Clomipramine and Hydromorphone Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Clomipramine
Hydromorphone Injection
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
An increased risk of serotonin syndrome, an increased risk of CNS depression and an increased risk of paralytic ileus
Interaction Deep Dive
Exert caution with concomitant use of clomiPRAMINE with HYDROmorphone (CNS depressant) due to increased risk of additive CNS effects4. Concomitant use of opioids, such as HYDROmorphone, with serotonergic drugs, such as clomiPRAMINE has resulted in serotonin syndrome. Additionally, the concomitant use of HYDROmorphone with anticholinergic drugs may increase the risk of urinary retention and severe constipation, which may lead to paralytic ileus. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments for serotonin syndrome and observe for signs and symptoms of urinary retention or reduced gastric motility. Discontinue HYDROmorphone if serotonin syndrome is suspected 321.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS depression; additive effects on gastric motility
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 213.
b) Serotonin syndrome symptoms such as neuromuscular abnormalities (including hyperreflexia, tremor, muscle rigidity, clonus, peripheral hypertonicity, and shivering), autonomic hyperactivity (including tachycardia, mydriasis, diaphoresis, the presence of bowel sounds, and diarrhea), and mental status changes (including agitation and delirium). Serotonin syndrome can be life-threatening. If serotonin syndrome develops, discontinue the offending agents and provide supportive care and other therapy as necessary 5.
Common questions
Can I take Clomipramine and Hydromorphone Injection together?
An increased risk of serotonin syndrome, an increased risk of CNS depression and an increased risk of paralytic ileus Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clomipramine and Hydromorphone Injection 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 Clomipramine or Hydromorphone Injection 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 (5)
- 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
- Product Information: ANAFRANIL(TM) oral capsules, clomipramine hydrochloride oral capsules. SpecGx LLC (per Dailymed), Webster Groves, MO, 2024. DailyMed
- Boyer EW & Shannon M: The serotonin syndrome. N Eng J Med 2005; 352(11):1112-1120. PubMed
Keep reading about Clomipramine
Keep reading about Hydromorphone Injection
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