Drug Interaction Report

Hydromorphone Rectal and Benzhydrocodone: Interaction Details

A pharmacist-reviewed analysis of the Hydromorphone Rectal and Benzhydrocodone interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Benzhydrocodone

No brand names on record
+

Hydromorphone Rectal

available generically
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
LinkedIn
Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 344 documented Hydromorphone Rectal interactions, 329 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome

Interaction Deep Dive

Avoid concomitant use of opioid cough medication formulations and CNS depressants1. Also, concomitant use of HYDROcodone, with serotonergic drugs has resulted in serotonin syndrome. Reserve the concomitant use of non-cough HYDROcodone products 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 HYDROcodone or the CNS depressant and closely monitor for sedation, respiratory depression, and signs and symptoms of serotonin syndrome. Discontinue HYDROcodone if serotonin syndrome is suspected 234. 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 56.

Why it happens (mechanism)

Additive CNS depression; additive serotonergic effects

Literature reports

1 report — tap to read

a) Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs 56.

Common questions

Can I take Hydromorphone Rectal and Benzhydrocodone 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 Hydromorphone Rectal and Benzhydrocodone 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 Hydromorphone Rectal or Benzhydrocodone 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 (6)

  1. Product Information: VITUZ(R) oral solution, hydrocodone bitartrate chlorpheniramine maleate oral solution. Hawthorn Pharmaceuticals, Inc. (per FDA), Morristown, NJ, 2017.
  2. Product Information: ZOHYDRO(R) ER oral extended-release capsules, hydrocodone bitartrate oral extended-release capsules. Pernix Therapeutics, LLC. (per FDA), Morristown, NJ, 2016. DailyMed
  3. Product Information: NORCO 5/325 oral tablets, hydrocodone bitartrate acetaminophen oral tablets. Allergan USA, Inc. (per DailyMed), Irvine, CA, 2016.
  4. Product Information: VANTRELA(TM) ER oral extended-release tablets, hydrocodone bitartrate oral extended-release tablets. Teva Pharmaceuticals USA, Inc (per manufacturer), North Wales, PA, 2017. DailyMed
  5. Product Information: HYSINGLA(R) ER oral extended-release tablets, hydrocodone bitartrate oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
  6. Product Information: APADAZ(R) oral tablets, benzhydrocodone acetaminophen oral tablets. Zevra Therapeutics, Inc. (per FDA), Celebration, FL, 2023. DailyMed
Was this write-up helpful?
Benzhydrocodone

Keep reading about Benzhydrocodone

All Benzhydrocodone interactions (56)
Also serious with: Acetaminophen And Codeine Abametapir Trospium / Xanomeline Morphine Injection
Hydromorphone Rectal

Keep reading about Hydromorphone Rectal

All Hydromorphone Rectal interactions (344) Hydromorphone Rectal drug information
Also serious with: Isocarboxazid Naltrexone Phenelzine Tranylcypromine

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

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
This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.