Buprenorphine and Paregoric: 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
Buprenorphine
Paregoric
No brand names on record
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.
Both of these are opioids. Buprenorphine is used for pain or opioid dependence, and paregoric is an older opioid liquid (it contains morphine) that's mainly used for diarrhea. Taking them together can add up, and that can make you very sleepy, slow your breathing, and in serious cases lead to dangerously deep sedation.
There's also a smaller chance of something called serotonin syndrome, which can cause agitation, shakiness, sweating, and a fast heartbeat. The good news is this is very manageable. Your care team can adjust your doses, keep a closer eye on you, or choose a safer option. Please don't stop either medicine on your own. Just check in with your pharmacist or doctor.
Effect: Additive CNS and respiratory depression plus an increased risk of serotonin syndrome when buprenorphine is combined with paregoric (opium tincture; contains morphine and has serotonergic potential).
- Mechanism: Additive CNS/respiratory depression from two opioid agents; additive serotonergic activity. Neither is a prodrug relevant to this PD interaction.
- Severity/Evidence: Major; probable. Onset unspecified.
- Risks: Profound sedation, respiratory depression, coma, death.
- Management: Avoidance preferred. If coadministration is necessary, use the lowest effective doses, monitor for sedation, respiratory depression, and serotonin syndrome (clonus, hyperreflexia, autonomic instability), especially at initiation and dose changes. Discontinue buprenorphine if serotonin syndrome is suspected.
What happens
An increased risk of serotonin syndrome and an increased risk of respiratory and CNS depression
Interaction Deep Dive
Using buprenorphine together with a serotonergic CNS depressant can produce additive CNS depression, along with a heightened risk of serotonin syndrome, respiratory depression, deep sedation, coma, and death. Rather than concurrent use, discontinuing the other CNS depressant is the preferred approach. Depending on the situation, it may be suitable to monitor the patient in a higher level of care or to implement a taper. Alternatively, slowly weaning a patient off a prescribed benzodiazepine or another CNS depressant, or reducing to the lowest effective dose, may be appropriate. When concurrent use cannot be avoided, watch for sedation, respiratory depression, and the signs and symptoms of serotonin syndrome. Observe the patient closely, especially when starting therapy and when adjusting the dose of the serotonergic agent. If serotonin syndrome is suspected, stop buprenorphine and consider alternative treatments for anxiety or insomnia21.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS and respiratory depression
How to manage this interaction
Both drugs are opioids, so combining them adds their sedating and breathing-slowing effects. Because of this, avoiding the combination is generally preferred.
- Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Do not stop or change doses on your own.
- Your care team may lower one dose to the lowest effective amount, taper one drug, or monitor you more closely, especially when starting or adjusting a medication.
- Ask whether a safer alternative exists for the reason paregoric was prescribed.
- Get urgent help for very slow or shallow breathing, extreme drowsiness, or agitation, shaking, sweating, and a racing heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) A Swedish epidemiological study reported that patients receiving methadone- or buprenorphine-based medication-assisted treatment (MAT) together with benzodiazepines or other CNS depressants (for example, drugs used to treat insomnia) have an increased risk of death. Between July 1, 2005 and December 31, 2012, the risk of fatal overdose, non-overdose related mortality, and all-cause mortality was analyzed by comparing periods when CNS depressants were prescribed to periods without CNS depressant therapy in MAT prescribed patients (aged 18 to 50). 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 combined MAT and benzodiazepine treatment; however, these data were not considered statistically significant. Although the results indicated an increased risk of fatal overdose, non-overdose mortality, and all-cause mortality during periods when MAT and non-benzodiazepines were coadministered, only the data for fatal overdose and all-cause mortality 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 for which the drugs were used 3.
b) According to a study using aggregate nationwide death certificate data from 2010 to 2014, 3495 drug overdose deaths were reported in 2014. Methadone and other CNS depressants were frequently reported as contributors to those deaths. Concurrent alprazolam use was reported 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 involving 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 methadone-involved deaths was 10 times the number of buprenorphine-involved deaths, although confounding factors and differences in drug utilization were not accounted for. Whether the risk of overdose death with concomitant CNS depressant drugs differed between buprenorphine and methadone is unknown 3.
Common questions
Can I take Buprenorphine and Paregoric together?
Combining buprenorphine and paregoric adds two opioids together, raising the risk of dangerous sedation, slowed breathing, and (less often) serotonin syndrome. Keep taking both as prescribed and talk with your pharmacist or doctor, who can adjust doses, monitor you, or choose a safer option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Paregoric 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 Paregoric interaction managed?
Both drugs are opioids, so combining them adds their sedating and breathing-slowing effects. Because of this, avoiding the combination is generally preferred. Keep taking both exactly as prescribed unless your prescriber tells you otherwise. Do not stop or change doses on your own. Your care team may lower one dose to the lowest effective amount, taper one drug, or monitor you more closely, especi… 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 Paregoric 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 Buprenorphine
Keep reading about Paregoric
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