Buprenorphine and Aripiprazole Lauroxil: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Aripiprazole Lauroxil
Buprenorphine
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
You've been prescribed two medicines that can affect your body in overlapping ways. Aripiprazole lauroxil (Aristada) is a long-acting antipsychotic, and buprenorphine is used for pain or opioid use disorder. Both can slightly affect the heart's rhythm (something called QT prolongation), and both can calm the nervous system. Together they may cause more drowsiness, slowed breathing, or, in serious cases, worse heart-rhythm changes.
This doesn't mean you can't take both. Your care team can manage it by watching you more closely, using the lowest effective doses, and sometimes checking your heart with an EKG. Please keep taking both as prescribed and talk with your pharmacist or doctor about any unusual sleepiness or breathing trouble.
Effect: Additive QT prolongation plus additive CNS and respiratory depression. Neither agent's effect is mediated by prodrug activation here; the concern is pharmacodynamic overlap, not a PK conversion issue.
- Mechanism: Both agents can prolong the QT interval; buprenorphine and aripiprazole both contribute to sedation and respiratory depression.
- Direction: Increased risk of arrhythmia, sedation, respiratory depression, and overdose death.
- Evidence: Probable; severity major; onset unspecified.
- Management: Use lowest effective doses, monitor sedation/respiratory status, consider baseline and follow-up ECG and electrolytes, and strongly consider prescribing naloxone. Do not withhold MAT.
What happens
An increased risk of QT interval prolongation and an increased risk of CNS and respiratory depression
Interaction Deep Dive
Do not combine buprenorphine with agents capable of prolonging the QT interval. When these drugs are given together, the likelihood of respiratory depression, deep sedation, coma, and death rises. Discontinuing benzodiazepines or other CNS depressants is favored over using them alongside buprenorphine. Depending on the situation, it may be suitable to observe the patient at a higher level of care or to implement a taper. In other situations, slowly weaning a patient off a prescribed benzodiazepine or other CNS depressant, or reducing to the lowest dose that remains effective, may be appropriate. Should concurrent use be unavoidable, exercise caution in monitoring and management; think about alternative treatments for anxiety or insomnia, and give strong consideration to prescribing naloxone so that opioid overdose can be treated on an emergency basis2. A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) who also took benzodiazepines or other CNS depressants (for instance, medications used for insomnia) faced a heightened risk of death. Based on an analysis of pooled nationwide death certificate data spanning 2010 to 2014, most overdose deaths involving buprenorphine and methadone also involved concurrent CNS depressant use. Whether the risk of overdose death associated with concurrent CNS depressant drugs varied between buprenorphine and methadone remains unknown 3.
Why it happens (mechanism)
Additive QT interval prolongation; additive CNS depression
How to manage this interaction
This combination is flagged as major, but it can be managed, and you should not stop either medicine on your own.
- Keep taking both as prescribed unless your prescriber tells you otherwise.
- Your care team may monitor you more closely, use the lowest effective dose, and may check your heart rhythm with an EKG.
- They may consider prescribing naloxone for emergency use.
- Tell your pharmacist or doctor right away about severe drowsiness, confusion, slowed or shallow breathing, fainting, or a racing/irregular heartbeat.
- Mention every other sedating medicine, alcohol, or sleep/anxiety drug you use.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) A Swedish epidemiological study found that patients on methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, drugs used to treat insomnia) have a higher risk of death. Among MAT-prescribed patients (aged 18 to 50), the study examined the risk of fatal overdose, non-overdose related mortality, and all-cause mortality during periods when CNS depressants were prescribed compared with periods without CNS depressant therapy, between July 1, 2005 and December 31, 2012. The findings showed an increased risk of all-cause mortality (adjusted hazard ratio (HR) 1.44; 95% CI, 0.93 to 2.23) and non-overdose related mortality (HR 1.74; 95% CI 1.00 to 3.01) with MAT plus benzodiazepine treatment; however, these data were not deemed statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods of coadministration of MAT and non-benzodiazepines, only the fatal overdose and all-cause mortality data reached statistical significance; HR 2.34 (95% CI, 1.37 to 3.99) and HR 1.33 (95% CI, 1.12 to 2.45), respectively. The authors did not compare the benzodiazepine cohort with the non-benzodiazepine cohort because they did not adjust for the indication of use of the drugs 3.
b) In a study of pooled nationwide death certificate data spanning 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were often cited as contributors to those deaths. Concurrent ALPRAZolam use was noted in 18.1% of cases, followed by oxyCODONE (10.1%), cocaine (9.6%), heroin (9%), and diazePAM (6.6%). The FDA reported 322 drug overdose deaths in 2014 that involved buprenorphine. Of these 322 deaths, 32.9% involved ALPRAZolam, 17.4% involved clonazePAM, 11.2% involved diazePAM, 11.2% involved heroin, and 9.9% involved fentanyl. The absolute number of deaths involving methadone was 10 times that of deaths involving buprenorphine, though confounding factors and differences in drug utilization were not taken into account. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is not known 3.
c) Thorough QT studies of buprenorphine products have shown modest QT prolongation of 15 msec or less 1.
Common questions
Can I take Buprenorphine and Aripiprazole Lauroxil together?
Taking aripiprazole lauroxil with buprenorphine raises the risk of heart-rhythm changes and dangerous sedation or slowed breathing, so keep taking both as prescribed but ask your care team about closer monitoring and having naloxone on hand. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Aripiprazole Lauroxil interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Buprenorphine and Aripiprazole Lauroxil interaction managed?
This combination is flagged as major, but it can be managed, and you should not stop either medicine on your own. Keep taking both as prescribed unless your prescriber tells you otherwise. Your care team may monitor you more closely, use the lowest effective dose, and may check your heart rhythm with an EKG. They may consider prescribing naloxone for emergency use. Tell your pharmacist or doctor r… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Buprenorphine or Aripiprazole Lauroxil need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: SUBUTEX(R) sublingual tablets, buprenorphine sublingual tablets. Indivior Inc (per FDA), North Chesterfield, VA, 2021. DailyMed
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA urges caution about withholding opioid addiction medications from patients taking benzodiazepines or CNS depressants: careful medication management can reduce risks. US Food and Drug Administration (FDA). Silver Spring, MD. 2017.
Keep reading about Aripiprazole Lauroxil
Keep reading about Buprenorphine
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