Drug Interaction Report

Spironolactone and Morphine Injection: Interaction Details

A pharmacist-reviewed analysis of the Spironolactone and Morphine Injection 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

Spironolactone

Aldactone Carospir
+

Morphine Injection

Astramorph® PF Duramorph Duramorph® Infumorph Infumorph® Kadian Mitigo MS Contin
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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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 71 documented Spironolactone interactions, 60 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 morphine exposure, an increased risk of morphine-related adverse effects (hypotension, respiratory depression, profound sedation, coma) and an reduced spironolactone efficacy

Interaction Deep Dive

Coadministration of morphine, which may induce antidiuretic hormone release, and spironolactone (diuretic agent) may result in reduced efficacy of the diuretic. Additionally, concomitant use of morphine and spironolactone (P-gp inhibitor) may increase the exposure of morphine by two-fold and increase the risk of adverse effects CNS depression. If coadministration is required, monitor for signs of CNS depression. Evaluate patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of morphine and/or spironolactone as necessary. Also, evaluate patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the spironolactone as needed15432.

Why it happens (mechanism)

Inhibition of P-gp-mediated efflux transport of spironolactone; induction of antidiuretic hormone release

Common questions

Can I take Spironolactone and Morphine Injection together?

Increased morphine exposure, an increased risk of morphine-related adverse effects (hypotension, respiratory depression, profound sedation, coma) and an reduced spironolactone efficacy Always confirm with your pharmacist or prescriber before making any change.

How serious is the Spironolactone and Morphine 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.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Spironolactone or Morphine 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)

  1. Product Information: MS CONTIN(R) oral extended-release tablets, morphine sulfate oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
  2. Product Information: INFUMORPH intrathecal, epidural injection, morphine sulfate intrathecal, epidural injection. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley Heights, NJ, 2023. DailyMed
  3. Product Information: Morphine sulfate oral solution, morphine sulfate oral solution. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley Heights, NJ, 2023. DailyMed
  4. Product Information: DURAMORPH intravenous, epidural, intrathecal injection, morphine sulfate intravenous, epidural, intrathecal injection. Hikma Pharmaceuticals USA Inc (Per FDA), Berkeley, NJ, 2023. DailyMed
  5. Product Information: KADIAN(R) oral extended-release capsules, morphine sulfate oral extended-release capsules. Allergan USA, Inc (per FDA), Madison, NJ, 2019. DailyMed
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Spironolactone

Keep reading about Spironolactone

All Spironolactone interactions (71)
Also serious with: Colchicine Aspirin Perindopril Enoxaparin Injection
Morphine Injection

Keep reading about Morphine Injection

All Morphine Injection interactions (437) Morphine Injection drug information
Also serious with: Rasagiline Procarbazine Phenelzine Ozanimod
Beyond drug–drug

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:

Spironolactone + Activated Charcoal American Hellebore American Mistletoe Lithium Oleander Tyramine Yellow Dock Abuta + 198 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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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.