Levorphanol and Hydromorphone Rectal: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Levorphanol
Hydromorphone Rectal
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 and an increased risk of serotonin syndrome
Interaction Deep Dive
Concomitant use of opioids, such as HYDROmorphone, with serotonergic CNS depressant drugs may result in increased risk of serotonergic syndrome, profound sedation, hypotension, respiratory depression, coma death. Reserve the concomitant use of HYDROmorphone 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 HYDROmorphone or the CNS depressant and closely monitor for sedation, respiratory depression, and signs and symptoms of serotonin syndrome. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments for serotonin syndrome. Discontinue HYDROmorphone if serotonin syndrome is suspected312. Consider prescribing naloxone for the emergency treatment of opioid overdose. Inform and educate the patients and caregivers on the signs and symptoms of respiratory depression (including sedation) 1.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
Literature reports
2 reports — tap to read
a) Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs 21.
b) 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 12.
Common questions
Can I take Levorphanol and Hydromorphone Rectal together?
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome Always confirm with your pharmacist or prescriber before making any change.
How serious is the Levorphanol and Hydromorphone Rectal 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 Levorphanol or Hydromorphone Rectal 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)
- Product Information: DILAUDID(R) oral tablets, oral solution, hydromorphone HCl oral tablets, oral solution. Rhodes Pharmaceuticals LP (per FDA), Wilson, NC, 2023. DailyMed
- Product Information: DILAUDID(R) intravenous injection, intramuscular injection, subcutaneous injection, hydromorphone HCl intravenous injection, intramuscular injection, subcutaneous injection. Fresenius Kabi. (per FDA), Lake Zurich, IL, 2023. DailyMed
- Product Information: EXALGO(R) oral extended-release tablets, hydromorphone HCl oral extended-release tablets. SpecGx LLC (per FDA), Webster Groves, MO, 2019. DailyMed
Keep reading about Levorphanol
Keep reading about Hydromorphone Rectal
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist