Drug Interaction Report

Calcium Oxybate and Diphenhydramine Injection: Interaction Details

A pharmacist-reviewed analysis of the Calcium Oxybate and Diphenhydramine 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

Calcium Oxybate

Xywav
+

Diphenhydramine Injection

Banophen Benadryl Calagel Reformulated Jun 2019 Compoz Dermamycin Diphedryl Diphenhist Dormin
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
Contraindicated
These should generally not be used together.
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 25 documented Calcium Oxybate interactions, 2 are rated contraindicated — 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
Contraindicated

What happens

An increased risk of CNS depression and clinically significant respiratory depression, obtundation, hypotension, profound sedation, syncope, and death

Interaction Deep Dive

Concomitant use of sodium oxybate or mixed oxybate salts and sedative hypnotics is contraindicated because of the risk for additive CNS depression and clinically significant respiratory depression, obtundation, hypotension, profound sedation, syncope, and death123.

Why it happens (mechanism)

Additive CNS depression

Common questions

Can I take Calcium Oxybate and Diphenhydramine Injection together?

An increased risk of CNS depression and clinically significant respiratory depression, obtundation, hypotension, profound sedation, syncope, and death Always confirm with your pharmacist or prescriber before making any change.

How serious is the Calcium Oxybate and Diphenhydramine Injection interaction?

It is rated contraindicated. These should generally not be used together.

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 Calcium Oxybate or Diphenhydramine 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 (3)

  1. Product Information: XYWAV(R) oral solution, calcium, magnesium, potassium, sodium oxybates oral solution. Jazz Pharmaceuticals Inc (per manufacturer), Palo Alto, CA, 2023. DailyMed
  2. Product Information: XYREM(R) oral solution, sodium oxybate oral solution. Jazz Pharmaceuticals Inc (per manufacturer), Palo Alto, CA, 2023. DailyMed
  3. Product Information: LUMRYZ(TM) oral extended-release suspension, sodium oxybate extended-release suspension. Avadel CNS Phamaceuticals LLC (per FDA), Chesterfield, MO, 2024. DailyMed
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Calcium Oxybate

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Diphenhydramine Injection

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All Diphenhydramine Injection interactions (123) Diphenhydramine Injection drug information
Also serious with: Potassium Citrate Potassium Chloride Magnesium Oxybate Isocarboxazid

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