What the FDA labels say about taking them together
Methadone and pregabalin
Methadone's FDA label of December 8, 2025 names pregabalin in its drug interactions section; pregabalin's label does not name methadone itself but warns about its class (Opioids (opioid agonists)). The methadone label: “Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death.”
Check it at the source: the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC); the pregabalin FDA label on DailyMed (effective April 15, 2025, Viatris Specialty LLC).
What does the methadone label say about pregabalin?
Methadone label, drug interactionsBenzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. … anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol.
Methadone label, warnings and precautionsRisks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Methadone hydrochloride tablets with benzodiazepines and/or other CNS depressants (e.g., alcohol, non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids).
Diskets label (Hikma Pharmaceuticals USA Inc., December 1, 2025), drug interactionsBenzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death. … anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol.
Diskets label (Hikma Pharmaceuticals USA Inc., December 1, 2025), warnings and precautionsRisks from Concomitant Use of Benzodiazepines or Other CNS Depressants with Methadone Concomitant use of methadone and benzodiazepines and/or other CNS depressants (e.g., alcohol, non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), increases the risk of adverse reactions, including overdose and death.
Source: FDA drug label (Diskets, NDA017058), Hikma Pharmaceuticals USA Inc., effective December 1, 2025 (SPL set e6af84de-cbfc-4a3b-bd73-6bcf77337168), via openFDA
Source: FDA drug label (Methadone Hydrochloride), Epic Pharma, LLC, effective December 8, 2025 (SPL set 6da7501b-b881-4bc7-891a-74214a00a3ac), via openFDA; the full label on DailyMed
What does the pregabalin label say about methadone?
Pregabalin's label does not name methadone itself; it warns about its class (Opioids (opioid agonists)):
Pregabalin label, warnings and precautionsThere is evidence from case reports, human studies, and animal studies associating LYRICA with serious, life-threatening, or fatal respiratory depression when co-administered with central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment.
Pregabalin label, warnings and precautionsWhen the decision is made to co-prescribe LYRICA with another CNS depressant, particularly an opioid, or to prescribe LYRICA to patients with underlying respiratory impairment, monitor patients for symptoms of respiratory depression and sedation, and consider initiating LYRICA at a low dose.
Source: FDA drug label (Lyrica), NDA021446 (Upjohn), as published by Viatris Specialty LLC, effective April 15, 2025 (SPL set d4734e7d-5079-455e-8ff5-8f4539c998a9), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Methadone | Pregabalin | |
|---|---|---|
| Labeled for | Pain, Opioid use disorder | Nerve pain and fibromyalgia, Seizures and epilepsy |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.177 per tablet 10 mg tablet | $0.0571 per capsule 100 mg capsule |
| Shortage now | No current entry | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once