What the FDA labels say about taking them together
Buprenorphine and methadone
Buprenorphine's FDA label (Brixadi) of December 31, 2025 names methadone in its warnings and precautions section, and methadone's label names buprenorphine too. The methadone label: “May reduce the analgesic effect of methadone hydrochloride tablets and/or precipitate withdrawal symptoms.”
Check it at the source: the buprenorphine FDA label on DailyMed (effective June 5, 2026); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).
What does the buprenorphine label say about methadone?
Brixadi label (Braeburn Inc., December 31, 2025), warnings and precautionsSigns and Symptoms Because of the partial agonist properties of buprenorphine, BRIXADI injection may precipitate opioid withdrawal signs and symptoms in individuals physically dependent on full opioid agonists such as heroin, morphine, or methadone before the effects of the full opioid agonist have subsided.
Sublocade label (Indivior Inc., July 27, 2026), warnings and precautionsWithdrawal in Patients Dependent on Full Agonist Opioids Because of the partial opioid agonist properties of buprenorphine, buprenorphine may precipitate opioid withdrawal signs and symptoms in persons who are currently physically dependent on full opioid agonists if administered before the effects of the full opioid agonist have subsided, at least 6 hours for short-acting opioids (e.g., heroin, morphine) and 24 hours for long-acting opioids (e.g., methadone).
Source: FDA drug label (Brixadi, NDA210136), Braeburn Inc., effective December 31, 2025 (SPL set 5d8a8fd0-8619-422a-a664-d1d2e8970f48), via openFDA
Source: FDA drug label (Sublocade, NDA209819), Indivior Inc., effective July 27, 2026 (SPL set 6189fb21-9432-45f8-8481-0bfaf3ccde95), via openFDA
Source: FDA drug label (Buprenorphine HCl), SpecGx LLC, effective June 5, 2026 (SPL set b60d514d-a88a-4fa2-a5b0-30ac29e04973), via openFDA; the full label on DailyMed
What does the methadone label say about buprenorphine?
Methadone label, drug interactionsClinical Impact: May reduce the analgesic effect of methadone hydrochloride tablets and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants
Diskets label (Hikma Pharmaceuticals USA Inc., December 1, 2025), drug interactionsMixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: Patients maintained on methadone may experience withdrawal symptoms when given opioid antagonists, mixed agonist/antagonists, and partial agonists. Intervention: Avoid concomitant use. Examples: Butorphanol, nalbuphine, pentazocine, buprenorphine.
Diskets label (Hikma Pharmaceuticals USA Inc., December 1, 2025), warnings and precautionsAvoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist, including DISKETS Dispersible Tablets.
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 (Methadose, NDA017116), SpecGx LLC, effective April 27, 2026 (SPL set 808a9d0b-720b-4034-a862-5122ff514608), 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
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
| Buprenorphine | Methadone | |
|---|---|---|
| Labeled for | Opioid use disorder, Pain | Pain, Opioid use disorder |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.277 per tablet 2 mg tablet sl | $0.177 per tablet 10 mg tablet |
| 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