buprenorphine subdermal implant (Rx)

Opioid Addiction

Indicated for the maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine-containing product (ie, doses ≤8 mg/day of Subutex or Suboxone sublingual tablet equivalent or generic equivalent)

4 implants (80 mg/implant of buprenorphine HCl) are inserted in the upper arm for 6 months of treatment and removed by the end of the sixth month (see Administration)

Dosing Considerations

Only for patients who are opioid tolerant

Part of a complete treatment program to include counseling and psychosocial support

Not appropriate for new entrant to treatment and patients who have not achieved and sustained prolonged clinical stability while being maintained on buprenorphine ≤8 mg/day

May only be prescribed by physicians who have met qualifying requirements and who have notified the Secretary of Health and Human Services (HHS) of their intent to prescribe or dispense this product for the treatment of opioid dependence

All healthcare providers who intend to prescribe and/or perform insertions/removals must successfully complete a live training program and demonstrate procedural competency

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)

<16 years: Safety and efficacy not established

Contraindicated (4)

• dronedarone

  buprenorphine subdermal implant and dronedarone both increase QTc interval. Contraindicated.

• lefamulin

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

• posaconazole

  buprenorphine subdermal implant and posaconazole both increase QTc interval. Contraindicated.

• thioridazine

  buprenorphine subdermal implant and thioridazine both increase QTc interval. Contraindicated.

Serious - Use Alternative (156)

• abametapir

  abametapir will increase the level or effect of buprenorphine subdermal implant 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.

• amiodarone

  buprenorphine subdermal implant and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  buprenorphine subdermal implant and amisulpride both increase QTc interval. Avoid or Use Alternate Drug.

• amitriptyline

  buprenorphine subdermal implant and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• amoxapine

  buprenorphine subdermal implant and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.

• anagrelide

  buprenorphine subdermal implant and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

• apalutamide

  apalutamide will decrease the level or effect of buprenorphine subdermal implant 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 subdermal implant and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

• aripiprazole

  buprenorphine subdermal implant and aripiprazole both increase QTc interval. Avoid or Use Alternate Drug.

• arsenic trioxide

  buprenorphine subdermal implant and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  buprenorphine subdermal implant and artemether both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  buprenorphine subdermal implant and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• asenapine

  buprenorphine subdermal implant and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• atomoxetine

  buprenorphine subdermal implant and atomoxetine both increase QTc interval. Avoid or Use Alternate Drug.

• azithromycin

  buprenorphine subdermal implant and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• bedaquiline

  buprenorphine subdermal implant and bedaquiline both increase QTc interval. Avoid or Use Alternate Drug.

• benzhydrocodone/acetaminophen

  buprenorphine subdermal implant 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.

• ceritinib

  buprenorphine subdermal implant and ceritinib both increase QTc interval. Avoid or Use Alternate Drug.

• chloroquine

  buprenorphine subdermal implant and chloroquine both increase QTc interval. Avoid or Use Alternate Drug.

• chlorpromazine

  buprenorphine subdermal implant and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

• ciprofloxacin

  buprenorphine subdermal implant and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• citalopram

  buprenorphine subdermal implant and citalopram both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  buprenorphine subdermal implant and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clomipramine

  buprenorphine subdermal implant and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.

• clonidine

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

• clozapine

  buprenorphine subdermal implant and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• crizotinib

  buprenorphine subdermal implant and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

• dasatinib

  buprenorphine subdermal implant and dasatinib both increase QTc interval. Avoid or Use Alternate Drug.

• degarelix

  buprenorphine subdermal implant and degarelix both increase QTc interval. Avoid or Use Alternate Drug.

• desflurane

  buprenorphine subdermal implant and desflurane both increase QTc interval. Avoid or Use Alternate Drug.

• desipramine

  buprenorphine subdermal implant and desipramine both increase QTc interval. Avoid or Use Alternate Drug.

• deutetrabenazine

  buprenorphine subdermal implant and deutetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

• diazepam intranasal

  diazepam intranasal, buprenorphine subdermal implant. 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 subdermal implant and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

• dofetilide

  buprenorphine subdermal implant and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  buprenorphine subdermal implant and dolasetron both increase QTc interval. Avoid or Use Alternate Drug.

• donepezil

  buprenorphine subdermal implant and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

• doxepin

  buprenorphine subdermal implant and doxepin both increase QTc interval. Avoid or Use Alternate Drug.

• efavirenz

  buprenorphine subdermal implant and efavirenz both increase QTc interval. Avoid or Use Alternate Drug.

• eliglustat

  buprenorphine subdermal implant and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.

• encorafenib

  buprenorphine subdermal implant and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  buprenorphine subdermal implant and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

• eribulin

  buprenorphine subdermal implant and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin base

  buprenorphine subdermal implant and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  buprenorphine subdermal implant and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  buprenorphine subdermal implant and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  buprenorphine subdermal implant and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  buprenorphine subdermal implant and escitalopram both increase QTc interval. Avoid or Use Alternate Drug.

• fexinidazole

  fexinidazole will increase the level or effect of buprenorphine subdermal implant 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 subdermal implant and fexinidazole both increase QTc interval. Avoid or Use Alternate Drug.

• fingolimod

  buprenorphine subdermal implant and fingolimod both increase QTc interval. Avoid or Use Alternate Drug.

• flecainide

  buprenorphine subdermal implant and flecainide both increase QTc interval. Avoid or Use Alternate Drug.

• fluconazole

  buprenorphine subdermal implant and fluconazole both increase QTc interval. Contraindicated.

• fluoxetine

  buprenorphine subdermal implant and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug.

• fluvoxamine

  buprenorphine subdermal implant and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug.

• foscarnet

  buprenorphine subdermal implant and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

• fostemsavir

  buprenorphine subdermal implant and fostemsavir both increase QTc interval. Avoid or Use Alternate Drug.

• gemifloxacin

  buprenorphine subdermal implant and gemifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• gemtuzumab

  buprenorphine subdermal implant and gemtuzumab both increase QTc interval. Avoid or Use Alternate Drug.

• gilteritinib

  buprenorphine subdermal implant and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.

• glasdegib

  buprenorphine subdermal implant and glasdegib both increase QTc interval. Avoid or Use Alternate Drug.

• goserelin

  buprenorphine subdermal implant and goserelin both increase QTc interval. Avoid or Use Alternate Drug.

• granisetron

  buprenorphine subdermal implant and granisetron both increase QTc interval. Avoid or Use Alternate Drug.

• haloperidol

  buprenorphine subdermal implant and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

• histrelin

  buprenorphine subdermal implant and histrelin both increase QTc interval. Avoid or Use Alternate Drug.

• hydrocodone

  buprenorphine subdermal implant 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. .

• hydroxychloroquine sulfate

  buprenorphine subdermal implant and hydroxychloroquine sulfate both increase QTc interval. Avoid or Use Alternate Drug.

• ibutilide

  buprenorphine subdermal implant and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

• iloperidone

  buprenorphine subdermal implant and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

• imipramine

  buprenorphine subdermal implant and imipramine both increase QTc interval. Avoid or Use Alternate Drug.

• inotuzumab

  buprenorphine subdermal implant and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.

• isoflurane

  buprenorphine subdermal implant and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.

• itraconazole

  buprenorphine subdermal implant and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  ivosidenib will decrease the level or effect of buprenorphine subdermal implant 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 subdermal implant and ivosidenib both decrease QTc interval. Avoid or Use Alternate Drug.

• lapatinib

  buprenorphine subdermal implant and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.

• lefamulin

  buprenorphine subdermal implant and lefamulin both increase QTc interval. Avoid or Use Alternate Drug.

• lenvatinib

  buprenorphine subdermal implant and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.

• leuprolide

  buprenorphine subdermal implant and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.

• levofloxacin

  buprenorphine subdermal implant and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• lithium

  buprenorphine subdermal implant and lithium both increase QTc interval. Avoid or Use Alternate Drug.

• lofexidine

  buprenorphine subdermal implant and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

• lonafarnib

  lonafarnib will increase the level or effect of buprenorphine subdermal implant 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 subdermal implant and loperamide both increase QTc interval. Avoid or Use Alternate Drug.

• lopinavir

  buprenorphine subdermal implant and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

• macimorelin

  buprenorphine subdermal implant and macimorelin both increase QTc interval. Avoid or Use Alternate Drug.

• mefloquine

  buprenorphine subdermal implant and mefloquine both increase QTc interval. Avoid or Use Alternate Drug.

• methadone

  buprenorphine subdermal implant and methadone both increase QTc interval. Avoid or Use Alternate Drug.

• metoclopramide intranasal

  buprenorphine subdermal implant, 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.

• midostaurin

  buprenorphine subdermal implant and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

• mifepristone

  buprenorphine subdermal implant and mifepristone both increase QTc interval. Avoid or Use Alternate Drug.

• mirtazapine

  buprenorphine subdermal implant and mirtazapine both increase QTc interval. Avoid or Use Alternate Drug.

• mobocertinib

  buprenorphine subdermal implant and mobocertinib both increase QTc interval. Avoid or Use Alternate Drug.

• moxifloxacin

  buprenorphine subdermal implant and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• nilotinib

  buprenorphine subdermal implant and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• nortriptyline

  buprenorphine subdermal implant and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide

  buprenorphine subdermal implant and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  buprenorphine subdermal implant and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• olanzapine

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

• olopatadine intranasal

  buprenorphine subdermal implant 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 subdermal implant and ondansetron both increase QTc interval. Avoid or Use Alternate Drug.

• osilodrostat

  buprenorphine subdermal implant 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 subdermal implant and osimertinib both increase QTc interval. Avoid or Use Alternate Drug.

• oxaliplatin

  buprenorphine subdermal implant and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

• ozanimod

  ozanimod and buprenorphine subdermal implant 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 subdermal implant and ozanimod both increase QTc interval. Avoid or Use Alternate Drug.

• paliperidone

  buprenorphine subdermal implant and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

• panobinostat

  buprenorphine subdermal implant and panobinostat both increase QTc interval. Avoid or Use Alternate Drug.

• paroxetine

  buprenorphine subdermal implant and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.

• pasireotide

  buprenorphine subdermal implant and pasireotide both increase QTc interval. Avoid or Use Alternate Drug.

• pazopanib

  buprenorphine subdermal implant and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

• pentamidine

  buprenorphine subdermal implant and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

• pimavanserin

  buprenorphine subdermal implant and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• pimozide

  buprenorphine subdermal implant and pimozide both increase QTc interval. Contraindicated.

• pitolisant

  buprenorphine subdermal implant and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

• ponesimod

  buprenorphine subdermal implant and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

• primaquine

  buprenorphine subdermal implant and primaquine both increase QTc interval. Avoid or Use Alternate Drug.

• procainamide

  buprenorphine subdermal implant and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

• promethazine

  buprenorphine subdermal implant and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• propafenone

  buprenorphine subdermal implant and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

• protriptyline

  buprenorphine subdermal implant and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• quetiapine

  buprenorphine subdermal implant and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.

• quinidine

  buprenorphine subdermal implant and quinidine both increase QTc interval. Avoid or Use Alternate Drug.

• quinine

  buprenorphine subdermal implant and quinine both increase QTc interval. Avoid or Use Alternate Drug.

• ribociclib

  buprenorphine subdermal implant and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

• rilpivirine

  buprenorphine subdermal implant and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

• risperidone

  buprenorphine subdermal implant and risperidone both increase QTc interval. Avoid or Use Alternate Drug.

• romidepsin

  buprenorphine subdermal implant and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

• saquinavir

  buprenorphine subdermal implant and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.

• selinexor

  selinexor, buprenorphine subdermal implant. 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 subdermal implant and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

• sertraline

  buprenorphine subdermal implant and sertraline both increase QTc interval. Avoid or Use Alternate Drug.

• sevoflurane

  buprenorphine subdermal implant and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

• siponimod

  buprenorphine subdermal implant and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

• solifenacin

  buprenorphine subdermal implant and solifenacin both increase QTc interval. Avoid or Use Alternate Drug.

• sorafenib

  buprenorphine subdermal implant and sorafenib both increase QTc interval. Avoid or Use Alternate Drug.

• sotalol

  buprenorphine subdermal implant and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

• sufentanil SL

  buprenorphine subdermal implant 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 subdermal implant and sunitinib both increase QTc interval. Avoid or Use Alternate Drug.

• tacrolimus

  buprenorphine subdermal implant and tacrolimus both increase QTc interval. Avoid or Use Alternate Drug.

• telavancin

  buprenorphine subdermal implant and telavancin both increase QTc interval. Avoid or Use Alternate Drug.

• tetrabenazine

  buprenorphine subdermal implant and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

• toremifene

  buprenorphine subdermal implant and toremifene both increase QTc interval. Avoid or Use Alternate Drug.

• trazodone

  buprenorphine subdermal implant and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

• triclabendazole

  buprenorphine subdermal implant and triclabendazole both increase QTc interval. Avoid or Use Alternate Drug.

• trimipramine

  buprenorphine subdermal implant and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.

• triptorelin

  buprenorphine subdermal implant and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.

• tucatinib

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

• valerian

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

• vandetanib

  buprenorphine subdermal implant and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.

• vardenafil

  buprenorphine subdermal implant and vardenafil both increase QTc interval. Avoid or Use Alternate Drug.

• vemurafenib

  buprenorphine subdermal implant and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.

• venlafaxine

  buprenorphine subdermal implant and venlafaxine both decrease QTc interval. Avoid or Use Alternate Drug.

• voclosporin

  buprenorphine subdermal implant and voclosporin both increase QTc interval. Avoid or Use Alternate Drug.

• voriconazole

  buprenorphine subdermal implant and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.

• vorinostat

  buprenorphine subdermal implant and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.

• voxelotor

  voxelotor will increase the level or effect of buprenorphine subdermal implant 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 subdermal implant and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

Monitor Closely (158)

• albuterol

  buprenorphine subdermal implant and albuterol both increase QTc interval. Use Caution/Monitor.

• alfuzosin

  buprenorphine subdermal implant and alfuzosin both increase QTc interval. Use Caution/Monitor.

• alprazolam

  alprazolam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• amiodarone

  amiodarone will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• amitriptyline

  amitriptyline, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• amoxapine

  amoxapine, buprenorphine subdermal implant. 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 subdermal implant. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. 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 subdermal implant 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• arformoterol

  buprenorphine subdermal implant and arformoterol both increase QTc interval. Use Caution/Monitor.

• armodafinil

  armodafinil will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• atazanavir

  atazanavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• belzutifan

  belzutifan will decrease the level or effect of buprenorphine subdermal implant 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.

• bicalutamide

  bicalutamide will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• bosentan

  bosentan will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• brexanolone

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

• butabarbital

  butabarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• carbamazepine

  carbamazepine decreases levels of buprenorphine subdermal implant by increasing metabolism. Use Caution/Monitor. Carbamazepine increases metabolism of buprenorphine; monitor for decreased efficacy.
  
  carbamazepine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• cenobamate

  cenobamate will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
  
  cenobamate, buprenorphine subdermal implant. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  ceritinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• chlordiazepoxide

  chlordiazepoxide increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• citalopram

  citalopram, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• clobazam

  clobazam will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.
  
  clobazam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• clomipramine

  clomipramine, buprenorphine subdermal implant. 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 subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• clorazepate

  clorazepate increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• cobicistat

  cobicistat will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• conivaptan

  conivaptan will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• crizotinib

  crizotinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• cyclobenzaprine

  cyclobenzaprine, buprenorphine subdermal implant. 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.

• cyclosporine

  cyclosporine will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• dabrafenib

  dabrafenib will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• daridorexant

  buprenorphine subdermal implant 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• desipramine

  desipramine will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.
  
  desipramine, buprenorphine subdermal implant. 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 subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• dexmethylphenidate

  dexmethylphenidate, buprenorphine subdermal implant. 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 subdermal implant. 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 subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• diethylpropion

  diethylpropion, buprenorphine subdermal implant. 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.

• diltiazem

  diltiazem will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• doxepin

  doxepin, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• dronedarone

  dronedarone will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• duloxetine

  duloxetine, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• elagolix

  elagolix will decrease the level or effect of buprenorphine subdermal implant 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.

• encorafenib

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

• enzalutamide

  enzalutamide will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• erythromycin base

  erythromycin base will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of buprenorphine subdermal implant by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• escitalopram

  escitalopram, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• etravirine

  etravirine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• fedratinib

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

• flibanserin

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

• fluconazole

  fluconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• fluoxetine

  fluoxetine, buprenorphine subdermal implant. 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

  buprenorphine subdermal implant and fluphenazine both increase QTc interval. Use Caution/Monitor.

• flurazepam

  flurazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• fluvoxamine

  fluvoxamine and buprenorphine subdermal implant 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• fosaprepitant

  fosaprepitant will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• fosphenytoin

  fosphenytoin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• gabapentin

  gabapentin, buprenorphine subdermal implant. 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 subdermal implant. 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 subdermal implant and ganaxolone both increase sedation. Use Caution/Monitor.

• grapefruit

  grapefruit will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• haloperidol

  haloperidol will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• hydroxyzine

  buprenorphine subdermal implant 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

• idelalisib

  idelalisib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• iloperidone

  iloperidone will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• imatinib

  imatinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• imipramine

  imipramine, buprenorphine subdermal implant. 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.

• indinavir

  indinavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• isocarboxazid

  isocarboxazid, buprenorphine subdermal implant. 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.

• isoniazid

  isoniazid will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• istradefylline

  istradefylline will increase the level or effect of buprenorphine subdermal implant 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• ketoconazole

  ketoconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• lapatinib

  lapatinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• lasmiditan

  lasmiditan, buprenorphine subdermal implant. 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 subdermal implant. 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 subdermal implant 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.

• levoketoconazole

  levoketoconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• levomilnacipran

  levomilnacipran, buprenorphine subdermal implant. 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.

• linezolid

  linezolid, buprenorphine subdermal implant. 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.

• lisdexamfetamine

  lisdexamfetamine, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• lorazepam

  lorazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• maprotiline

  maprotiline, buprenorphine subdermal implant. 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 subdermal implant and maprotiline both increase QTc interval. Use Caution/Monitor.

• methamphetamine

  methamphetamine, buprenorphine subdermal implant. 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.

• methylene blue

  methylene blue, buprenorphine subdermal implant. 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.

• metronidazole

  metronidazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• midazolam

  midazolam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• midazolam intranasal

  midazolam intranasal, buprenorphine subdermal implant. 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 subdermal implant. 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 subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• nafcillin

  nafcillin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• nefazodone

  nefazodone will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.
  
  nefazodone, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• netupitant/palonosetron

  netupitant/palonosetron will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• nevirapine

  nevirapine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• nicardipine

  nicardipine will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• nortriptyline

  nortriptyline, buprenorphine subdermal implant. 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.

• oxazepam

  oxazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• paroxetine

  paroxetine, buprenorphine subdermal implant. 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.

• pentobarbital

  pentobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• perphenazine

  buprenorphine subdermal implant and perphenazine both increase QTc interval. Use Caution/Monitor.

• phendimetrazine

  phendimetrazine, buprenorphine subdermal implant. 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 subdermal implant. 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.

• phenobarbital

  phenobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• phenytoin

  phenytoin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• posaconazole

  posaconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• pregabalin

  pregabalin, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• prochlorperazine

  buprenorphine subdermal implant and prochlorperazine both decrease QTc interval. Use Caution/Monitor.

• protriptyline

  protriptyline, buprenorphine subdermal implant. 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.

• quazepam

  quazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• quinupristin/dalfopristin

  quinupristin/dalfopristin will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• ranolazine

  buprenorphine subdermal implant and ranolazine both increase QTc interval. Use Caution/Monitor.

• rasagiline

  rasagiline, buprenorphine subdermal implant. 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.

• ribociclib

  ribociclib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• rifabutin

  rifabutin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• rifampin

  rifampin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• ritonavir

  ritonavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• rucaparib

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

• safinamide

  safinamide, buprenorphine subdermal implant. 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.

• saquinavir

  saquinavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• schisandra

  schisandra will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• secobarbital

  secobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• selegiline

  selegiline, buprenorphine subdermal implant. 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.

• selegiline transdermal

  selegiline transdermal, buprenorphine subdermal implant. 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.

• serdexmethylphenidate/dexmethylphenidate

  serdexmethylphenidate/dexmethylphenidate, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.
  
  sertraline, buprenorphine subdermal implant. 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.

• St John's Wort

  St John's Wort will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• suvorexant

  suvorexant and buprenorphine subdermal implant both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant may be necessary

• tazemetostat

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

• tecovirimat

  tecovirimat will decrease the level or effect of buprenorphine subdermal implant 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• temazepam

  temazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• tetracycline

  tetracycline will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• tipranavir

  tipranavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• tranylcypromine

  tranylcypromine, buprenorphine subdermal implant. 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.

• trazodone

  trazodone, buprenorphine subdermal implant. 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.

• trifluoperazine

  buprenorphine subdermal implant and trifluoperazine both decrease QTc interval. Use Caution/Monitor.

• trimipramine

  trimipramine, buprenorphine subdermal implant. 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.

• venlafaxine

  venlafaxine, buprenorphine subdermal implant. 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 subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• voriconazole

  voriconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

Minor (2)

• butalbital

  butalbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• rifapentine

  rifapentine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of buprenorphine subdermal implant 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.

• albuterol

  Monitor Closely (1)buprenorphine subdermal implant and albuterol both increase QTc interval. Use Caution/Monitor.

• alfuzosin

  Monitor Closely (1)buprenorphine subdermal implant and alfuzosin both increase QTc interval. Use Caution/Monitor.

• alprazolam

  Monitor Closely (1)alprazolam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  Serious - Use Alternative (1)buprenorphine subdermal implant and amisulpride both increase QTc interval. Avoid or Use Alternate Drug.

• amitriptyline

  Monitor Closely (1)amitriptyline, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• amobarbital

  Monitor Closely (1)amobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• amoxapine

  Monitor Closely (1)amoxapine, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.

• amphetamine polistirex

  Monitor Closely (1)amphetamine polistirex, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Modify Therapy/Monitor Closely. 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.

• anagrelide

  Serious - Use Alternative (1)buprenorphine subdermal implant and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of buprenorphine subdermal implant by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.Serious - Use Alternative (1)apalutamide will decrease the level or effect of buprenorphine subdermal implant 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

  Serious - Use Alternative (1)buprenorphine subdermal implant and apomorphine both increase QTc interval. Avoid or Use Alternate Drug.

• aprepitant

  Monitor Closely (1)aprepitant will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• arformoterol

  Monitor Closely (1)buprenorphine subdermal implant and arformoterol both increase QTc interval. Use Caution/Monitor.

• aripiprazole

  Serious - Use Alternative (1)buprenorphine subdermal implant and aripiprazole both increase QTc interval. Avoid or Use Alternate Drug.

• armodafinil

  Monitor Closely (1)armodafinil will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• arsenic trioxide

  Serious - Use Alternative (1)buprenorphine subdermal implant and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  Serious - Use Alternative (1)buprenorphine subdermal implant and artemether both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Serious - Use Alternative (1)buprenorphine subdermal implant and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• asenapine

  Serious - Use Alternative (1)buprenorphine subdermal implant and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

• atazanavir

  Monitor Closely (1)atazanavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• atomoxetine

  Serious - Use Alternative (1)buprenorphine subdermal implant and atomoxetine both increase QTc interval. Avoid or Use Alternate Drug.

• azithromycin

  Serious - Use Alternative (1)buprenorphine subdermal implant and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• bedaquiline

  Serious - Use Alternative (1)buprenorphine subdermal implant and bedaquiline both increase QTc interval. Avoid or Use Alternate Drug.

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of buprenorphine subdermal implant 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.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (1)buprenorphine subdermal implant 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.

• bicalutamide

  Monitor Closely (1)bicalutamide will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• bosentan

  Monitor Closely (1)bosentan will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• brexanolone

  Monitor Closely (1)brexanolone, buprenorphine subdermal implant. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• butabarbital

  Monitor Closely (1)butabarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• butalbital

  Minor (1)butalbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• carbamazepine

  Monitor Closely (2)carbamazepine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.
  
  carbamazepine decreases levels of buprenorphine subdermal implant by increasing metabolism. Use Caution/Monitor. Carbamazepine increases metabolism of buprenorphine; monitor for decreased efficacy.

• cenobamate

  Monitor Closely (2)cenobamate, buprenorphine subdermal implant. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Monitor Closely (1)ceritinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and ceritinib both increase QTc interval. Avoid or Use Alternate Drug.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• chloroquine

  Serious - Use Alternative (1)buprenorphine subdermal implant and chloroquine both increase QTc interval. Avoid or Use Alternate Drug.

• chlorpromazine

  Serious - Use Alternative (1)buprenorphine subdermal implant and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

• ciprofloxacin

  Serious - Use Alternative (1)buprenorphine subdermal implant and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• citalopram

  Monitor Closely (1)citalopram, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and citalopram both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clobazam

  Monitor Closely (2)clobazam will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.
  
  clobazam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• clomipramine

  Monitor Closely (1)clomipramine, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.

• clonazepam

  Monitor Closely (1)clonazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• clonidine

  Serious - Use Alternative (1)clonidine, buprenorphine subdermal implant. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• clorazepate

  Monitor Closely (1)clorazepate increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• clozapine

  Serious - Use Alternative (1)buprenorphine subdermal implant and clozapine both increase QTc interval. Avoid or Use Alternate Drug.

• cobicistat

  Monitor Closely (1)cobicistat will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• conivaptan

  Monitor Closely (1)conivaptan will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• crizotinib

  Monitor Closely (1)crizotinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

• cyclobenzaprine

  Monitor Closely (1)cyclobenzaprine, buprenorphine subdermal implant. 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.

• cyclosporine

  Monitor Closely (1)cyclosporine will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• daridorexant

  Monitor Closely (1)buprenorphine subdermal implant 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

  Monitor Closely (1)darunavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• dasatinib

  Serious - Use Alternative (1)buprenorphine subdermal implant and dasatinib both increase QTc interval. Avoid or Use Alternate Drug.

• degarelix

  Serious - Use Alternative (1)buprenorphine subdermal implant and degarelix both increase QTc interval. Avoid or Use Alternate Drug.

• desflurane

  Serious - Use Alternative (1)buprenorphine subdermal implant and desflurane both increase QTc interval. Avoid or Use Alternate Drug.

• desipramine

  Monitor Closely (2)desipramine, buprenorphine subdermal implant. 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.
  
  desipramine will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and desipramine both increase QTc interval. Avoid or Use Alternate Drug.

• desvenlafaxine

  Monitor Closely (1)desvenlafaxine, buprenorphine subdermal implant. 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.

• deutetrabenazine

  Serious - Use Alternative (1)buprenorphine subdermal implant and deutetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

• dexamethasone

  Monitor Closely (1)dexamethasone will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• dexmethylphenidate

  Monitor Closely (1)dexmethylphenidate, buprenorphine subdermal implant. 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

  Monitor Closely (1)dextroamphetamine, buprenorphine subdermal implant. 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

  Monitor Closely (1)diazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• diazepam intranasal

  Serious - Use Alternative (1)diazepam intranasal, buprenorphine subdermal implant. 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.

• diethylpropion

  Monitor Closely (1)diethylpropion, buprenorphine subdermal implant. 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.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• disopyramide

  Serious - Use Alternative (1)buprenorphine subdermal implant and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

• dofetilide

  Serious - Use Alternative (1)buprenorphine subdermal implant and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Serious - Use Alternative (1)buprenorphine subdermal implant and dolasetron both increase QTc interval. Avoid or Use Alternate Drug.

• donepezil

  Serious - Use Alternative (1)buprenorphine subdermal implant and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

• doxepin

  Monitor Closely (1)doxepin, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and doxepin both increase QTc interval. Avoid or Use Alternate Drug.

• doxycycline

  Monitor Closely (1)doxycycline will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• dronedarone

  Contraindicated (1)buprenorphine subdermal implant and dronedarone both increase QTc interval. Contraindicated.Monitor Closely (1)dronedarone will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• duloxetine

  Monitor Closely (1)duloxetine, buprenorphine subdermal implant. 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

  Monitor Closely (1)efavirenz will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.Serious - Use Alternative (1)buprenorphine subdermal implant and efavirenz both increase QTc interval. Avoid or Use Alternate Drug.

• elagolix

  Monitor Closely (1)elagolix will decrease the level or effect of buprenorphine subdermal implant 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.

• eliglustat

  Serious - Use Alternative (1)buprenorphine subdermal implant and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.

• encorafenib

  Monitor Closely (1)encorafenib, buprenorphine subdermal implant. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.Serious - Use Alternative (1)buprenorphine subdermal implant and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  Serious - Use Alternative (1)buprenorphine subdermal implant and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

• enzalutamide

  Monitor Closely (1)enzalutamide will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• eribulin

  Serious - Use Alternative (1)buprenorphine subdermal implant and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin base

  Monitor Closely (1)erythromycin base will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Monitor Closely (1)erythromycin ethylsuccinate will increase the level or effect of buprenorphine subdermal implant by affecting hepatic enzyme CYP2E1 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Monitor Closely (1)erythromycin lactobionate will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  Monitor Closely (1)erythromycin stearate will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  Monitor Closely (1)escitalopram, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and escitalopram both increase QTc interval. Avoid or Use Alternate Drug.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• etravirine

  Monitor Closely (1)etravirine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• fexinidazole

  Serious - Use Alternative (2)fexinidazole will increase the level or effect of buprenorphine subdermal implant 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 subdermal implant and fexinidazole both increase QTc interval. Avoid or Use Alternate Drug.

• fingolimod

  Serious - Use Alternative (1)buprenorphine subdermal implant and fingolimod both increase QTc interval. Avoid or Use Alternate Drug.

• flecainide

  Serious - Use Alternative (1)buprenorphine subdermal implant and flecainide both increase QTc interval. Avoid or Use Alternate Drug.

• flibanserin

  Monitor Closely (1)buprenorphine subdermal implant and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluconazole

  Monitor Closely (1)fluconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and fluconazole both increase QTc interval. Contraindicated.

• fluoxetine

  Monitor Closely (1)fluoxetine, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug.

• fluphenazine

  Monitor Closely (1)buprenorphine subdermal implant and fluphenazine both increase QTc interval. Use Caution/Monitor.

• flurazepam

  Monitor Closely (1)flurazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• fluvoxamine

  Monitor Closely (1)fluvoxamine and buprenorphine subdermal implant 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 suspectedSerious - Use Alternative (1)buprenorphine subdermal implant and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug.

• fosamprenavir

  Monitor Closely (1)fosamprenavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• fosaprepitant

  Monitor Closely (1)fosaprepitant will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• foscarnet

  Serious - Use Alternative (1)buprenorphine subdermal implant and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

• fosphenytoin

  Monitor Closely (1)fosphenytoin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• fostemsavir

  Serious - Use Alternative (1)buprenorphine subdermal implant and fostemsavir both increase QTc interval. Avoid or Use Alternate Drug.

• gabapentin

  Monitor Closely (1)gabapentin, buprenorphine subdermal implant. 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

  Monitor Closely (1)gabapentin enacarbil, buprenorphine subdermal implant. 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

  Monitor Closely (1)buprenorphine subdermal implant and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  Serious - Use Alternative (1)buprenorphine subdermal implant and gemifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• gemtuzumab

  Serious - Use Alternative (1)buprenorphine subdermal implant and gemtuzumab both increase QTc interval. Avoid or Use Alternate Drug.

• gilteritinib

  Serious - Use Alternative (1)buprenorphine subdermal implant and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.

• glasdegib

  Serious - Use Alternative (1)buprenorphine subdermal implant and glasdegib both increase QTc interval. Avoid or Use Alternate Drug.

• goserelin

  Serious - Use Alternative (1)buprenorphine subdermal implant and goserelin both increase QTc interval. Avoid or Use Alternate Drug.

• granisetron

  Serious - Use Alternative (1)buprenorphine subdermal implant and granisetron both increase QTc interval. Avoid or Use Alternate Drug.

• grapefruit

  Monitor Closely (1)grapefruit will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• haloperidol

  Monitor Closely (1)haloperidol will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

• histrelin

  Serious - Use Alternative (1)buprenorphine subdermal implant and histrelin both increase QTc interval. Avoid or Use Alternate Drug.

• hydrocodone

  Serious - Use Alternative (1)buprenorphine subdermal implant 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. .

• hydroxychloroquine sulfate

  Serious - Use Alternative (1)buprenorphine subdermal implant and hydroxychloroquine sulfate both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyzine

  Monitor Closely (1)buprenorphine subdermal implant 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

• ibutilide

  Serious - Use Alternative (1)buprenorphine subdermal implant and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

• idelalisib

  Monitor Closely (1)idelalisib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• iloperidone

  Monitor Closely (1)iloperidone will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

• imatinib

  Monitor Closely (1)imatinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• imipramine

  Monitor Closely (1)imipramine, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and imipramine both increase QTc interval. Avoid or Use Alternate Drug.

• indinavir

  Monitor Closely (1)indinavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• inotuzumab

  Serious - Use Alternative (1)buprenorphine subdermal implant and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.

• isocarboxazid

  Monitor Closely (1)isocarboxazid, buprenorphine subdermal implant. 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.

• isoflurane

  Serious - Use Alternative (1)buprenorphine subdermal implant and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.

• isoniazid

  Monitor Closely (1)isoniazid will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of buprenorphine subdermal implant 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

  Monitor Closely (1)itraconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  Serious - Use Alternative (2)ivosidenib will decrease the level or effect of buprenorphine subdermal implant 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 subdermal implant and ivosidenib both decrease QTc interval. Avoid or Use Alternate Drug.

• ketoconazole

  Monitor Closely (1)ketoconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• lapatinib

  Monitor Closely (1)lapatinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.

• lasmiditan

  Monitor Closely (1)lasmiditan, buprenorphine subdermal implant. 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.

• lefamulin

  Contraindicated (1)lefamulin will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.Serious - Use Alternative (1)buprenorphine subdermal implant and lefamulin both increase QTc interval. Avoid or Use Alternate Drug.

• lemborexant

  Monitor Closely (1)lemborexant, buprenorphine subdermal implant. 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

  Monitor Closely (1)lenacapavir will increase the level or effect of buprenorphine subdermal implant 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.

• lenvatinib

  Serious - Use Alternative (1)buprenorphine subdermal implant and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.

• leuprolide

  Serious - Use Alternative (1)buprenorphine subdermal implant and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.

• levofloxacin

  Serious - Use Alternative (1)buprenorphine subdermal implant and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• levoketoconazole

  Monitor Closely (1)levoketoconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• levomilnacipran

  Monitor Closely (1)levomilnacipran, buprenorphine subdermal implant. 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.

• linezolid

  Monitor Closely (1)linezolid, buprenorphine subdermal implant. 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.

• lisdexamfetamine

  Monitor Closely (1)lisdexamfetamine, buprenorphine subdermal implant. 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.

• lithium

  Serious - Use Alternative (1)buprenorphine subdermal implant and lithium both increase QTc interval. Avoid or Use Alternate Drug.

• lofexidine

  Serious - Use Alternative (1)buprenorphine subdermal implant and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

• lonafarnib

  Serious - Use Alternative (1)lonafarnib will increase the level or effect of buprenorphine subdermal implant 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

  Serious - Use Alternative (1)buprenorphine subdermal implant and loperamide both increase QTc interval. Avoid or Use Alternate Drug.

• lopinavir

  Monitor Closely (1)lopinavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

• lorazepam

  Monitor Closely (1)lorazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• lumacaftor/ivacaftor

  Monitor Closely (1)lumacaftor/ivacaftor will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• macimorelin

  Serious - Use Alternative (1)buprenorphine subdermal implant and macimorelin both increase QTc interval. Avoid or Use Alternate Drug.

• maprotiline

  Monitor Closely (2)maprotiline, buprenorphine subdermal implant. 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 subdermal implant and maprotiline both increase QTc interval. Use Caution/Monitor.

• mefloquine

  Serious - Use Alternative (1)buprenorphine subdermal implant and mefloquine both increase QTc interval. Avoid or Use Alternate Drug.

• methadone

  Serious - Use Alternative (1)buprenorphine subdermal implant and methadone both increase QTc interval. Avoid or Use Alternate Drug.

• methamphetamine

  Monitor Closely (1)methamphetamine, buprenorphine subdermal implant. 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.

• methylene blue

  Monitor Closely (1)methylene blue, buprenorphine subdermal implant. 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.

• metoclopramide intranasal

  Serious - Use Alternative (1)buprenorphine subdermal implant, 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.

• metronidazole

  Monitor Closely (1)metronidazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• midazolam

  Monitor Closely (1)midazolam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, buprenorphine subdermal implant. 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.

• midostaurin

  Serious - Use Alternative (1)buprenorphine subdermal implant and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

• mifepristone

  Serious - Use Alternative (1)buprenorphine subdermal implant and mifepristone both increase QTc interval. Avoid or Use Alternate Drug.

• milnacipran

  Monitor Closely (1)milnacipran, buprenorphine subdermal implant. 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

  Monitor Closely (1)mirtazapine, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and mirtazapine both increase QTc interval. Avoid or Use Alternate Drug.

• mitotane

  Monitor Closely (1)mitotane will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• mobocertinib

  Serious - Use Alternative (1)buprenorphine subdermal implant and mobocertinib both increase QTc interval. Avoid or Use Alternate Drug.

• moxifloxacin

  Serious - Use Alternative (1)buprenorphine subdermal implant and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• nafcillin

  Monitor Closely (1)nafcillin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• nefazodone

  Monitor Closely (2)nefazodone, buprenorphine subdermal implant. 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.
  
  nefazodone will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• nelfinavir

  Monitor Closely (1)nelfinavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• netupitant/palonosetron

  Monitor Closely (1)netupitant/palonosetron will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• nevirapine

  Monitor Closely (1)nevirapine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• nicardipine

  Monitor Closely (1)nicardipine will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• nilotinib

  Serious - Use Alternative (1)buprenorphine subdermal implant and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• nortriptyline

  Monitor Closely (1)nortriptyline, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide

  Serious - Use Alternative (1)buprenorphine subdermal implant and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  Serious - Use Alternative (1)buprenorphine subdermal implant and ofloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• olanzapine

  Serious - Use Alternative (1)buprenorphine subdermal implant 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

  Serious - Use Alternative (1)buprenorphine subdermal implant, oliceridine. Other (see comment). Avoid or Use Alternate Drug. Comment: Concomitant use may reduce analgesic effect of oliceridine and/or precipitate withdrawal symptoms.

• olopatadine intranasal

  Serious - Use Alternative (1)buprenorphine subdermal implant 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

  Serious - Use Alternative (1)buprenorphine subdermal implant and ondansetron both increase QTc interval. Avoid or Use Alternate Drug.

• osilodrostat

  Serious - Use Alternative (1)buprenorphine subdermal implant and osilodrostat both increase QTc interval. Avoid or Use Alternate Drug. Dose dependent QT prolongation - avoid drugs known to prolong the QT interval

• osimertinib

  Serious - Use Alternative (1)buprenorphine subdermal implant and osimertinib both increase QTc interval. Avoid or Use Alternate Drug.

• oxaliplatin

  Serious - Use Alternative (1)buprenorphine subdermal implant and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

• oxazepam

  Monitor Closely (1)oxazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• ozanimod

  Serious - Use Alternative (2)ozanimod and buprenorphine subdermal implant 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 subdermal implant and ozanimod both increase QTc interval. Avoid or Use Alternate Drug.

• paliperidone

  Serious - Use Alternative (1)buprenorphine subdermal implant and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

• panobinostat

  Serious - Use Alternative (1)buprenorphine subdermal implant and panobinostat both increase QTc interval. Avoid or Use Alternate Drug.

• paroxetine

  Monitor Closely (1)paroxetine, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.

• pasireotide

  Serious - Use Alternative (1)buprenorphine subdermal implant and pasireotide both increase QTc interval. Avoid or Use Alternate Drug.

• pazopanib

  Serious - Use Alternative (1)buprenorphine subdermal implant and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

• pentamidine

  Serious - Use Alternative (1)buprenorphine subdermal implant and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

• pentobarbital

  Monitor Closely (1)pentobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• perphenazine

  Monitor Closely (1)buprenorphine subdermal implant and perphenazine both increase QTc interval. Use Caution/Monitor.

• phendimetrazine

  Monitor Closely (1)phendimetrazine, buprenorphine subdermal implant. 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

  Monitor Closely (1)phenelzine, buprenorphine subdermal implant. 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.

• phenobarbital

  Monitor Closely (1)phenobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• phenytoin

  Monitor Closely (1)phenytoin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• pimavanserin

  Serious - Use Alternative (1)buprenorphine subdermal implant and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

• pimozide

  Serious - Use Alternative (1)buprenorphine subdermal implant and pimozide both increase QTc interval. Contraindicated.

• pitolisant

  Serious - Use Alternative (1)buprenorphine subdermal implant and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

• ponesimod

  Serious - Use Alternative (1)buprenorphine subdermal implant and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

• posaconazole

  Contraindicated (1)buprenorphine subdermal implant and posaconazole both increase QTc interval. Contraindicated.Monitor Closely (1)posaconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• pregabalin

  Monitor Closely (1)pregabalin, buprenorphine subdermal implant. 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.

• primaquine

  Serious - Use Alternative (1)buprenorphine subdermal implant and primaquine both increase QTc interval. Avoid or Use Alternate Drug.

• primidone

  Monitor Closely (1)primidone will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• procainamide

  Serious - Use Alternative (1)buprenorphine subdermal implant and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

• prochlorperazine

  Monitor Closely (1)buprenorphine subdermal implant and prochlorperazine both decrease QTc interval. Use Caution/Monitor.

• promethazine

  Serious - Use Alternative (1)buprenorphine subdermal implant and promethazine both decrease QTc interval. Avoid or Use Alternate Drug.

• propafenone

  Serious - Use Alternative (1)buprenorphine subdermal implant and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

• protriptyline

  Monitor Closely (1)protriptyline, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• quazepam

  Monitor Closely (1)quazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• quetiapine

  Serious - Use Alternative (1)buprenorphine subdermal implant and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.

• quinidine

  Serious - Use Alternative (1)buprenorphine subdermal implant and quinidine both increase QTc interval. Avoid or Use Alternate Drug.

• quinine

  Serious - Use Alternative (1)buprenorphine subdermal implant and quinine both increase QTc interval. Avoid or Use Alternate Drug.

• quinupristin/dalfopristin

  Monitor Closely (1)quinupristin/dalfopristin will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• ranolazine

  Monitor Closely (1)buprenorphine subdermal implant and ranolazine both increase QTc interval. Use Caution/Monitor.

• rasagiline

  Monitor Closely (1)rasagiline, buprenorphine subdermal implant. 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.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

• rifabutin

  Monitor Closely (1)rifabutin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• rifapentine

  Minor (1)rifapentine will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• rilpivirine

  Serious - Use Alternative (1)buprenorphine subdermal implant and rilpivirine both increase QTc interval. Avoid or Use Alternate Drug.

• risperidone

  Serious - Use Alternative (1)buprenorphine subdermal implant and risperidone both increase QTc interval. Avoid or Use Alternate Drug.

• ritonavir

  Monitor Closely (1)ritonavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• romidepsin

  Serious - Use Alternative (1)buprenorphine subdermal implant and romidepsin both increase QTc interval. Avoid or Use Alternate Drug.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• safinamide

  Monitor Closely (1)safinamide, buprenorphine subdermal implant. 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.

• saquinavir

  Monitor Closely (1)saquinavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and saquinavir both increase QTc interval. Avoid or Use Alternate Drug.

• schisandra

  Monitor Closely (1)schisandra will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• secobarbital

  Monitor Closely (1)secobarbital will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• selegiline

  Monitor Closely (1)selegiline, buprenorphine subdermal implant. 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.

• selegiline transdermal

  Monitor Closely (1)selegiline transdermal, buprenorphine subdermal implant. 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.

• selinexor

  Serious - Use Alternative (1)selinexor, buprenorphine subdermal implant. 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

  Serious - Use Alternative (1)buprenorphine subdermal implant and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

• serdexmethylphenidate/dexmethylphenidate

  Monitor Closely (1)serdexmethylphenidate/dexmethylphenidate, buprenorphine subdermal implant. 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

  Monitor Closely (2)sertraline, buprenorphine subdermal implant. 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 will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and sertraline both increase QTc interval. Avoid or Use Alternate Drug.

• sevoflurane

  Serious - Use Alternative (1)buprenorphine subdermal implant and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

• siponimod

  Serious - Use Alternative (1)buprenorphine subdermal implant and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

• solifenacin

  Serious - Use Alternative (1)buprenorphine subdermal implant and solifenacin both increase QTc interval. Avoid or Use Alternate Drug.

• sorafenib

  Serious - Use Alternative (1)buprenorphine subdermal implant and sorafenib both increase QTc interval. Avoid or Use Alternate Drug.

• sotalol

  Serious - Use Alternative (1)buprenorphine subdermal implant and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

• St John's Wort

  Monitor Closely (1)St John's Wort will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• sufentanil SL

  Serious - Use Alternative (1)buprenorphine subdermal implant 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

  Serious - Use Alternative (1)buprenorphine subdermal implant and sunitinib both increase QTc interval. Avoid or Use Alternate Drug.

• suvorexant

  Monitor Closely (1)suvorexant and buprenorphine subdermal implant both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant may be necessary

• tacrolimus

  Serious - Use Alternative (1)buprenorphine subdermal implant and tacrolimus both increase QTc interval. Avoid or Use Alternate Drug.

• tazemetostat

  Monitor Closely (1)tazemetostat will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• telavancin

  Serious - Use Alternative (1)buprenorphine subdermal implant and telavancin both increase QTc interval. Avoid or Use Alternate Drug.

• telotristat ethyl

  Monitor Closely (1)telotristat ethyl will decrease the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inducer for signs and symptoms of withdrawal. If the dose of the concomitant CYP3A4 inducer cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inducer is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for overmedication.

• temazepam

  Monitor Closely (1)temazepam increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

• tetrabenazine

  Serious - Use Alternative (1)buprenorphine subdermal implant and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

• tetracycline

  Monitor Closely (1)tetracycline will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• thioridazine

  Contraindicated (1)buprenorphine subdermal implant and thioridazine both increase QTc interval. Contraindicated.

• tipranavir

  Monitor Closely (1)tipranavir will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• toremifene

  Serious - Use Alternative (1)buprenorphine subdermal implant and toremifene both increase QTc interval. Avoid or Use Alternate Drug.

• tranylcypromine

  Monitor Closely (1)tranylcypromine, buprenorphine subdermal implant. 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.

• trazodone

  Monitor Closely (1)trazodone, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

• triclabendazole

  Serious - Use Alternative (1)buprenorphine subdermal implant and triclabendazole both increase QTc interval. Avoid or Use Alternate Drug.

• trifluoperazine

  Monitor Closely (1)buprenorphine subdermal implant and trifluoperazine both decrease QTc interval. Use Caution/Monitor.

• trimipramine

  Monitor Closely (1)trimipramine, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.

• triptorelin

  Serious - Use Alternative (1)buprenorphine subdermal implant and triptorelin both increase QTc interval. Avoid or Use Alternate Drug.

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• valerian

  Serious - Use Alternative (1)valerian and buprenorphine subdermal implant both increase sedation. Avoid or Use Alternate Drug.

• vandetanib

  Serious - Use Alternative (1)buprenorphine subdermal implant and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.

• vardenafil

  Serious - Use Alternative (1)buprenorphine subdermal implant and vardenafil both increase QTc interval. Avoid or Use Alternate Drug.

• vemurafenib

  Serious - Use Alternative (1)buprenorphine subdermal implant and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.

• venlafaxine

  Monitor Closely (1)venlafaxine, buprenorphine subdermal implant. 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.Serious - Use Alternative (1)buprenorphine subdermal implant and venlafaxine both decrease QTc interval. Avoid or Use Alternate Drug.

• verapamil

  Monitor Closely (1)verapamil will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

• voclosporin

  Serious - Use Alternative (1)buprenorphine subdermal implant and voclosporin both increase QTc interval. Avoid or Use Alternate Drug.

• voriconazole

  Monitor Closely (1)voriconazole will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.Serious - Use Alternative (1)buprenorphine subdermal implant and voriconazole both increase QTc interval. Avoid or Use Alternate Drug.

• vorinostat

  Serious - Use Alternative (1)buprenorphine subdermal implant and vorinostat both increase QTc interval. Avoid or Use Alternate Drug.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of buprenorphine subdermal implant 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

  Serious - Use Alternative (1)buprenorphine subdermal implant and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.