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What the FDA labels say about taking them together

Methadone and nalbuphine

Methadone's FDA label of December 8, 2025 names nalbuphine in its drug interactions section; nalbuphine'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 methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC); the nalbuphine FDA label on DailyMed (effective December 31, 2025, Hospira, Inc.).

What does the methadone label say about nalbuphine?

Methadone label, drug interactions

Clinical 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 interactions

Mixed 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 precautions

Avoid 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

What does the nalbuphine label say about methadone?

Nalbuphine's label does not name methadone itself; it warns about its class (Opioids (opioid agonists)):

Nalbuphine label, warnings

Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.

Nalbuphine label, boxed warning

SERIOUS AND LIFE-THREATENING RISKS FROM USE OF NALBUPHINE HYDROCHLORIDE INJECTION ‎ Addiction, Abuse, and Misuse Because the use of Nalbuphine Hydrochloride 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 (Nalbuphine Hydrochloride), Hospira, Inc., effective December 31, 2025 (SPL set 6025e8d4-5083-4c3a-58a0-050e7b0b6150), 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

18Methadone generic labelers
6Nalbuphine generic labelers
MethadoneNalbuphine
Labeled forPain, Opioid use disorderPain
Boxed warningYesYes
Pharmacy cost (NADAC)$0.177 per tablet 10 mg tablet$4.32 per mL 10 mg/mL ampul
Shortage nowNo current entryNo 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?