase sedation. Use Caution/Monitor.

            • fenfluramine

              buprenorphine, long-acting injection and fenfluramine both increase sedation. Use Caution/Monitor.

            • fentanyl

              fentanyl 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.

            • fentanyl intranasal

              fentanyl intranasal 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.

            • fentanyl transdermal

              fentanyl transdermal 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.

            • fentanyl transmucosal

              fentanyl transmucosal 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.

            • fexofenadine

              buprenorphine, long-acting injection and fexofenadine both increase sedation. Use Caution/Monitor.

            • flibanserin

              buprenorphine, long-acting injection and flibanserin both increase sedation. Use Caution/Monitor.

            • fluconazole

              fluconazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • fluoxetine

              fluoxetine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • fluphenazine

              fluphenazine 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.

              buprenorphine, long-acting injection and fluphenazine both increase QTc interval. Use Caution/Monitor.

              buprenorphine, long-acting injection and fluphenazine both increase sedation. Use Caution/Monitor.

            • flurazepam

              flurazepam 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.

            • fluvoxamine

              fluvoxamine and buprenorphine, long-acting injection both increase serotonin levels. Use Caution/Monitor. If concomitant use warranted, carefully observe patient, particularly during treatment initiation, and during dose adjustment of serotonergic drug. Discontinue buprenorphine if serotonin syndrome suspected

            • fosamprenavir

              fosamprenavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • fosaprepitant

              fosaprepitant will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • furosemide

              buprenorphine, long-acting injection decreases effects of furosemide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • gabapentin

              gabapentin, buprenorphine, long-acting injection. 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, long-acting injection. 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.

            • ganaxolone

              buprenorphine, long-acting injection and ganaxolone both increase sedation. Use Caution/Monitor.

            • glycopyrrolate

              buprenorphine, long-acting injection increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • grapefruit

              grapefruit will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • guanfacine

              buprenorphine, long-acting injection and guanfacine both increase sedation. Use Caution/Monitor.

            • haloperidol

              haloperidol will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              haloperidol 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.

              buprenorphine, long-acting injection and haloperidol both increase sedation. Use Caution/Monitor.

            • hydrochlorothiazide

              buprenorphine, long-acting injection decreases effects of hydrochlorothiazide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • hydromorphone

              hydromorphone 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.

            • hydroxyzine

              buprenorphine, long-acting injection and hydroxyzine both increase QTc interval. Modify Therapy/Monitor Closely. If coadministration necessary, consider consider dose reduction of one or both drugs due to potential for additive pharmacological effects

            • hyoscyamine

              buprenorphine, long-acting injection increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • hyoscyamine spray

              buprenorphine, long-acting injection increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • idelalisib

              idelalisib will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • iloperidone

              iloperidone will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              iloperidone 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.

              buprenorphine, long-acting injection and iloperidone both increase sedation. Use Caution/Monitor.

            • imatinib

              imatinib will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • imipramine

              imipramine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • indapamide

              buprenorphine, long-acting injection decreases effects of indapamide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • indinavir

              indinavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • isocarboxazid

              isocarboxazid, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • isoflurane

              isoflurane 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.

            • isoniazid

              isoniazid will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • istradefylline

              istradefylline will increase the level or effect of buprenorphine, long-acting injection 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.

            • itraconazole

              itraconazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • ketamine

              ketamine 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.

              buprenorphine, long-acting injection and ketamine both increase sedation. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • ketotifen, drug-eluting contact lens

              buprenorphine, long-acting injection and ketotifen, drug-eluting contact lens both increase sedation. Use Caution/Monitor.

            • lamotrigine

              buprenorphine, long-acting injection and lamotrigine both increase sedation. Use Caution/Monitor.

            • lapatinib

              lapatinib will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • lasmiditan

              lasmiditan, buprenorphine, long-acting injection. 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, long-acting injection. 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.

            • lenacapavir

              lenacapavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. When initiating buprenorphine while on lenacapavir, use lowest feasible initial or maintenance dose of buprenorphine and carefully titrate dose to desired effect. When initiating lenacapavir while taking buprenorphine, consider adjusting dose for buprenorphine. Monitor clinical signs and symptoms.

            • levetiracetam

              buprenorphine, long-acting injection and levetiracetam both increase sedation. Use Caution/Monitor.

            • levocetirizine

              buprenorphine, long-acting injection and levocetirizine both increase sedation. Use Caution/Monitor.

            • levoketoconazole

              levoketoconazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • levomilnacipran

              levomilnacipran, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • levorphanol

              levorphanol 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.

              buprenorphine, long-acting injection and levorphanol both increase sedation. Use Caution/Monitor.

            • linezolid

              linezolid, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • lisdexamfetamine

              lisdexamfetamine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • lopinavir

              lopinavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • loratadine

              buprenorphine, long-acting injection and loratadine both increase sedation. Use Caution/Monitor.

            • lorazepam

              lorazepam 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.

            • loxapine

              loxapine 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.

              buprenorphine, long-acting injection and loxapine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              loxapine inhaled 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.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • lumateperone

              buprenorphine, long-acting injection and lumateperone both increase sedation. Use Caution/Monitor.

            • lurasidone

              lurasidone 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.

              buprenorphine, long-acting injection and lurasidone both increase sedation. Use Caution/Monitor.

            • maprotiline

              maprotiline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

              buprenorphine, long-acting injection and maprotiline both increase QTc interval. Use Caution/Monitor.

            • meclizine

              buprenorphine, long-acting injection and meclizine both increase sedation. Use Caution/Monitor.

            • meperidine

              meperidine 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.

              buprenorphine, long-acting injection and meperidine both increase sedation. Use Caution/Monitor.

            • meprobamate

              meprobamate 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.

              buprenorphine, long-acting injection and meprobamate both increase sedation. Use Caution/Monitor.

            • metaxalone

              buprenorphine, long-acting injection increases effects of metaxalone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • methadone

              methadone 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.

            • methamphetamine

              methamphetamine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • methocarbamol

              buprenorphine, long-acting injection increases effects of methocarbamol by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • methohexital

              methohexital 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.

            • methscopolamine

              buprenorphine, long-acting injection increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • methsuximide

              buprenorphine, long-acting injection and methsuximide both increase sedation. Use Caution/Monitor.

            • methyclothiazide

              buprenorphine, long-acting injection decreases effects of methyclothiazide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • methylene blue

              methylene blue, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • metolazone

              buprenorphine, long-acting injection decreases effects of metolazone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • metronidazole

              metronidazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • midazolam

              midazolam 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.

            • midazolam intranasal

              midazolam intranasal, buprenorphine, long-acting injection. 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.

            • milnacipran

              milnacipran, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • mirtazapine

              mirtazapine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • mitotane

              mitotane will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • molindone

              molindone 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.

              buprenorphine, long-acting injection and molindone both increase sedation. Use Caution/Monitor.

            • morphine

              morphine 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.

            • nafcillin

              nafcillin will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • nalbuphine

              nalbuphine 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.

            • nefazodone

              nefazodone will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              nefazodone, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • nelfinavir

              nelfinavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • netupitant/palonosetron

              netupitant/palonosetron will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • nevirapine

              nevirapine will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • nicardipine

              nicardipine will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • nitrous oxide

              buprenorphine, long-acting injection and nitrous oxide both increase sedation. Use Caution/Monitor.

            • nortriptyline

              nortriptyline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • olanzapine

              olanzapine 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.

              buprenorphine, long-acting injection and olanzapine both increase sedation. Use Caution/Monitor.

            • opicapone

              buprenorphine, long-acting injection and opicapone both increase sedation. Use Caution/Monitor.

            • opium tincture

              buprenorphine, long-acting injection and opium tincture both increase sedation. Use Caution/Monitor.

            • orphenadrine

              buprenorphine, long-acting injection increases effects of orphenadrine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk for respiratory depression. Monitor for signs of respiratory depression that may be greater than otherwise expected and decrease muscle relaxant dosage as necessary.

            • oxazepam

              oxazepam 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.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • oxycodone

              oxycodone 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.

            • oxymorphone

              oxymorphone 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.

            • paliperidone

              paliperidone 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.

              buprenorphine, long-acting injection and paliperidone both increase sedation. Use Caution/Monitor.

            • pancuronium

              pancuronium 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.

            • paroxetine

              paroxetine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

              buprenorphine, long-acting injection and paroxetine both increase QTc interval. Use Caution/Monitor.

            • pentazocine

              pentazocine 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.

            • pentobarbital

              pentobarbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              pentobarbital 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.

            • perampanel

              buprenorphine, long-acting injection and perampanel both increase sedation. Use Caution/Monitor.

            • perphenazine

              perphenazine 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.

              buprenorphine, long-acting injection and perphenazine both increase QTc interval. Use Caution/Monitor.

              buprenorphine, long-acting injection and perphenazine both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              phendimetrazine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • phenelzine

              phenelzine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • phenobarbital

              phenobarbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • phenytoin

              phenytoin will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • pimavanserin

              pimavanserin 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.

            • pimozide

              pimozide 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.

              buprenorphine, long-acting injection and pimozide both increase sedation. Use Caution/Monitor.

            • pomalidomide

              buprenorphine, long-acting injection and pomalidomide both increase sedation. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • pregabalin

              pregabalin, buprenorphine, long-acting injection. 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 will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              buprenorphine, long-acting injection and primidone both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              prochlorperazine 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.

              buprenorphine, long-acting injection and prochlorperazine both decrease QTc interval. Use Caution/Monitor.

            • propantheline

              buprenorphine, long-acting injection increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • propofol

              propofol 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.

            • protriptyline

              protriptyline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • pyrilamine

              buprenorphine, long-acting injection and pyrilamine both increase sedation. Use Caution/Monitor.

            • quazepam

              quazepam 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.

            • quetiapine

              quetiapine 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.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • ramelteon

              ramelteon 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.

              buprenorphine, long-acting injection and ramelteon both increase sedation. Use Caution/Monitor.

            • ranolazine

              buprenorphine, long-acting injection and ranolazine both increase QTc interval. Use Caution/Monitor.

            • rasagiline

              rasagiline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • remifentanil

              remifentanil 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.

              buprenorphine, long-acting injection and remifentanil both increase sedation. Use Caution/Monitor.

            • reserpine

              buprenorphine, long-acting injection and reserpine both increase sedation. Use Caution/Monitor.

            • ribociclib

              ribociclib will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • rifabutin

              rifabutin will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • rifampin

              rifampin will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • rifapentine

              rifapentine will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • risperidone

              risperidone 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.

              buprenorphine, long-acting injection and risperidone both increase sedation. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • rocuronium

              rocuronium 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.

            • rucaparib

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

            • safinamide

              safinamide, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • saquinavir

              saquinavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • schisandra

              schisandra will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • secobarbital

              secobarbital will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              secobarbital 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.

            • selegiline

              selegiline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • selegiline transdermal

              selegiline transdermal, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • serdexmethylphenidate/dexmethylphenidate

              serdexmethylphenidate/dexmethylphenidate, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • sertraline

              sertraline will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

              sertraline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • sevoflurane

              sevoflurane 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.

            • sodium oxybate

              buprenorphine, long-acting injection and sodium oxybate both increase sedation. Use Caution/Monitor.

            • spironolactone

              buprenorphine, long-acting injection decreases effects of spironolactone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • St John's Wort

              St John's Wort will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • stiripentol

              stiripentol, buprenorphine, long-acting injection. 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.

              buprenorphine, long-acting injection and stiripentol both increase sedation. Use Caution/Monitor.

            • succinylcholine

              succinylcholine 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.

            • sufentanil

              sufentanil 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.

              buprenorphine, long-acting injection and sufentanil both increase sedation. Use Caution/Monitor.

            • sufentanil SL

              sufentanil SL 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.

              buprenorphine, long-acting injection and sufentanil SL both increase sedation. Use Caution/Monitor.

            • suvorexant

              suvorexant 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.

              buprenorphine, long-acting injection and suvorexant both increase sedation. Use Caution/Monitor.

            • tapentadol

              tapentadol 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.

            • tasimelteon

              tasimelteon 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.

              buprenorphine, long-acting injection and tasimelteon both increase sedation. Use Caution/Monitor.

            • tazemetostat

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

            • tecovirimat

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

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inducers should be monitored to ensure buprenorphine plasma levels are adequate. If the buprenorphine dose is inadequate and the CYP3A4 inducer cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • temazepam

              temazepam 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.

            • tetracycline

              tetracycline will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • thioridazine

              thioridazine 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.

            • thiothixene

              thiothixene 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.

              buprenorphine, long-acting injection and thiothixene both increase sedation. Use Caution/Monitor.

            • tiagabine

              buprenorphine, long-acting injection and tiagabine both increase sedation. Use Caution/Monitor.

            • tipranavir

              tipranavir will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • tolcapone

              buprenorphine, long-acting injection and tolcapone both increase sedation. Use Caution/Monitor.

            • topiramate

              buprenorphine, long-acting injection and topiramate both increase sedation. Use Caution/Monitor.

            • torsemide

              buprenorphine, long-acting injection decreases effects of torsemide by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • tramadol

              tramadol 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.

            • tranylcypromine

              tranylcypromine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. Concomitant use could result in life-threatening serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Buprenorphine long-acting injection is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

            • trazodone

              trazodone, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

              buprenorphine, long-acting injection and trazodone both increase sedation. Use Caution/Monitor.

            • triamterene

              buprenorphine, long-acting injection decreases effects of triamterene by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

            • triazolam

              triazolam 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.

            • trifluoperazine

              trifluoperazine 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.

              buprenorphine, long-acting injection and trifluoperazine both decrease QTc interval. Use Caution/Monitor.

              buprenorphine, long-acting injection and trifluoperazine both increase sedation. Use Caution/Monitor.

            • trimipramine

              trimipramine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • triprolidine

              buprenorphine, long-acting injection and triprolidine both increase sedation. Use Caution/Monitor.

            • valproic acid

              buprenorphine, long-acting injection and valproic acid both increase sedation. Use Caution/Monitor.

            • vecuronium

              vecuronium 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.

            • venlafaxine

              venlafaxine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

            • verapamil

              verapamil will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • vigabatrin

              buprenorphine, long-acting injection and vigabatrin both increase sedation. Use Caution/Monitor.

            • voriconazole

              voriconazole will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • zaleplon

              zaleplon 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.

              buprenorphine, long-acting injection and zaleplon both increase sedation. Use Caution/Monitor.

            • ziconotide

              buprenorphine, long-acting injection and ziconotide both increase sedation. Use Caution/Monitor.

            • ziprasidone

              ziprasidone 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.

              buprenorphine, long-acting injection and ziprasidone both increase sedation. Use Caution/Monitor.

            • zolpidem

              zolpidem 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.

              buprenorphine, long-acting injection and zolpidem both increase sedation. Use Caution/Monitor.

            • zonisamide

              buprenorphine, long-acting injection and zonisamide both increase sedation. Use Caution/Monitor.

            Minor (0)

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              Adverse Effects

              >10%

              Sublocade

              • Injection site reactions (5.3-11.6%)

              1-10%

              Sublocade

              • Headache (8.5-9.4%)
              • Constipation (8-9.4%)
              • Vomiting (5.5-9.4%)
              • Nausea (8-8.9%)
              • Fatigue (3.9-6%)
              • CPK increased (2.5-5.4%)
              • ALT increased (1-5%)
              • Somnolence (2-4.9%)
              • AST increased (3.4-4.5%)
              • GGT increased (3-4%)
              • Sedation (1.5-3.4%)
              • Dizziness (1.5-2.5%)

              Brixadi

              • Injection site pain (9.9%)
              • Constipation (7.5%)
              • Headache (7.5%)
              • Nausea (7%)
              • Injection site erythema (6.6%)
              • Injection site pruritus (6.1%)
              • Insomnia (5.6%)
              • Urinary tract infection (5.2%)
              • Injection site swelling (4.7%)
              • Upper respiratory tract infection (4.2%)
              • Injection site reaction (4.2%)
              • Vomiting (4.2%)
              • Arthralgia (3.3%)
              • Diarrhea (2.8%)
              • Anxiety (2.8%)
              • Tachycardia (2.3%)

              Postmarketing Reports

              Serotonin syndrome during concomitant use of opioids with serotonergic drugs

              Adrenal insufficiency with use >1 month

              Anaphylaxis

              Androgen deficiency with long-term opioid use

              Injection site mass, abscess, ulceration, and necrosis

              Insufficient dosing

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              Warnings

              Black Box Warnings

              Serious harm or death resulting from IV administration

              • For subcutaneous (SC) injection only
              • Serious harm or death could result if administered intravenously (IV)
              • The drug forms a solid mass upon contact with body fluids and may cause occlusion, local tissue damage, and thromboembolic events, including life-threatening pulmonary emboli, if administered IV instead of SC
              • The long-acting delivery is achieved by biodegradable depots that are designed to deliver buprenorphine at a controlled rate over a 2-week or 1-month period (depending on the formulation)

              Sublocade REMS program

              • Because of the risk of serious harm or death that could result from IV self-administration, only available through restricted programs (risk evaluation and mitigation strategy [REMS] program)
              • Healthcare settings and pharmacies that order and dispense burenorphine long-acting injection must be certified in this program and comply with the REMS requirements
              • Further information available at
                • www.SublocadeREMS.com or call 1-866-258-3905, OR
                • www.BRIXADIREMS.com or call 1-833-274-9234
              • REMS requirements
                • Healthcare settings and pharmacies that order and dispense must be certified in the REMS program
                • Certified healthcare settings and pharmacies must establish processes and procedures to verify buprenorphine is provided directly to a healthcare provider for administration by a healthcare provider, and the drug is not dispensed to the patient
                • Certified healthcare settings and pharmacies must not distribute, transfer, loan, or sell buprenorphine

              Contraindications

              Documented hypersensitivity to buprenorphine or delivery system components

              Cautions

              Risk of serious harm or death with IV administration (see Black Box Warnings)

              Only available through a restricted access programs (REMS) program (see Black Box Warnings)

              Buprenorphine is a schedule III controlled substance that can be abused in a manner similar to other opioids

              Neonatal withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy, whether that use is medically authorized or illicit; unlike opioid withdrawal syndrome in adults, NOWS may be life-threatening if not recognized and treated in the neonate (also see Pregnancy)

              Adrenal insufficiency reported with opioid use, more often with use exceeding 1 month; if diagnosed, treat with physiologic replacement doses of corticosteroids and wean patient off the opioid to allow adrenal recovery

              Hypersensitivity reported and may include angioneurotic edema and anaphylactic shock; common signs and symptoms include rashes, hives, and pruritus (see Contraindications)

              Because of the partial opioid agonist properties of buprenorphine, it may precipitate opioid withdrawal signs and symptoms in persons who are currently physically dependent on full opioid agonists (eg, heroin, morphine, methadone) before the effects of the full opioid agonist have subsided

              Treat emergent acute pain with a nonopioid analgesic whenever possible; patients requiring opioid therapy for analgesia may be treated with a high–affinity full opioid analgesic under the supervision of a physician, with particular attention to respiratory function; higher doses may be required for analgesic effect

              Deaths reported if used in opioid-naïve individuals who received a 2 mg-dose as a sublingual tablet

              Prolonged QTc interval observed in some patients participating in clinical trials; consider these observations in clinical decisions when prescribing buprenorphine to patients with hypokalemia, hypomagnesemia, or clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia; avoid the use of buprenorphine in patients with a history of long QT syndrome or an immediate family member with this condition or those taking class IA antiarrhythmic medications

              May impair mental or physical abilities; caution patients regarding driving or operating machinery

              Orthostatic hypotension may occur

              May elevate CSF pressure; caution with head injury, intracranial lesions, and other circumstances when CSF pressure may be increased; buprenorphine can produce miosis and changes in the level of consciousness that may interfere with patient evaluation

              Opioids increase intracholedochal pressure; caution with biliary tract dysfunction

              May obscure the diagnosis or clinical course of acute abdominal conditions

              Can cause severe, possibly fatal, respiratory depression in children who are accidentally exposed

              Monitor patients who elect to discontinue treatment for withdrawal signs and symptoms; consider transmucosal buprenorphine if needed to treat withdrawal after discontinuing long-acting injection

              Serious injection-site reactions reported; site reactions are most commonly manifested by pain, erythema, and pruritus; some reports have involved abscess, ulceration, and necrosis; some cases have resulted in surgical depot removal, debridement, antibiotic administration, and therapy discontinuation; likelihood of serious injection site reactions may be increased with inadvertent intramuscular or intradermal administration

              QTc prolongation

              • Thorough QT studies with buprenorphine products have demonstrated QT prolongation less than or equal to 15 msec; this QTc prolongation effect does not appear to be mediated by hERG channels; based on these findings, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors; the risk of combining with other QT-prolonging agents is not known
              • Consider these observations in clinical decisions when prescribing this medication to patients with risk factors such as hypokalemia, bradycardia, recent conversion from atrial fibrillation, congestive heart failure, digitalis therapy, baseline QT prolongation, subclinical long-QT syndrome, or severe hypomagnesemia

              Risk of opioid withdrawal

              • Buprenorphine is a partial agonist at the mu-opioid receptor and long-term administration produces physical dependence of the opioid type, characterized by withdrawal signs and symptoms upon abrupt discontinuation
              • Withdrawal syndrome is milder than that seen with full agonists and may be delayed in onset
              • Owing to the long half-life of buprenorphine long-acting SC injection, withdrawal signs and symptoms emerge after about 1 month following discontinuation

              Hepatitis and hepatic events

              • Cytolytic hepatitis and hepatitis with jaundice reported
              • Abnormalities range from transient asymptomatic elevations in hepatic transaminases to case reports of death, hepatic failure, hepatic necrosis, hepatorenal syndrome, and hepatic encephalopathy
              • Liver function tests, prior to initiation of treatment, are recommended to establish a baseline
              • Monthly monitoring of liver function during treatment, particularly with the 300-mg maintenance dose, is also recommended
              • In a pharmacokinetic study with transmucosal buprenorphine, buprenorphine plasma levels were found to be higher and the half-life was found to be longer in subjects with moderate and severe hepatic impairment, but not in subjects with mild hepatic impairment

              Respiratory depression

              • Associated with life-threatening respiratory depression and death; many, but not all, postmarketing reports regarding coma and death involved misuse by self–injection or were associated with the concomitant use of buprenorphine and benzodiazepines or other CNS depressants, including alcohol; if concomitant use with benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
              • 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
              • Caution with compromised respiratory function (eg, COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, preexisting respiratory depression)
              • Owing to its extended–release characteristics, if discontinued as a result of compromised respiratory function, monitor patients for ongoing buprenorphine effects for several months

              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

              Drug interaction overview

              • Muscle relaxants: Buprenorphine may enhance the neuromuscular blocking action of skeletal muscle relaxants and increase risk of respiratory depression; 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
              • Diuretics: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone
              • Anticholinergics: Coadministration may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus
              • Medications that prolong QT interval (eg, Class IA or Class III antiarrhythmic medications: Buprenorphine may enhance the effects of drugs that cause QT prolongation; coadministration may increase the effects
              • Benzodiazepines or other CNS depressants
                • Concomitant use with benzodiazepines or other CNS depressants, including alcohol, increases the risk of adverse reactions including overdose, respiratory depression, profound sedation, and death
                • For patients in buprenorphine treatment, benzodiazepines are not the treatment of choice for anxiety or insomnia
                • 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 a benzodiazepine or other CNS depressant or decreasing to the lowest effect dose may be appropriate
              • Coadministration with CYP3A4 inhibitors or inducers
                • Buprenorphine is metabolized to norbuprenorphine primarily by CYP3A4
                • CYP3A4 inhibitors (eg, azole antifungals, macrolide antibiotics, protease inhibitors [atazanavir, ritonavir], delavirdine) can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects
                • CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, phenobarbital, efavirenz, nevirapine, etravirine) may induce the metabolism of buprenorphine and, therefore, may cause increased clearance of the drug, which could lead to a decrease in buprenorphine plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome
              • Coadministration with serotonergic drugs
                • MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma); do not use buprenorphine while taking MAOIs or within 14 days of stopping MAOIs (eg, phenelzine, tranylcypromine, linezolid)
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              Pregnancy

              Pregnancy

              Data are limited regarding use in pregnancy; 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

              Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes (eg, low birth weight, preterm birth, fetal death)

              Additionally, untreated opioid addiction often results in continued or relapsing illicit opioid use

              Fetal/neonatal adverse reactions

              • Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with buprenorphine
              • Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight
              • Signs of neonatal withdrawal usually occur in the first days after birth
              • The duration and severity of neonatal opioid withdrawal syndrome may vary
              • Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly

              Labor or delivery

              • Opioid-dependent women on buprenorphine maintenance therapy may require additional analgesia during labor
              • As with all opioids, use of buprenorphine prior to delivery may result in respiratory depression in the newborn; closely monitor neonates for signs of respiratory depression
              • An opioid antagonist (eg, naloxone) should be available for reversal of opioid-induced respiratory depression in the neonate

              Animal data

              • In a pre-and postnatal development study in rats, this drug was administered subcutaneously to pregnant animals once during implantation (on GD 7) and once during weaning (on Lactation Day 7); there were no adverse effects on offspring survival, sexual maturation, behavioral assessment, or reproductive performance at up to 300 mg/kg (approximately 15 times the MRHD on an AUC basis)
              • Reduced fetal body weights increased visceral malformations and skeletal malformations were also observed in rats and rabbits at buprenorphine doses equivalent to 38 and 15 times, respectively, MRHD; the skeletal and visceral malformations in rats appear at least partially attributable to buprenorphine; based on animal data, advise pregnant women of potential risk to fetus

              Lactation

              Based on two studies in 13 lactating women maintained on buprenorphine treatment, buprenorphine and its metabolite norbuprenorphine are present in low levels in human milk and infant urine

              Available data have not shown adverse reactions in breastfed infants, although caution is advised

              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

              Partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor

              Absorption

              Peak plasma time: 24 hr

              Steady-state plasma concentrations

              • Steady-state is reached after 4 injections of 100 mg or 300 mg, or 2 injections of 300 mg
              • Peak plasma concentration: 4.88 ng/mL (100 mg/dose); 10.12 ng/mL (300 mg/dose)
              • Minimum plasma concentration: 2.48 ng/mL (100 mg/dose); 5.01 ng/mL (300 mg/dose)
              • Average plasma concentration (steady-state): 3.21 ng/mL (100 mg/dose); 6.54 ng/mL (300 mg/dose)

              Distribution

              Protein bound: 96%, primarily to alpha and beta globulin

              Metabolism

              Metabolized to its major metabolite, norbuprenorphine, by CYP3A4

              Norbuprenorphine can further undergo glucuronidation

              Elimination

              Half-life: 43-60 days

              Excretion: 30% (<1% unchanged) urine; 69% (33% unchanged) feces

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              Administration

              Drug addiction treatment act

              Under the Drug Addiction Treatment Act (DATA) codified at 21 U.S.C. 823(g), prescription use of this product in treatment of opioid dependence is limited to healthcare providers who meet certain qualifying requirements, and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe this product for the treatment of opioid dependence and have been assigned a unique identification number that must be included on every prescription

              SC Preparation

              Only healthcare providers should prepare and administer

              As a universal precaution, always wear gloves

              Sublocade: Remove buprenorphine long-acting SC injection from refrigerator before administration; requires at least 15 minutes to reach room temperature

              Wait until the patient has arrived for his or her injection; do not open package and do not attach needle until time of injection

              Administer each injection only using the syringe and safety needle included with the product

              SC Administration

              For SC injection only; do not administer IV or IM

              Subcutaneous tissue should be free of skin conditions (eg, nodules, lesions, excessive pigment); not for injection into an area where skin is irritated, reddened, bruised, infected or scarred in any way

              Place patient in supine position

              Sublocade

              • Choose an injection site on the abdomen between the transpyloric and transtubercular planes with adequate subcutaneous tissue
              • Rotate injection sites

              Brixadi

              • Injected slowly, into subcutaneous tissue of buttock, thigh, abdomen, or upper arm
              • Rotate injection sites
              • Administer as a single injection, do not divide
              • Weekly doses cannot be combined to yield a monthly dose

              Missed or delayed doses

              • Sublocade
                • A patient who misses a dose should receive the next dose as soon as possible, with the following dose given no sooner than 26 days later
                • Occasional delays in dosing up to 2 weeks are not expected to have a clinically significant impact on treatment effect
              • Brixadi weekly
                • Administer q7days; to avoid missed doses, the weekly dose may be administered up to 2 days before or after the weekly time point
              • Brixadi monthly
                • Administer q28days; to avoid missed doses, the monthly dose may be administered up to 1 week before or after the monthly time point

              Storage

              Sublocade

              • Refrigerate at 2-8°C (35.6-46.4°F)
              • Once outside the refrigerator, this product may be stored in its original packaging at room temperature at 15-30°C (59-86°F) for up to 7 days prior to administration
              • Discard if left at room temperature >7 days

              Brixadi

              • Store at room temperature at 20-25ºC (68-77ºF); with excursions permitted at 15-30ºC (59-86ºF)
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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.
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              • 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.