What the FDA labels say about taking them together
Butorphanol and methadone
Methadone's FDA label of December 8, 2025 names butorphanol in its drug interactions section; butorphanol's label does not name methadone itself but warns about its class (Opioids (opioid agonists)). The methadone label: “May reduce the analgesic effect of methadone hydrochloride tablets and/or precipitate withdrawal symptoms.”
Check it at the source: the butorphanol FDA label on DailyMed (effective January 2, 2026, Hospira, Inc.); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).
What does the butorphanol label say about methadone?
Butorphanol's label does not name methadone itself; it warns about its class (Opioids (opioid agonists)):
Butorphanol label, warningsLife-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.
Butorphanol label, boxed warningSERIOUS AND LIFE-THREATENING RISKS FROM USE OF BUTORPHANOL TARTRATE INJECTION Addiction, Abuse, and Misuse Because the use of Butorphanol Tartrate Injection exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see WARNINGS ].
Source: FDA drug label (Butorphanol Tartrate), Hospira, Inc., effective January 2, 2026 (SPL set 9822ca3f-aee2-46e5-8a96-495400e65d10), via openFDA; the full label on DailyMed
What does the methadone label say about butorphanol?
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
| Butorphanol | Methadone | |
|---|---|---|
| Labeled for | Pain | Pain, Opioid use disorder |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $15.46 per mL 10 mg/mL spray | $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