What the FDA labels say about taking them together
Fentanyl and midazolam
Midazolam's FDA label of January 1, 2024 names fentanyl in its boxed warning section; fentanyl's label does not name midazolam itself but warns about its class (Benzodiazepines). The midazolam label: “The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. …”
Check it at the source: the fentanyl FDA label on DailyMed (effective March 6, 2026, Hikma Pharmaceuticals USA Inc.); the midazolam FDA label on DailyMed (effective January 1, 2024, Fresenius Kabi USA, LLC).
What does the fentanyl label say about midazolam?
Fentanyl's label does not name midazolam itself; it warns about its class (Benzodiazepines):
Fentanyl label, boxed warningTo reduce the risk of respiratory depression, proper dosing and titration of Fentanyl Citrate Injection are essential. ( 5.2 ) Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Fentanyl label, boxed warningRisks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Source: FDA drug label (Fentanyl Citrate), Hikma Pharmaceuticals USA Inc., effective March 6, 2026 (SPL set ce5db1c2-feb1-4ad2-847a-d02e865bd47e), via openFDA; the full label on DailyMed
What does the midazolam label say about fentanyl?
Midazolam label, boxed warningSevere hypotension and seizures have been reported following rapid IV administration, particularly with concomitant use of fentanyl (see DOSAGE AND ADMINISTRATION for complete information).
Midazolam label, drug interactionsIn neonates, however, severe hypotension has been reported with concomitant administration of fentanyl.
N/A label (Rafa Laboratories, Ltd., February 18, 2026), drug interactionsOther CNS Depressants and Alcohol The sedative effect of Midazolam Injection is accentuated by concomitantly administered medication that depresses the central nervous system, particularly opioids (e.g., morphine, meperidine, and fentanyl), secobarbital, and droperidol, and also by alcohol [see Warnings and Precautions (5.1, 5.4, 5.6)].
Nayzilam label (UCB, Inc., January 19, 2023), drug interactions7.2 Opioids Clinical Impact: The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABA A sites and opioids interact primarily at mu receptors. … Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required [see ]. Examples: Morphine, hydrocodone, oxymorphone, codeine, fentanyl
Midazolam In Sodium Chloride label (WG Critical Care, LLC., July 31, 2025), warnings and precautionsMidazolam administered rapidly as an intravenous injection (i.e., less than 2 minutes) has been associated with severe hypotension in neonates, particularly when the patient has also received fentanyl.
Source: FDA drug label (N/A, NDA216359), Rafa Laboratories, Ltd., effective February 18, 2026 (SPL set d7362b4d-68a3-99a0-e053-2995a90a4f60), via openFDA
Source: FDA drug label (Nayzilam, NDA211321), UCB, Inc., effective January 19, 2023 (SPL set 2b29422e-54d5-4a49-8522-e9cf752368c3), via openFDA
Source: FDA drug label (Midazolam), Fresenius Kabi USA, LLC, effective January 1, 2024 (SPL set 1cc9ba6e-fa1b-405e-9de8-720c567b2a73), 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
| Fentanyl | Midazolam | |
|---|---|---|
| Labeled for | Pain | n/a |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $1.79 per mL 100 mcg/2 mL vial | $0.233 per mL 2 mg/2 mL vial |
| Shortage now | In shortage | In shortage |
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