Dosing & Uses
Dosage Forms & Strengths
buprenorphine/naloxone
film, sublingual: Schedule III
- 2mg/0.5mg (Suboxone, generic)
- 4mg/1mg (Suboxone, generic)
- 8mg/2mg (Suboxone, generic)
- 12mg/3mg (Suboxone, generic)
- 16mg/4mg (Cassipa)
tablet, sublingual (Zubsolv): Schedule III
- 0.7mg/0.18mg
- 1.4mg/0.36mg
- 2.9mg/0.71mg
- 5.7mg/1.4mg
- 8.6mg/2.1mg
- 11.4mg/2.9mg
buccal film (Bunavail): Schedule III
- 2.1mg/0.3mg
- 4.2mg/0.7mg
- 6.3mg/1mg
tablet, sublingual (generic): Schedule III
- 2mg/0.5mg
- 8mg/2mg
Opioid Dependence
Induction (buprenorphine SL)
- Day 1: 4 mg SL initially; may be repeated after 2 hours if withdrawal symptoms are not relieved; not to exceed 8 mg
- Day 2: If no withdrawal symptoms are present, 4 mg SL; if withdrawal symptoms are present, dose is increased by 4 mg; if symptoms are not relieved after >2 hr, 4 mg is administered; not to exceed 16 mg SL
- Switch to buprenorphine/naloxone for unsupervised maintenance
Induction (buprenorphine/naloxone [Suboxone])
- Caution: buprenorphine/naloxone (Suboxone) induction is only for patients dependent on short-acting opioids (eg, heroin) and not for those dependent on long-acting opioids (eg, methadone); buprenorphine monotherapy is recommended for induction for long-acting opioids
- Day 1: 2 mg/0.5 mg or 4 mg/1 mg SL initially; may titrate upwards in 2-4 mg increments at 2 hr intervals, under supervision; not to exceed 8 mg/2 mg
- Day 2: Up to 16 mg/4 mg SL as a single daily dose
Induction (buprenorphine/naloxone [Zubsolv])
- Caution: buprenorphine/naloxone (Zubsolv) induction is only for patients dependent on short-acting opioids (eg, heroin) and not for those dependent on long-acting opioids (eg, methadone); buprenorphine monotherapy is recommended for induction for long-acting opioids
-
Day 1
- An induction dose of up to 5.7 mg/1.4 mg is recommended, given in divided doses; initiate with 1.4 mg/0.36 mg SL; give remainder of Day 1 dose of up to 4.2 mg/1.08 mg should be divided into doses of 1 to 2 tablets of 1.4 mg/0.36 mg at 1.5 to 2 hr intervals
- Some patients (eg, those with recent exposure to buprenorphine) may tolerate up to 3 x 1.4 mg/0.36 mg SL as a single, second dose
-
Day 2
- A single daily dose up to 11.4 mg/2.9 mg SL is recommended
Induction (buprenorphine/naloxone [Bunavail])
- Caution: buprenorphine/naloxone (Bunavail) induction is only for patients dependent on short-acting opioids (eg, heroin) and not for those dependent on long-acting opioids (eg, methadone); buprenorphine monotherapy is recommended for induction for long-acting opioids
-
Day 1
- The first dose should not be administered <6 hr after the patient last used an opioid
- An induction dose of up to 4.2 mg/0.7 mg is recommended; initiate with 2.1 mg/0.3 mg and repeat at ~2-hr, under supervision, to a total dose of 4.2 mg/0.7 mg based on control of acute withdrawal symptoms
-
Day 2
- A single daily dose up to 8.4 mg/1.4 mg buccal is recommended
Maintenance
-
Suboxone
- Target dose: 12-16 mg/4 mg buprenorphine/naloxone SL as a single daily dose
- Range: 16-24 mg buprenorphine component; not to exceed 32 mg/day
- Progressively adjust buprenorphine/naloxone dose in increments or decrements of 2 mg/0.5 mg or 4 mg/1 mg to level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
-
Zubsolv
- Target dose: 11.4/2.9 mg as a single daily dose
- Range: 2.9/0.71 mg to 17.2/4.2 mg
- Progressively adjust buprenorphine/naloxone dose in increments or decrements of 1.4/0.36 mg or 2.9/0.71 mg to level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
-
Bunavail
- Target dose: 8.4/1.4 mg as a single daily dose
- Range: 2.1/0.3 mg to 12.6/2.1 mg
- Progressively adjust dose in increments or decrements of 2.1/0.3 mg to a level that holds patient in treatment and suppresses opioid withdrawal signs and symptoms
- There is no maximum recommended duration of maintenance treatment; for some patients, treatment may continue indefinitely
-
Cassipa
- Used after induction and stabilization of the patient, and after buprenorphine dose titrated to 16 mg using another marketed product
- If dose needs adjustment in order to maintain treatment and suppress opioid withdrawal signs and symptoms, a different product will be needed; Cassipa comes in a single dose and cannot be adjusted (ie, SL film available only as 16 mg buprenorphine/4 mg naloxone)
- There is no maximum recommended duration of maintenance treatment; for some patients, treatment may continue indefinitely
Dosage Modifications
Hepatic impairment
- Mild: No dosage adjustment necessary
- Moderate: May not be appropriate
- Severe: Avoid use
Renal impairment
- No differences in buprenorphine pharmacokinetics observed between 9 dialysis-dependent and 6 normal patients following IV administration of 0.3 mg buprenorphine
- Renal failure: Unknown
Dosing Considerations
Prior to induction, consideration should be given to the type of opioid dependence (ie, long- or short-acting opioid products, the time since last opioid use, and the degree or level of opioid dependence
To avoid precipitating an opioid withdrawal syndrome, the first dose of buprenorphine/naloxone should be administered only when objective and clear signs of moderate withdrawal are evident, and divided doses should be used
It is recommended that an adequate treatment dose, titrated to clinical effectiveness, be achieved as rapidly as possible
Patients dependent on methadone or long-acting opioid products may be more susceptible to precipitated and prolonged withdrawal during induction than those on short-acting opioid products; buprenorphine monotherapy is recommended in patients taking long-acting opioids instead of buprenorphine/naloxone, which may worsen withdrawal symptoms
Patients dependent on heroin or other short-acting opioid products may be induced with buprenorphine/naloxone or with SL buprenorphine monotherapy
Equivalents
- Zubsolv 5.7/1.4 mg SL provides equivalent buprenorphine exposure to Suboxone 8/2 mg SL
- Bunavail 2.1/0.3 mg buccal provides equivalent buprenorphine exposure to Suboxone 4/1 mg SL
- Bunavail 4.2/0.7 mg buccal provides equivalent buprenorphine exposure to Suboxone 8/2 mg SL
- Bunavail 6.3/1 mg buccal provides equivalent buprenorphine exposure to Suboxone 12/3 mg SL
Access to naloxone for opioid overdose
- Assess need for naloxone upon initiating and renewing treatment
-
Consider prescribing naloxone
- Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
- Household members (including children) or other close contacts at risk for accidental ingestion or overdose
-
Consult patients and caregivers on the following:
- Availability of naloxone for emergency treatment of opioid overdose
- Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (5)
- alvimopan
alvimopan, buprenorphine. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.
- dronedarone
buprenorphine and dronedarone both increase QTc interval. Contraindicated.
- fezolinetant
buprenorphine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
- lefamulin
lefamulin will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.
- thioridazine
buprenorphine and thioridazine both increase QTc interval. Contraindicated.
Serious - Use Alternative (132)
- abametapir
abametapir will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use is warranted, carefully monitor, particularly during treatment initiation and dose adjustment. Discontinue oliceridine if serotonin syndrome is suspected.
- acrivastine
acrivastine and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- alfentanil
buprenorphine, alfentanil. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- alfuzosin
alfuzosin and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- amiodarone
buprenorphine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.
- amisulpride
amisulpride and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.
amisulpride and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - amitriptyline
buprenorphine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
- amoxapine
buprenorphine and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.
- anagrelide
anagrelide and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
buprenorphine and anagrelide both increase QTc interval. Avoid or Use Alternate Drug. - apalutamide
apalutamide will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- apomorphine
apomorphine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- aripiprazole
aripiprazole and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- arsenic trioxide
buprenorphine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.
- artemether
artemether and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- artemether/lumefantrine
artemether/lumefantrine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- asenapine
asenapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
buprenorphine and asenapine both increase QTc interval. Avoid or Use Alternate Drug.
asenapine and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - asenapine transdermal
asenapine transdermal and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
asenapine transdermal and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - atomoxetine
atomoxetine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- avapritinib
avapritinib and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- azithromycin
buprenorphine and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.
- bedaquiline
bedaquiline and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- belladonna and opium
buprenorphine, belladonna and opium. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
buprenorphine decreases effects of benzhydrocodone/acetaminophen by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone (benzhydrocodone prodrug of hydrocodone) and/or precipitate withdrawal symptoms in opioid tolerant patients.
benzhydrocodone/acetaminophen and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate - bremelanotide
bremelanotide will decrease the level or effect of buprenorphine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.
- brexpiprazole
brexpiprazole and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- brimonidine
brimonidine and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- brivaracetam
brivaracetam and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- buprenorphine subdermal implant
buprenorphine subdermal implant and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
- butorphanol
buprenorphine, butorphanol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- calcium/magnesium/potassium/sodium oxybates
buprenorphine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- ceritinib
ceritinib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
ceritinib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. - chloramphenicol
chloramphenicol will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloroquine
chloroquine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- chlorpromazine
buprenorphine and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.
- cimetidine
cimetidine increases effects of buprenorphine by decreasing metabolism. Avoid or Use Alternate Drug.
- ciprofloxacin
buprenorphine and ciprofloxacin both increase QTc interval. Avoid or Use Alternate Drug.
- citalopram
citalopram and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
clarithromycin and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug. - clomipramine
buprenorphine and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.
- clonidine
clonidine, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.
- clozapine
clozapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- codeine
buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- conivaptan
conivaptan will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- crizotinib
crizotinib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- dasatinib
dasatinib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- degarelix
degarelix and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- desflurane
desflurane and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- desipramine
buprenorphine and desipramine both increase QTc interval. Avoid or Use Alternate Drug.
- dextromoramide
buprenorphine, dextromoramide. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- diamorphine
buprenorphine, diamorphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- diazepam intranasal
diazepam intranasal, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- difenoxin hcl
buprenorphine, difenoxin hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- diphenoxylate hcl
buprenorphine, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- dipipanone
buprenorphine, dipipanone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- disopyramide
buprenorphine and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.
- dofetilide
buprenorphine and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.
- dolasetron
dolasetron and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- donepezil
donepezil and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- doxepin
doxepin and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- efavirenz
efavirenz and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- eliglustat
buprenorphine and eliglustat both increase QTc interval. Avoid or Use Alternate Drug.
- eluxadoline
buprenorphine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .
- encorafenib
encorafenib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- entrectinib
entrectinib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- eribulin
eribulin and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin base
buprenorphine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
buprenorphine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin lactobionate
buprenorphine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin stearate
buprenorphine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.
- escitalopram
buprenorphine and escitalopram both increase QTc interval. Avoid or Use Alternate Drug.
- fentanyl
fentanyl, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
buprenorphine decreases effects of fentanyl by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms. - fentanyl intranasal
fentanyl intranasal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
buprenorphine decreases effects of fentanyl intranasal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms. - fentanyl transdermal
fentanyl transdermal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
buprenorphine decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms. - fentanyl transmucosal
fentanyl transmucosal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
buprenorphine decreases effects of fentanyl transmucosal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms. - fexinidazole
fexinidazole and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels and/or prolong QT interval.
fexinidazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates. - fingolimod
fingolimod and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- flecainide
buprenorphine and flecainide both increase QTc interval. Avoid or Use Alternate Drug.
- fluconazole
buprenorphine and fluconazole both increase QTc interval. Contraindicated.
- fluoxetine
buprenorphine and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug.
- fluvoxamine
buprenorphine and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug.
- foscarnet
buprenorphine and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.
- fostemsavir
buprenorphine and fostemsavir both increase QTc interval. Avoid or Use Alternate Drug.
- gemifloxacin
gemifloxacin and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- gemtuzumab
buprenorphine and gemtuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- gilteritinib
gilteritinib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- glasdegib
buprenorphine and glasdegib both increase QTc interval. Avoid or Use Alternate Drug.
- goserelin
buprenorphine and goserelin both increase QTc interval. Avoid or Use Alternate Drug.
- granisetron
granisetron and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- haloperidol
buprenorphine and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.
- histrelin
buprenorphine and histrelin both increase QTc interval. Avoid or Use Alternate Drug.
- hydrocodone
buprenorphine decreases effects of hydrocodone by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Mixed opioid agonists/antagonists and partial opioid agonists may reduce the analgesic effect of hydrocodone and/or precipitate withdrawal symptoms in opioid tolerant patients. .
hydrocodone, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. - hydromorphone
buprenorphine, hydromorphone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- hydroxychloroquine sulfate
buprenorphine and hydroxychloroquine sulfate both increase QTc interval. Avoid or Use Alternate Drug.
- ibutilide
buprenorphine and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.
- idelalisib
idelalisib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- iloperidone
buprenorphine and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.
- imipramine
buprenorphine and imipramine both increase QTc interval. Avoid or Use Alternate Drug.
- inotuzumab
buprenorphine and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- isocarboxazid
isocarboxazid increases toxicity of buprenorphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- isoflurane
isoflurane and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- itraconazole
itraconazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
itraconazole and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug. - ivosidenib
ivosidenib will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
buprenorphine and ivosidenib both decrease QTc interval. Avoid or Use Alternate Drug. - ketoconazole
ketoconazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- lapatinib
buprenorphine and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.
- lefamulin
buprenorphine and lefamulin both increase QTc interval. Avoid or Use Alternate Drug.
- lenvatinib
buprenorphine and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.
- leuprolide
buprenorphine and leuprolide both increase QTc interval. Avoid or Use Alternate Drug.
- levofloxacin
buprenorphine and levofloxacin both increase QTc interval. Avoid or Use Alternate Drug.
- levoketoconazole
levoketoconazole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- levorphanol
buprenorphine, levorphanol. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- linezolid
linezolid increases toxicity of buprenorphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.
- lithium
lithium and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- lofexidine
buprenorphine and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.
- lonafarnib
lonafarnib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- loperamide
buprenorphine and loperamide both increase QTc interval. Avoid or Use Alternate Drug.
- lopinavir
buprenorphine and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.
- macimorelin
buprenorphine and macimorelin both increase QTc interval. Avoid or Use Alternate Drug.
- mefloquine
buprenorphine and mefloquine both increase QTc interval. Avoid or Use Alternate Drug.
- meperidine
buprenorphine, meperidine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- methadone
buprenorphine, methadone. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
buprenorphine and methadone both increase QTc interval. Avoid or Use Alternate Drug. - methylene blue
methylene blue and buprenorphine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities
- metoclopramide intranasal
buprenorphine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
- midostaurin
buprenorphine and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- mifepristone
mifepristone will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
buprenorphine and mifepristone both increase QTc interval. Avoid or Use Alternate Drug. - mirtazapine
mirtazapine and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- mobocertinib
buprenorphine and mobocertinib both increase QTc interval. Avoid or Use Alternate Drug.
- morphine
buprenorphine, morphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- moxifloxacin
buprenorphine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.
- nalbuphine
buprenorphine, nalbuphine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.
- naldemedine
naldemedine, naloxone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive opioid receptor anatagonism and increased risk of opioid withdrawal.
- naloxegol
naloxegol, naloxone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration; potential for additive effect of opioid receptor anatagonism and increased risk of opioid withdrawal.
- nefazodone
nefazodone will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
Monitor Closely (217)
- albuterol
buprenorphine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
albuterol and buprenorphine both increase QTc interval. Use Caution/Monitor. - alfentanil
alfentanil and buprenorphine both increase sedation. Use Caution/Monitor.
- alprazolam
alprazolam and buprenorphine both increase sedation. Use Caution/Monitor.
- amitriptyline
buprenorphine and amitriptyline both increase sedation. Use Caution/Monitor.
- amobarbital
amobarbital and buprenorphine both increase sedation. Use Caution/Monitor.
amobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - amoxapine
buprenorphine and amoxapine both increase sedation. Use Caution/Monitor.
- apalutamide
apalutamide will decrease the level or effect of buprenorphine by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.
- apomorphine
buprenorphine and apomorphine both increase sedation. Use Caution/Monitor.
- arformoterol
arformoterol and buprenorphine both increase QTc interval. Use Caution/Monitor.
- aripiprazole
buprenorphine and aripiprazole both increase sedation. Use Caution/Monitor.
- armodafinil
buprenorphine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- atazanavir
atazanavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity.
- azelastine
azelastine and buprenorphine both increase sedation. Use Caution/Monitor.
- baclofen
baclofen and buprenorphine both increase sedation. Use Caution/Monitor.
- belladonna and opium
buprenorphine and belladonna and opium both increase sedation. Use Caution/Monitor.
- belzutifan
belzutifan will decrease the level or effect of buprenorphine 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.
- benperidol
buprenorphine and benperidol both increase sedation. Use Caution/Monitor.
- benzphetamine
buprenorphine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- bosentan
bosentan will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- brexanolone
brexanolone, buprenorphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brompheniramine
brompheniramine and buprenorphine both increase sedation. Use Caution/Monitor.
- buprenorphine, long-acting injection
buprenorphine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
- butabarbital
butabarbital and buprenorphine both increase sedation. Use Caution/Monitor.
- butalbital
butalbital and buprenorphine both increase sedation. Use Caution/Monitor.
- butorphanol
buprenorphine and butorphanol both increase sedation. Use Caution/Monitor.
- carbamazepine
carbamazepine decreases levels of buprenorphine by increasing metabolism. Use Caution/Monitor. Carbamazepine increases metabolism of buprenorphine; monitor for decreased efficacy.
carbamazepine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - carbinoxamine
carbinoxamine and buprenorphine both increase sedation. Use Caution/Monitor.
- carisoprodol
carisoprodol and buprenorphine both increase sedation. Use Caution/Monitor.
- cenobamate
cenobamate will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
cenobamate, buprenorphine. Either increases effects of the other by sedation. Use Caution/Monitor. - chloral hydrate
chloral hydrate and buprenorphine both increase sedation. Use Caution/Monitor.
- chlordiazepoxide
chlordiazepoxide and buprenorphine both increase sedation. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and buprenorphine both increase sedation. Use Caution/Monitor.
- chlorpromazine
buprenorphine and chlorpromazine both increase sedation. Use Caution/Monitor.
- chlorzoxazone
chlorzoxazone and buprenorphine both increase sedation. Use Caution/Monitor.
- cinnarizine
cinnarizine and buprenorphine both increase sedation. Use Caution/Monitor.
- clemastine
clemastine and buprenorphine both increase sedation. Use Caution/Monitor.
- clobazam
buprenorphine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
- clomipramine
buprenorphine and clomipramine both increase sedation. Use Caution/Monitor.
- clonazepam
clonazepam and buprenorphine both increase sedation. Use Caution/Monitor.
- clorazepate
clorazepate and buprenorphine both increase sedation. Use Caution/Monitor.
- clozapine
buprenorphine and clozapine both increase sedation. Use Caution/Monitor.
- cobicistat
cobicistat will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- codeine
buprenorphine and codeine both increase sedation. Use Caution/Monitor.
- crizotinib
crizotinib increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.
- crofelemer
crofelemer increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- cyclizine
cyclizine and buprenorphine both increase sedation. Use Caution/Monitor.
- cyclobenzaprine
cyclobenzaprine and buprenorphine both increase sedation. Use Caution/Monitor.
- cyproheptadine
cyproheptadine and buprenorphine both increase sedation. Use Caution/Monitor.
- dabrafenib
dabrafenib will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dantrolene
dantrolene and buprenorphine both increase sedation. Use Caution/Monitor.
- daridorexant
buprenorphine 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 increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Carefully titrate dose when initiating buprenorphine, buprenorphine/naloxone, or methadone with patients taking darunavir/cobicstat. When initiating cobicistat in patients taking buprenorphine, buprenorphine/naloxone, or methadone, adjust dose for buprenorphine, buprenorphine/naloxone, or methadone and monitor clinical signs and symptoms.
- desflurane
desflurane and buprenorphine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.
- desipramine
buprenorphine and desipramine both increase sedation. Use Caution/Monitor.
- deutetrabenazine
buprenorphine and deutetrabenazine both increase sedation. Use Caution/Monitor.
deutetrabenazine and buprenorphine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation). - dexamethasone
dexamethasone will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dexchlorpheniramine
dexchlorpheniramine and buprenorphine both increase sedation. Use Caution/Monitor.
- dexfenfluramine
buprenorphine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dexmedetomidine
dexmedetomidine and buprenorphine both increase sedation. Use Caution/Monitor.
- dextromoramide
buprenorphine and dextromoramide both increase sedation. Use Caution/Monitor.
- diamorphine
buprenorphine and diamorphine both increase sedation. Use Caution/Monitor.
- diazepam
diazepam and buprenorphine both increase sedation. Use Caution/Monitor.
- difelikefalin
difelikefalin and buprenorphine both increase sedation. Use Caution/Monitor.
- difenoxin hcl
buprenorphine and difenoxin hcl both increase sedation. Use Caution/Monitor.
- dimenhydrinate
dimenhydrinate and buprenorphine both increase sedation. Use Caution/Monitor.
- diphenhydramine
diphenhydramine and buprenorphine both increase sedation. Use Caution/Monitor.
- diphenoxylate hcl
buprenorphine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
- dipipanone
buprenorphine and dipipanone both increase sedation. Use Caution/Monitor.
- dopexamine
buprenorphine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dosulepin
buprenorphine and dosulepin both increase sedation. Use Caution/Monitor.
- doxepin
buprenorphine and doxepin both increase sedation. Use Caution/Monitor.
- doxylamine
doxylamine and buprenorphine both increase sedation. Use Caution/Monitor.
- droperidol
buprenorphine and droperidol both increase sedation. Use Caution/Monitor.
- efavirenz
efavirenz will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- elagolix
elagolix will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
- encorafenib
encorafenib, buprenorphine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- enzalutamide
enzalutamide will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- esketamine intranasal
esketamine intranasal, buprenorphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- estazolam
estazolam and buprenorphine both increase sedation. Use Caution/Monitor.
- ethanol
buprenorphine and ethanol both increase sedation. Use Caution/Monitor.
- etomidate
etomidate and buprenorphine both increase sedation. Use Caution/Monitor.
- etravirine
etravirine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fedratinib
fedratinib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fenfluramine
buprenorphine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- flibanserin
buprenorphine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
- fluphenazine
buprenorphine and fluphenazine both increase sedation. Use Caution/Monitor.
buprenorphine and fluphenazine both increase QTc interval. Use Caution/Monitor. - flurazepam
flurazepam and buprenorphine both increase sedation. Use Caution/Monitor.
- fosamprenavir
fosamprenavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. .
- fosphenytoin
fosphenytoin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- gabapentin
gabapentin, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- gabapentin enacarbil
gabapentin enacarbil, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- ganaxolone
buprenorphine and ganaxolone both increase sedation. Use Caution/Monitor.
- haloperidol
buprenorphine and haloperidol both increase sedation. Use Caution/Monitor.
- hydromorphone
buprenorphine and hydromorphone both increase sedation. Use Caution/Monitor.
- hydroxyzine
hydroxyzine and buprenorphine both increase sedation. Use Caution/Monitor.
hydroxyzine and buprenorphine 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 - iloperidone
buprenorphine and iloperidone both increase sedation. Use Caution/Monitor.
iloperidone increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4. - imipramine
buprenorphine and imipramine both increase sedation. Use Caution/Monitor.
- indinavir
indinavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. .
- istradefylline
istradefylline will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- ketamine
ketamine and buprenorphine both increase sedation. Use Caution/Monitor.
- ketotifen, ophthalmic
buprenorphine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
- lasmiditan
lasmiditan, buprenorphine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
- lemborexant
lemborexant, buprenorphine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
- lenacapavir
lenacapavir will increase the level or effect of buprenorphine 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.
- letermovir
letermovir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- levorphanol
buprenorphine and levorphanol both increase sedation. Use Caution/Monitor.
- lofepramine
buprenorphine and lofepramine both increase sedation. Use Caution/Monitor.
- lofexidine
buprenorphine and lofexidine both increase sedation. Use Caution/Monitor.
- lopinavir
lopinavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity.
- loprazolam
loprazolam and buprenorphine both increase sedation. Use Caution/Monitor.
- lorazepam
lorazepam and buprenorphine both increase sedation. Use Caution/Monitor.
- lorlatinib
lorlatinib will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lormetazepam
lormetazepam and buprenorphine both increase sedation. Use Caution/Monitor.
- loxapine
buprenorphine and loxapine both increase sedation. Use Caution/Monitor.
- loxapine inhaled
buprenorphine and loxapine inhaled both increase sedation. Use Caution/Monitor.
- lumacaftor/ivacaftor
lumacaftor/ivacaftor will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lurasidone
lurasidone, buprenorphine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
- maprotiline
buprenorphine and maprotiline both increase sedation. Use Caution/Monitor.
buprenorphine and maprotiline both increase QTc interval. Use Caution/Monitor. - marijuana
buprenorphine and marijuana both increase sedation. Use Caution/Monitor.
- mavacamten
buprenorphine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.
- melatonin
buprenorphine and melatonin both increase sedation. Use Caution/Monitor.
- meperidine
buprenorphine and meperidine both increase sedation. Use Caution/Monitor.
- meprobamate
buprenorphine and meprobamate both increase sedation. Use Caution/Monitor.
- metaxalone
metaxalone and buprenorphine both increase sedation. Use Caution/Monitor.
- methadone
buprenorphine and methadone both increase sedation. Use Caution/Monitor.
- methocarbamol
methocarbamol and buprenorphine both increase sedation. Use Caution/Monitor.
- methylenedioxymethamphetamine
buprenorphine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- midazolam
midazolam and buprenorphine both increase sedation. Use Caution/Monitor.
- midazolam intranasal
midazolam intranasal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
- mirtazapine
buprenorphine and mirtazapine both increase sedation. Use Caution/Monitor.
- mitotane
mitotane will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- morphine
buprenorphine and morphine both increase sedation. Use Caution/Monitor.
- motherwort
buprenorphine and motherwort both increase sedation. Use Caution/Monitor.
- moxonidine
buprenorphine and moxonidine both increase sedation. Use Caution/Monitor.
- nabilone
buprenorphine and nabilone both increase sedation. Use Caution/Monitor.
- nafcillin
nafcillin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nalbuphine
buprenorphine and nalbuphine both increase sedation. Use Caution/Monitor.
- nelfinavir
nelfinavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. .
- nevirapine
nevirapine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- nortriptyline
buprenorphine and nortriptyline both increase sedation. Use Caution/Monitor.
- olanzapine
buprenorphine and olanzapine both increase sedation. Use Caution/Monitor.
- oliceridine
oliceridine, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
- ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)
ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increases levels of buprenorphine and active metabolite norbuprenorphine; no dose adjustment of buprenorphine is required, but closely monitor for sedation and cognitive effects
- opium tincture
buprenorphine and opium tincture both increase sedation. Use Caution/Monitor.
- orphenadrine
orphenadrine and buprenorphine both increase sedation. Use Caution/Monitor.
- osilodrostat
osilodrostat and buprenorphine both increase QTc interval. Use Caution/Monitor.
- oxazepam
oxazepam and buprenorphine both increase sedation. Use Caution/Monitor.
- oxcarbazepine
oxcarbazepine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- oxycodone
buprenorphine and oxycodone both increase sedation. Use Caution/Monitor.
- oxymorphone
buprenorphine and oxymorphone both increase sedation. Use Caution/Monitor.
- paliperidone
buprenorphine and paliperidone both increase sedation. Use Caution/Monitor.
- papaveretum
buprenorphine and papaveretum both increase sedation. Use Caution/Monitor.
- papaverine
buprenorphine and papaverine both increase sedation. Use Caution/Monitor.
- paroxetine
buprenorphine and paroxetine both increase QTc interval. Use Caution/Monitor.
- pegvisomant
buprenorphine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.
- pentazocine
buprenorphine and pentazocine both increase sedation. Use Caution/Monitor.
- pentobarbital
pentobarbital and buprenorphine both increase sedation. Use Caution/Monitor.
pentobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - perampanel
perampanel and buprenorphine both increase sedation. Use Caution/Monitor.
- perphenazine
buprenorphine and perphenazine both increase sedation. Use Caution/Monitor.
buprenorphine and perphenazine both increase QTc interval. Use Caution/Monitor. - phenobarbital
phenobarbital and buprenorphine both increase sedation. Use Caution/Monitor.
phenobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - phenylephrine PO
buprenorphine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
- phenytoin
phenytoin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- pholcodine
buprenorphine and pholcodine both increase sedation. Use Caution/Monitor.
- pimozide
buprenorphine and pimozide both increase sedation. Use Caution/Monitor.
- pregabalin
pregabalin, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.
- primidone
primidone and buprenorphine both increase sedation. Use Caution/Monitor.
primidone will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. - prochlorperazine
buprenorphine and prochlorperazine both increase sedation. Use Caution/Monitor.
buprenorphine and prochlorperazine both decrease QTc interval. Use Caution/Monitor. - promethazine
promethazine and buprenorphine both increase sedation. Use Caution/Monitor.
- propofol
propofol and buprenorphine both increase sedation. Use Caution/Monitor.
- propylhexedrine
buprenorphine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- protriptyline
buprenorphine and protriptyline both increase sedation. Use Caution/Monitor.
- quazepam
quazepam and buprenorphine both increase sedation. Use Caution/Monitor.
- quetiapine
buprenorphine and quetiapine both increase sedation. Use Caution/Monitor.
- ramelteon
buprenorphine and ramelteon both increase sedation. Use Caution/Monitor.
- ranolazine
buprenorphine and ranolazine both increase QTc interval. Use Caution/Monitor.
- remimazolam
remimazolam, buprenorphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
- ribociclib
ribociclib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifabutin
rifabutin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifapentine
rifapentine will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- risperidone
buprenorphine and risperidone both increase sedation. Use Caution/Monitor.
- ritonavir
ritonavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity.
- rolapitant
rolapitant will increase the level or effect of buprenorphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.
- rucaparib
rucaparib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- saquinavir
saquinavir increases levels of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. .
- scullcap
buprenorphine and scullcap both increase sedation. Use Caution/Monitor.
- secobarbital
secobarbital and buprenorphine both increase sedation. Use Caution/Monitor.
secobarbital will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May also enhance CNS depressant effect of buprenorphine - sevoflurane
sevoflurane and buprenorphine both increase sedation. Use Caution/Monitor.
- shepherd's purse
buprenorphine and shepherd's purse both increase sedation. Use Caution/Monitor.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of buprenorphine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.
- sodium sulfate/potassium sulfate/magnesium sulfate
sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of buprenorphine by QTc interval. Use Caution/Monitor. Consider predose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.
- St John's Wort
St John's Wort will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- stiripentol
stiripentol, buprenorphine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
stiripentol, buprenorphine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence. - sufentanil
buprenorphine and sufentanil both increase sedation. Use Caution/Monitor.
- suvorexant
suvorexant and buprenorphine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary
- tapentadol
buprenorphine and tapentadol both increase sedation. Use Caution/Monitor.
- tazemetostat
tazemetostat will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- temazepam
temazepam and buprenorphine both increase sedation. Use Caution/Monitor.
- thioridazine
buprenorphine and thioridazine both increase sedation. Use Caution/Monitor.
- thiothixene
buprenorphine and thiothixene both increase sedation. Use Caution/Monitor.
- tipranavir
tipranavir will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- topiramate
buprenorphine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
- tramadol
buprenorphine and tramadol both increase sedation. Use Caution/Monitor.
- trazodone
buprenorphine and trazodone both increase sedation. Use Caution/Monitor.
- triazolam
triazolam and buprenorphine both increase sedation. Use Caution/Monitor.
- triclofos
triclofos and buprenorphine both increase sedation. Use Caution/Monitor.
- trifluoperazine
buprenorphine and trifluoperazine both increase sedation. Use Caution/Monitor.
buprenorphine and trifluoperazine both decrease QTc interval. Use Caution/Monitor. - trimipramine
buprenorphine and trimipramine both increase sedation. Use Caution/Monitor.
- triprolidine
triprolidine and buprenorphine both increase sedation. Use Caution/Monitor.
- valbenazine
valbenazine and buprenorphine both increase QTc interval. Use Caution/Monitor.
- xylometazoline
buprenorphine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ziconotide
buprenorphine and ziconotide both increase sedation. Use Caution/Monitor.
- ziprasidone
buprenorphine and ziprasidone both increase sedation. Use Caution/Monitor.
- zotepine
buprenorphine and zotepine both increase sedation. Use Caution/Monitor.
Minor (11)
- acetazolamide
acetazolamide will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- brimonidine
brimonidine increases effects of buprenorphine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- cyclophosphamide
cyclophosphamide will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dextroamphetamine
dextroamphetamine increases effects of buprenorphine by unspecified interaction mechanism. Minor/Significance Unknown.
- elvitegravir
elvitegravir increases levels of buprenorphine by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects.
elvitegravir decreases levels of naloxone by unknown mechanism. Minor/Significance Unknown. No dose adjustment of buprenorphine/naloxone is required upon coadministration with VITEKTA. Patients should be closely monitored for sedation and cognitive effects. - eucalyptus
buprenorphine and eucalyptus both increase sedation. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of buprenorphine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lidocaine
lidocaine increases toxicity of buprenorphine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.
- sage
buprenorphine and sage both increase sedation. Minor/Significance Unknown.
- ziconotide
ziconotide, buprenorphine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.
Adverse Effects
>10%
Headache (28-36.4%)
Withdrawal syndrome (24-25.2%)
Insomnia (14-23%)
Pain (22.4%)
Nausea (7-15%)
Hyperhidrosis (14%)
Asthenia (6.5-14%)
Constipation (5-12.1%)
Abdominal pain (11.2%)
1-10%
Diarrhea (10%)
Vasodilation or peripheral edema (9.3%)
Chills (6-7.5%)
Vomiting (4-7.5%)
Postmarketing Reports
Adrenal insufficiency
Anaphylaxis
Serotonin syndrome
Hepatotoxicity
Glossodynia
Glossitis
Oral mucosal erythema
Oral hypoesthesia Stomatitis
Warnings
Contraindications
Hypersensitivity
Cautions
Significant respiratory depression may occur with therapeutic doses
Use with caution in hypothyroidism, preexisting respiratory compromise, obstructive pulmonary disease, cor pulmonale, decreased respiratory reserve and kyphoscoliosis, myxedema, adrenocortical insufficiency, alcohol intoxication, alcohol withdrawal syndrome, coma, severe renal impairment, geriatric or debilitated patients, delirium tremens, toxic psychoses, kyphoscoliosis, prostatic hypertrophy, urethral stricture, comatose patients, central nervous system (CNS) depression, biliary tract dysfunction, severe hepatic impairment, head injury, intracranial lesions, and intracranial hypertension or conditions in which intracranial pressure (ICP) may be increased
Use caution with concurrent use of other CNS depressants
Respiratory sedation is dose-dependent; usual doses may depress respiration to same degree as 10 mg of parenteral morphine
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper
Use caution in patients with history of ileus or bowel obstruction
May cause orthostatic hypotension; use caution in patients with hypovolemia, cardiovascular disease, or drugs that may worsen hypertension
Effects in CNS depression may impair ability to perform tasks that require mental alertness
Life-threatening neonatal syndrome may occur in newborns following maternal exposure to opioids; treat according to protocols developed by neonatology experts; prescribers should discuss with patients importance and benefits of management of opioid addiction throughout pregnancy
Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; unknown whether effects on fertility are reversible
Use caution when switching between formulations; certain sublingual film strengths may have greater bioavailability compared to the same strength of sublingual tablet; monitor for overdosing or underdosing when switching formulations
Buprenorphine may precipitate acute narcotic withdrawal in opioid-dependent patients upon rapid discontinuation or rapid taper; taper dose gradually when discontinuing therapy
Because it contains naloxone, drug is highly likely to produce marked and intense withdrawal signs and symptoms if misused parenterally by individual dependent on full opioid agonists such as heroin, morphine, or methadone
May obscure diagnosis or clinical course of patients with acute abdominal conditions
Cases of adrenal insufficiency reported with opioid use, more often following greater than one month of use; symptoms may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure; if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids; wean patient off of opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers; other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency
Advise pregnant women receiving opioid addiction treatment with sublingual film of risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Due to risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose
Drug can be abused in a manner similar to other opioids; consider this when prescribing or dispensing buprenorphine in situations when clinician is concerned about increased risk of misuse, abuse, or diversion
QTc prolongation
- Thorough QT studies with buprenorphine products have demonstrated QT prolongation less than or equal to 15 msec; this QTc prolongation effect does not appear to be mediated by hERG channels; based on these two findings, buprenorphine is unlikely to be pro-arrhythmic when used alone in patients without risk factors; the risk of combining buprenorphine with other QT-prolonging agents is not known
- Consider these observations in clinical decisions when prescribing this medication to patients with risk factors such as hypokalemia, bradycardia, recent conversion from atrial fibrillation, congestive heart failure, digitalis therapy, baseline QT prolongation, subclinical long-QT syndrome, or severe hypomagnesemia
Increased risk of dental problems
- On January 12, 2022, FDA warned of potential dental problems associated with transmucosal buprenorphine-containing products (eg, buccal, sublingual)
- Cases of dental caries, some severe (eg, tooth fracture, tooth loss), reported following use of transmucosal buprenorphine-containing products; reported events include cavities, tooth decay, dental abscesses/infection, rampant caries, tooth erosion, fillings falling out, and, in some cases, total tooth loss
- Treatment for these events included tooth extraction, root canal, dental surgery, as well as other restorative procedures (eg, fillings, crowns, implants, dentures); multiple cases were reported in individuals without any prior history of dental problems
- Despite these risks, buprenorphine is an important treatment option for opioid use disorder and pain, and the benefits of these medicines clearly outweigh the risks
- Review patient’s health before initiating with transmucosal buprenorphine
- Refer patients to dental care services and encourage them to have regular dental checkups while receiving therapy; educate patients to seek dental care and strategies to maintain or improve oral health while being treated with transmucosal buprenorphine-containing products
- Strategies include, but are not limited to, gently rinsing teeth and gums with water and then swallowing after completely dissolved in oral mucosa; advise patients to wait for at least one hour after taking drug before brushing teeth
- Counsel patients regarding potential for dental problems and importance of taking extra steps after the medicine has completely dissolved, including gently rinsing teeth and gums with water and then swallow; advise to wait at least 1 hour before brushing their teeth
- Dentists treating patients taking transmucosal buprenorphine should perform a baseline dental evaluation and caries risk assessment, establish a dental caries preventive plan, and encourage regular dental checkups
Coadministration with benzodiazepines
- Life-threating respiratory depression and death may occur; many, but not all, postmarketing reports regarding coma and death involved misuses by self-injection or were associated with concomitant use of benzodiazepines or other CNS depressants, including alcohol; warn patients of potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment
- Concomitant use of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose and death; medication-assisted treatment of opioid use disorder, however, should not be categorically denied to patients taking these drugs; prohibiting or creating barriers to treatment can pose an even greater risk of morbidity and mortality due to the opioid use disorder alone
- If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response; follow patients closely for signs and symptoms of respiratory depression and sedation
- Develop strategies to manage use of prescribed or illicit benzodiazepines or other CNS depressants at initiation of buprenorphine treatment, or if it emerges as a concern during treatment; adjustments to induction procedures and additional monitoring may be required; there is no evidence to support dose limitations or arbitrary caps of buprenorphine as a strategy to address benzodiazepine use in buprenorphine-treated patients; however, if a patient is sedated at the time of buprenorphine dosing, delay or omit the buprenorphine dose if appropriate
- Cessation of benzodiazepines or other CNS depressants is preferred in most cases of concomitant use. In some cases, monitoring in a higher level of care for taper may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate
- Ensure that other healthcare providers prescribing benzodiazepines or other CNS depressants are aware of the patient’s buprenorphine treatment and coordinate care to minimize the risks associated with concomitant use
- If concomitant use with benzodiazepine is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose
- Confirm patients are taking their medications as prescribed and are not diverting or supplementing with illicit drugs; toxicology screening should test for prescribed and illicit benzodiazepines
Patient access to naloxone for emergency treatment of opioid overdose
- Assess potential need for naloxone; consider prescribing for emergency treatment of opioid overdose
- Consult on availability and ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines
- Educate patients regarding the signs and symptoms of respiratory depression and to call 911 or seek immediate emergency medical help in the event of a known or suspected overdose
Pregnancy & Lactation
Pregnancy
Data on use of buprenorphine, one of the active ingredients are limited; however, these data do not indicate an increased risk of major malformations specifically due to buprenorphine exposure; there are limited data from randomized clinical trials in women maintained on buprenorphine that were not designed appropriately to assess the risk of major malformations; the extremely limited data on sublingual naloxone exposure in pregnancy are not sufficient to evaluate a drug associated risk; dosage adjustments of buprenorphine may be required during pregnancy, even if patient was maintained on stable dose prior to pregnancy; withdrawal signs and symptoms should be monitored closely and dose adjusted as necessary
Neonates whose mothers have been taking opioids long term may exhibit withdrawal signs, either at birth and/or in the nursery, because they have developed physical dependence; neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts
Lactation
Caution should be exercised when therapy is administered to nursing women; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition; advise breastfeeding women taking buprenorphine products to monitor infant for increased drowsiness and breathing difficulties
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Buprenorphine: Semisynthetic narcotic mixed agonist-antagonist analgesic; exerts agonistic effects at mu and delta opioid receptors in CNS, as well as antagonistic effects at kappa opioid receptor
Naloxone: Potent antagonist at mu opioid receptors and produces opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists when administered parenterally
Absorption
Suboxone
- Peak plasma time: Buprenorphine, 1.53-1.72 hr; naloxone, 0.77-0.81 hr
- Peak plasma concentration: Buprenorphine, 0.947-3.37 ng/mL; naloxone, 54.1-193 pg/mL
Zubsolv
- Bioavailability differs from that of Suboxone
- Compared with Suboxone 8/2 mg, Zubsolv 5.7/1.4 mg provides equivalent buprenorphine exposure and 12% lower naloxone exposure
Bunavail
- Bioavailability differs from that of Suboxone
- Compared with Suboxone 8/2 mg, Bunavail 4.2/0.7 mg provides equivalent buprenorphine exposure and 33% lower naloxone exposure
- Coadministration of liquids reduced the systemic exposure up to 59% for buprenorphine and up to 76% for naloxone (depending on the pH of the liquid)
Distribution
Protein bound: Buprenorphine, 96% (primarily alpha and beta globulin); naloxone, 45% (primarily albumin)
Metabolism
Buprenorphine: Metabolized by N-dealkylation via CYP3A4 to norbuprenorphine (active metabolite) and by glucuronidation
Naloxone: Metabolized by direct glucuronidation to naloxone-3-glucuronide, as well as by N-dealkylation and reduction of 6-oxo group
Elimination
Excretion: Buprenorphine, urine (30%) and feces (69%)
Half-life
- Suboxone, Zubsolv: 24-42 hr (buprenorphine); 2-12 hr (naloxone)
- Cassipa: 35-37 hr (buprenorphine); 5.6-6.6 hr (naloxone)
- Bunavail: 16.4-27.5 hr (buprenorphine); 1.9-2.4 hr (naloxone)
Administration
Sublingual Administration
Switching between SL tablet and SL film: Potential for greater bioavailability with SL film than with generic SL tablets (monitor for over- or underdosing)
Instruct patient to rinse mouth with small volume of room-temperature water before placement of the SL film strip or tablet under their tongue
High pH beverages should be avoided prior to dosing
Place film/tablet under the tongue, close to the base on the left or right side; keep in place until completely dissolved
Advise patients not to eat or drink anything until the film is completely dissolved
Use entire tablet/film; do not chew, cut, or swallow SL or buccal preparations
Bunavail Buccal Film Application
Use the tongue to wet the inside of the cheek or rinse mouth with water to moisten the area immediately before placement
Open package immediately prior to use
Hold the buccal film with clean, dry fingers with the text (BN2, BN4, or BN6) facing up, THEN
Place the side of the film with the text (BN2, BN4, or BN6) against the inside of the cheek
Press and hold the film in place for 5 seconds
Buccal film completely dissolves after applicationInstruct the patient to avoid manipulating the film(s) with the tongue or finger(s) and avoid drinking or eating food until the film(s) dissolve
Multiple Bunavail films
- If multiple films are needed, the patient should immediately apply the next film according to the steps above
- When 2 films are required for one dose, the patient should place one film on the inside of one cheek and the other film on the inside of the other cheek
- For doses requiring multiple films, no more than 2 films should be applied to the inside of one cheek at a time
Images
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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