Buprenorphine and Pregabalin: 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
Pregabalin
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.
Buprenorphine (an opioid pain or addiction medicine) and pregabalin (Lyrica, used for nerve pain or seizures) can both slow down your brain and your breathing. When you take them together, those calming effects can add up. That can make you more sleepy or dizzy, and in rare cases it can slow your breathing to a dangerous level.
This is mostly a theoretical concern based on how these drugs work, but breathing problems are serious, so it's worth taking seriously. The good news is that your care team can manage this well, often by starting pregabalin at a low dose and keeping an eye on how you feel. Please talk with your pharmacist or doctor before changing anything.
Mechanism: additive CNS depression from two agents with sedative and respiratory-depressant properties (mu-opioid partial agonist plus alpha-2-delta ligand). Neither is a prodrug; this is a pharmacodynamic, not pharmacokinetic, interaction.
Effect/direction: increased risk of sedation and respiratory depression, potentially serious, life-threatening, or fatal.
Evidence: theoretical/class-based; severity major. Onset unspecified.
Management:
- Consider initiating pregabalin at a low dose.
- Monitor for sedation and respiratory depression, especially with underlying respiratory impairment.
- If respiratory depression occurs: close observation, supportive measures, and reduce or withdraw CNS depressants including pregabalin.
What happens
An increased risk of respiratory depression
Interaction Deep Dive
Serious respiratory depression that may be life-threatening or fatal has occurred when pregabalin is taken together with other CNS depressants. When pregabalin is given alongside another CNS depressant, particularly an opioid and in patients who already have respiratory impairment, watch for signs of sedation and respiratory depression, and consider starting pregabalin at a low dose. Respiratory depression should be handled through close observation, supportive care, and lowering or discontinuing CNS depressants (pregabalin included)1.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
These two medicines are often prescribed together on purpose, so do not stop either one on your own. The goal is to use them safely.
- Your team may start pregabalin at a low dose and adjust it individually.
- They may monitor you more closely for heavy sleepiness or slowed breathing, especially if you have any breathing or lung problems.
- Avoid adding alcohol or other sedating substances without checking first.
Get emergency help right away for very slow or shallow breathing, extreme drowsiness, confusion, or trouble waking someone. Raise any new grogginess with your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) Data from the FDA Adverse Event Reporting System (FAERS) database indicate that from January 1, 2012 to October 26, 2017, there were 49 reports of respiratory depression associated with gabapentinoids (gabapentin n=15; pregabalin n=34). A respiratory risk factor, such as age-related decline in lung function or concurrent use of a CNS depressant, was noted in 92% of these cases. There were twelve fatalities (24%), and every death reported at least one respiratory risk factor. Small randomized trials in healthy volunteers have shown that gabapentinoids, both by themselves and combined with opioids, reduce respiratory function. End-tidal CO2 rose with an additive effect when pregabalin was combined with remifentanil, and hourly apneic episodes occurred more often during gabapentin exposure than during placebo exposure. Observational studies indicate a higher risk of postoperative respiratory depression when preoperative gabapentinoids are used compared with no preoperative gabapentinoid exposure 2.
b) When a single 600 mg dose of gabapentin enacarbil (another gabapentinoid) was given 2 hours after a single 60 mg dose of morphine sulfate extended-release to 18 subjects, increased somnolence or sedation, dizziness, and nausea were recorded on a visual analog scale compared with the agents given alone. There were no changes in Cmax or AUC of gabapentin, morphine, or morphine's active metabolite 3.
c) In a study involving 12 volunteers, a single oral 60 mg dose of controlled-release morphine was given 2 hours before a single oral 600 mg dose of immediate-release gabapentin (another gabapentinoid). The mean gabapentin AUC in these patients was 44% higher than when gabapentin was administered alone. The pharmacokinetics of morphine were not affected 45.
Common questions
Can I take Buprenorphine and Pregabalin together?
Taking buprenorphine and pregabalin together can add up to cause dangerous drowsiness and slowed breathing, so keep taking both as prescribed but watch for heavy sedation or breathing trouble and report it to your care team right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Pregabalin 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 Pregabalin interaction managed?
These two medicines are often prescribed together on purpose, so do not stop either one on your own. The goal is to use them safely. Your team may start pregabalin at a low dose and adjust it individually. They may monitor you more closely for heavy sleepiness or slowed breathing, especially if you have any breathing or lung problems. Avoid adding alcohol or other sedating substances without check… 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 Pregabalin 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 (5)
- Product Information: Pregabalin oral capsule, pregabalin oral capsule. Alembic Pharmaceuticals, Inc (per Dailymed), Bedminster, NJ, 2025. DailyMed
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) when used with CNS depressants or in patients with lung problems. US Food and Drug Administration (FDA). Silver Spring, MD. 2019.
- Product Information: HORIZANT(R) oral extended-release tablets, gabapentin enacarbil oral extended-release tablets. GlaxoSmithKline (per FDA), Research Triangle Park, NC, 2013. DailyMed
- Product Information: Neurontin(R) oral capsules, tablets, solution, gabapentin oral capsules, tablets, solution. Parke-Davis, New York, NY, 2010. DailyMed
- Product Information: GRALISE(R) oral tablets, gabapentin oral tablets. Abbott Laboratories, North Chicago, IL, 2011. DailyMed
Keep reading about Buprenorphine
Keep reading about Pregabalin
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