Buprenorphine and Butalbital: 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
Butalbital
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 medicines can slow down your body. Buprenorphine is an opioid used for pain or opioid treatment, and butalbital is a barbiturate often found in headache medicines. Each one on its own can make you sleepy and slow your breathing. When you take them together, those effects can stack on top of each other.
The concern is that your breathing could get too slow or shallow, or that you may feel very drowsy or confused. Please don't stop either medicine on your own. Talk with your pharmacist or doctor, who can make sure you're on the lowest dose you need and keep a close eye on how you're doing.
Interaction: Additive CNS and respiratory depression when buprenorphine (opioid partial agonist) is combined with butalbital (a barbiturate).
- Mechanism: Pharmacodynamic, additive CNS depression. Neither agent is a prodrug; the effect is direct, not metabolic.
- Direction: Enhanced sedation, respiratory depression, hypotension.
- Evidence: Theoretical, but severity rated major given the known risk of opioid plus barbiturate combinations.
- Management: Reserve concurrent use for patients without adequate alternatives. Use the lowest effective doses for the shortest duration. Monitor for sedation and respiratory depression, and counsel on symptoms.
What happens
An increased risk of CNS depression
Interaction Deep Dive
Do not use butalbital together with CNS depressants, because such combined use can intensify the action of the CNS depressants and thereby raise the likelihood of CNS depression1. Prescribing these agents together should be limited to patients in whom other treatment options are insufficient. Keep doses and treatment durations as low as possible and monitor carefully for indications of respiratory depression, sedation included2.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this safely if both drugs are truly needed.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop or change either one on your own.
- Your team will usually reserve this combination for when other options aren't enough, and will use the lowest dose for the shortest time needed.
- They may monitor you more closely for excess drowsiness and breathing problems.
- Get help right away if you notice very slow or shallow breathing, extreme sleepiness, confusion, or trouble waking up.
- Ask your pharmacist before adding anything else sedating, such as alcohol, sleep aids, or muscle relaxers.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Buprenorphine and Butalbital together?
Buprenorphine and butalbital both depress the nervous system, so combining them can add up to dangerous sedation or slowed breathing. Take both only as prescribed and ask your care team to keep doses low and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Butalbital 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 Butalbital interaction managed?
Your care team can manage this safely if both drugs are truly needed. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop or change either one on your own. Your team will usually reserve this combination for when other options aren't enough, and will use the lowest dose for the shortest time needed. They may monitor you more closely for excess drowsines… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Buprenorphine or Butalbital 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 (2)
- Product Information: Butalbital acetaminophen oral tablets, butalbital acetaminophen oral tablets. Burel Pharmaceuticals LLC (per DailyMed), Mason, OH, 2022. DailyMed
- Product Information: Butalbital, Acetaminophen, Caffeine, Codeine Phosphate oral capsules, butalbital, acetaminophen, caffeine, codeine phosphate oral capsules. Actavis Pharma Inc (per FDA), Parsippany, NJ, 2023. DailyMed
Keep reading about Buprenorphine
Keep reading about Butalbital
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