Tramadol and Diazepam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tramadol
Diazepam 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 CNS depression
Interaction Deep Dive
Concomitant use of traMADol with benzodiazepines increases the risk of respiratory depression, profound sedation, coma, and death. Reserve concomitant use 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 traMADol or the CNS depressant and titrate the dose based on clinical response. Closely monitor the patients for signs and symptoms of sedation and respiratory depression. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose2.
Why it happens (mechanism)
Additive CNS depression
Literature reports
3 reports — tap to read
a) Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics 34.
b) Between 2004 and 2011, there was an increase in nonmedical use-related emergency department visits involving opioid analgesics and benzodiazepines (from 11 to 34.2 per 100,000 population). During this timeframe, drug over dose deaths from taking the prescribed or greater than prescribed doses of both opioid analgesics and benzodiazepines also increased (from 0.6 to 1.7 per 100,000). The proportion of prescription opioid analgesic overdose deaths that were associated with benzodiazepine use also increased from 18% to 31% 1.
c) The rate of overdose death among patients co-dispensed benzodiazepines and opioid analgesics were 10 times higher than patients dispensed opioid analgesics alone (7 per 10,000 person years vs 0.7 per 10,000 person years). Patients taking opioid analgesics who had a history of benzodiazepine prescriptions had an increased risk of fatal overdose compared with patients taking opioid analgesics with no history of benzodiazepine prescription. A similar risk of fatal overdose was observed in patients with a current benzodiazepine prescription. The risk of drug overdose death increased as the daily benzodiazepine dose also increased 1.
Common questions
Can I take Tramadol and Diazepam Nasal Spray together?
Increased risk of CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tramadol and Diazepam Nasal Spray 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 "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Tramadol or Diazepam Nasal Spray 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 (4)
- 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: CONZIP(R) oral extended-release capsules, tramadol HCl oral extended-release capsules. Vertical Pharmaceuticals LLC (per FDA), Alpharetta, GA, 2023. DailyMed
- Product Information: QDOLO oral solution, tramadol HCl oral solution. Athena Bioscience LLC (per FDA), Athena, GA, 2023. DailyMed
- Product Information: Tramadol hydrochloride oral tablets, tramadol hydrochloride oral tablets. Strides Pharma, Inc (per DailyMed), East Brunswick, NJ, 2025. DailyMed
Keep reading about Tramadol
Keep reading about Diazepam Nasal Spray
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