Diazepam Nasal Spray and Oxymorphone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Oxymorphone
No brand names on recordDiazepam Nasal Spray
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased risk of respiratory and CNS depression
Interaction Deep Dive
Reserve the concomitant use of oxyMORphone and CNS depressants to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. Consider using a lower dose of oxyMORphone or the CNS depressant and closely monitor for sedation and respiratory depression23. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 3.
Why it happens (mechanism)
Additive CNS depression
Literature reports
3 reports — tap to read
a) In a study, the rate of nonmedical use-related emergency department visits occurring between 2004 and 2011 and involving opioid analgesics and benzodiazepines significantly increased from 11 to 34.2 per 100,000. Drug overdose deaths due to prescribed and greater than prescribed doses of both drug classes also significantly increased from 0.6 to 1.7 per 100,000, and overdoses deaths due to benzodiazepines significantly increased from 18% to 31% 1.
b) In a prospective cohort study, the rate of overdose deaths involving the dispensing of both opioid analgesics and benzodiazepines was 10 times higher compared with dispensing of opioid analgesics alone (7 vs 0.7 per 10,000 person years) 1.
c) In a cohort study of data from 2004 to 2009, the risk of fatal overdose significantly increased by 2.33 fold in patients taking opioid analgesics with a history of a benzodiazepine prescription and increased by 3.86 fold in those with a current benzodiazepine prescription compared with those taking opioid analgesics without a history of a benzodiazepine prescription. The risk of drug overdose deaths increased with increasing daily doses of benzodiazepines 1.
Common questions
Can I take Diazepam Nasal Spray and Oxymorphone together?
Increased risk of respiratory and CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diazepam Nasal Spray and Oxymorphone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Diazepam Nasal Spray or Oxymorphone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (3)
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. US Food and Drug Administration (FDA). Silver Spring, MD. 2016.
- Product Information: OPANA(R) oral tablets, oxymorphone HCl oral tablets. Endo Pharmaceuticals Inc (per FDA), Malvern, PA, 2019. DailyMed
- Product Information: OPANA(R) ER oral extended-release tablets, oxymorphone HCl oral extended-release tablets. Endo Pharmaceuticals Inc (per FDA), Malvern, PA, 2023. DailyMed
Keep reading about Oxymorphone
Keep reading about Diazepam Nasal Spray
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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