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Suboxone, Suboxone Film Interactions: What to Avoid

Documented interactions for Suboxone, Suboxone Film (Buprenorphine HCl and naloxone HCl (sublingual film)). Each entry cites the prescribing information or FDA safety communication it is based on.

2 contraindicated10 major1 moderate

Interaction summary

SeverityInteracts withClassConcern
ContraindicatedCobicistat or ritonavir (HIV protease inhibitors)Potent CYP3A inhibitorBuprenorphine/naloxone with ritonavir or cobicistat is contraindicated
ContraindicatedMAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue)Monoamine oxidase inhibitorOpioid with MAO inhibitors is contraindicated
MajorAlcohol (ethanol)CNS depressantBuprenorphine with alcohol: additive CNS depression
MajorAlcohol (ethanol)CNS depressantOpioid with alcohol: additive respiratory depression
MajorAntiparasitics (ivermectin, albendazole, praziquantel)AntiparasiticBuprenorphine with agents that increase metabolism: potential for precipitated withdrawal
MajorOther benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam)BenzodiazepineBuprenorphine with benzodiazepine: risk of sedation, respiratory depression, and death
MajorOther benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam)BenzodiazepineOpioid with benzodiazepine: risk of profound sedation, respiratory depression, coma, and death
MajorOther CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants)CNS depressantBuprenorphine with other CNS depressants
MajorOther CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants)CNS depressantOpioid with other CNS depressants: additive respiratory depression
MajorOther gabapentinoids (gabapentin, pregabalin)GabapentinoidOpioid with gabapentinoid: serious breathing difficulties
MajorStrong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St John's Wort)CYP3A4 inducerStrong CYP3A4 inducers reduce buprenorphine exposure
MajorStrong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice)CYP3A4 inhibitorStrong CYP3A4 inhibitors can precipitate withdrawal or raise buprenorphine levels
ModerateOther gabapentinoids (gabapentin, pregabalin)GabapentinoidBuprenorphine with gabapentinoids: additive CNS depression

Detailed interactions

Contraindicated

Buprenorphine/naloxone with ritonavir or cobicistat is contraindicated

With: Cobicistat or ritonavir (HIV protease inhibitors) Potent CYP3A inhibitor

Why it happens

These agents strongly inhibit CYP3A4, which metabolizes buprenorphine. Buprenorphine exposure rises sharply while the opioid antagonist effect falls.

What can happen

The combination can precipitate withdrawal and, at high buprenorphine levels, interfere with naloxone's intended effect.

What to do

Labeling lists the combination as contraindicated. Do not combine without specialist direction.

Basis: Buprenorphine and naloxone sublingual film prescribing information, Contraindications. source

Contraindicated

Opioid with MAO inhibitors is contraindicated

With: MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) Monoamine oxidase inhibitor

Why it happens

MAO inhibitors potentiate opioid effects and impair metabolism.

What can happen

Severe unpredictable reactions including respiratory depression and death.

What to do

Do not combine.

Basis: Opioid-containing product labeling, Contraindications. source

Major

Buprenorphine with alcohol: additive CNS depression

With: Alcohol (ethanol) CNS depressant

Why it happens

Combined central nervous system depression.

What can happen

Sedation, respiratory depression, and overdose are possible.

What to do

Avoid alcohol during buprenorphine therapy.

Basis: Buprenorphine and naloxone sublingual film prescribing information, Warnings. source

Major

Opioid with alcohol: additive respiratory depression

With: Alcohol (ethanol) CNS depressant

Why it happens

Both agents depress the central nervous system and breathing.

What can happen

Respiratory depression, deep sedation, coma, and death.

What to do

Avoid alcohol during opioid therapy.

Basis: Opioid-containing product labeling, Warnings and Precautions. source

Major

Buprenorphine with agents that increase metabolism: potential for precipitated withdrawal

With: Antiparasitics (ivermectin, albendazole, praziquantel) Antiparasitic

Why it happens

Some agents increase CYP3A4 activity or otherwise shift opioid receptor activity, altering the buprenorphine-to-naloxone balance.

What can happen

Withdrawal symptoms in people who are stable on buprenorphine.

What to do

Labeling recommends caution when starting or stopping agents that affect buprenorphine metabolism.

Basis: Buprenorphine and naloxone sublingual film prescribing information, Warnings. source

Major

Buprenorphine with benzodiazepine: risk of sedation, respiratory depression, and death

With: Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) Benzodiazepine

Why it happens

Additive CNS and respiratory depression. Buprenorphine has a ceiling effect on respiratory depression but does not eliminate the risk.

What can happen

Labeling describes combinations with benzodiazepines and other CNS depressants as posing a risk of overdose and death, and notes that the combination is common among people who are already dependent.

What to do

Do not withhold buprenorphine because of benzodiazepine use, but coordinate with the prescriber, monitor closely, and avoid alcohol and other sedatives.

Basis: Buprenorphine and naloxone sublingual film prescribing information, Warnings and Precautions. source

Major

Opioid with benzodiazepine: risk of profound sedation, respiratory depression, coma, and death

With: Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) Benzodiazepine

Why it happens

Additive depression of the central nervous system and respiratory drive.

What can happen

FDA requires a boxed warning on opioid-containing products describing this combination.

What to do

Avoid where possible. If used, lowest effective doses for the shortest duration with monitoring.

Basis: FDA Drug Safety Communication (2016); opioid boxed warning. source

Major

Buprenorphine with other CNS depressants

With: Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) CNS depressant

Why it happens

Additive central nervous system and respiratory depression.

What can happen

Overdose and death are possible, particularly with alcohol and benzodiazepines.

What to do

Avoid alcohol and unapproved sedatives; monitor closely.

Basis: Buprenorphine and naloxone sublingual film prescribing information, Warnings. source

Major

Opioid with other CNS depressants: additive respiratory depression

With: Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) CNS depressant

Why it happens

Additive central nervous system depression and slowed breathing.

What can happen

Respiratory depression and overdose, particularly in older adults.

What to do

Disclose all sedating medications to the prescriber and pharmacist.

Basis: Opioid-containing product labeling, Warnings and Precautions. source

Major

Opioid with gabapentinoid: serious breathing difficulties

With: Other gabapentinoids (gabapentin, pregabalin) Gabapentinoid

Why it happens

Additive respiratory depression.

What can happen

FDA warns of serious breathing difficulties and increased risk of death.

What to do

Use the lowest effective gabapentinoid dose and monitor for slowed breathing.

Basis: FDA Drug Safety Communication (2021). source

Major

Strong CYP3A4 inducers reduce buprenorphine exposure

With: Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, St John's Wort) CYP3A4 inducer

Why it happens

Induction increases buprenorphine metabolism, lowering plasma levels.

What can happen

Withdrawal, reduced efficacy, or opioid craving.

What to do

Labeling warns against strong CYP3A4 inducers with buprenorphine/naloxone.

Basis: Buprenorphine and naloxone sublingual film prescribing information, Drug Interactions. source

Major

Strong CYP3A4 inhibitors can precipitate withdrawal or raise buprenorphine levels

With: Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice) CYP3A4 inhibitor

Why it happens

Buprenorphine clearance falls when CYP3A4 is inhibited, raising exposure and disrupting the buprenorphine-to-naloxone balance.

What can happen

Withdrawal symptoms, or at higher levels, reduced naloxone antagonism.

What to do

Monitoring and dose adjustment may be needed. Ritonavir and cobicistat are contraindicated for this reason.

Basis: Buprenorphine and naloxone sublingual film prescribing information, Drug Interactions. source

Moderate

Buprenorphine with gabapentinoids: additive CNS depression

With: Other gabapentinoids (gabapentin, pregabalin) Gabapentinoid

Why it happens

Additive sedation and respiratory depression.

What can happen

Excessive sedation and slowed breathing are possible.

What to do

Coordinate with the prescriber and monitor for sedation.

Basis: Buprenorphine and naloxone sublingual film prescribing information, Warnings. source

Common questions

What should I know about Suboxone, Suboxone Film interactions?

We have documented 13 interaction classes for Suboxone, Suboxone Film in our dataset. Usually avoided, or used only with explicit prescriber oversight and close monitoring. The most serious items on this page are marked contraindicated or major.

Can I take Suboxone, Suboxone Film with alcohol?

Alcohol interacts with most of the medications on this site because it adds to sedation and slows breathing. For the specific documented risk, see the relevant entry above. The general rule from labeling is to avoid alcohol.

Does an empty result mean Suboxone, Suboxone Film is safe with other drugs?

No. An empty result only means our curated dataset has no matching rule. A pharmacist can run a full interaction screen against every medication and supplement you take.

Related

Editorial Review Board

Clinical review by licensed pharmacists (PharmD)

Every page on this site is reviewed against current FDA prescribing information, DailyMed labelling, DEA scheduling regulations and MedlinePlus monographs before publication. Reviewers have no commercial relationship with any manufacturer or pharmacy.

Last substantive review: October 01, 2026

Sources & references

DailyMed — full prescribing information (National Library of Medicine)
MedlinePlus drug information (National Library of Medicine)
PubChem compound record (National Institutes of Health)
21 CFR Part 1308 — Controlled Substances (eCFR)
Drug Enforcement Administration — drug scheduling

Important

This site provides educational information only and does not sell, prescribe or dispense medications. Always consult a licensed healthcare provider. This page is not medical advice.