Drug & supplement interaction

Dimethylsulfoxide (dmso) + diphenhydramine, calamine

diphenhydramine, calamine brand names: Caladryl cream, Caladryl lotion.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Dimethylsulfoxide (dmso) has a moderate interaction with diphenhydramine, calamine. Topical DMSO might increase the effects and adverse effects of topical drugs.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Dimethylsulfoxide (dmso) and diphenhydramine, calamine

Here is the interaction we found between these two, with the evidence behind it.

Moderate

TOPICAL DRUGS

Why this applies to diphenhydramine, calamine

diphenhydramine, calamine falls under TOPICAL DRUGS — the group Dimethylsulfoxide (dmso) interacts with.

Topical DMSO might increase the effects and adverse effects of topical drugs.
Evidence from animal studies and limited human studies suggests that DMSO may potentiate the action of numerous topical medications by increasing their absorption through the skin. This increase in absorption seems to depend on the concentration of DMSO and the molecular weight of the medication.
Severity Moderate Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the simple version: DMSO is a powerful skin penetrator. When you put it on the same area as a product like Caladryl (which contains diphenhydramine, an antihistamine, plus calamine), DMSO can act like a carrier and push more of that diphenhydramine through your skin and into your body than normally would get there.

Diphenhydramine is the same active ingredient in Benadryl, so absorbing extra can mean more drowsiness, dry mouth, dizziness, or grogginess than you'd expect from a topical product. There's another wrinkle: applying diphenhydramine over large or raw, broken skin (like a bad rash) already raises absorption, and DMSO could add to that. The evidence here is moderate and depends on the DMSO concentration. I'd just keep these two products on separate areas and check with your pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Jacob SW, Herschler R. Pharmacology of DMSO. Cryobiology 1986;23:14-27. PubMed
  2. Capriotti K, Capriotti JA. Dimethyl sulfoxide: history, chemistry, and clinical utility in dermatology. J Clin Aesthet Dermatol. 2012;5(9):24-6.
  3. DOMOSO SOLUTION (90% Dimethyl Sulfoxide). Fort Dodge Animal Health, Fort Dodge, Iowa. Avaliable at: https://www.zoetisus.com/_locale-assets/mcm-portal-assets/products/pdf/domoso_solution_pi.pdf. Accessed 8/3/2020.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Dimethylsulfoxide (dmso) Also Interacts With Other Medications

Dimethylsulfoxide (dmso) has 338 moderate known drug interactions in our database — the diphenhydramine, calamine one above is one of them. If you take anything else, check it against the full list below.

Moderate 338 No known interaction 2,492 (incl. diphenhydramine, calamine)
Taking anything else?

Check Another of Your Medications Against Dimethylsulfoxide (dmso)

Covers the 2,830 medications we’ve checked against Dimethylsulfoxide (dmso). Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With diphenhydramine, calamine

This page covers Dimethylsulfoxide (dmso) only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the diphenhydramine, calamine page lists 6 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Fever Bark (moderate), Iboga (moderate), Turpentine Oil (moderate), Yohimbe (moderate) and Alchemilla (minor).

By severity: 5 moderate · 1 minor.

From our pharmacist’s overview on the diphenhydramine, calamine page

“Yohimbe is the entry I would read first. Diphenhydramine, the itch-relieving antihistamine in Caladryl cream and lotion, blocks a liver enzyme called CYP2D6, and yohimbine, the active compound in yohimbe bark, needs that enzyme to leave the body, so its levels and side effects can climb.”

Reviewed by 2 · Jul 18, 2026

Open the diphenhydramine, calamine interaction page

How much people look this up

Where Dimethylsulfoxide (dmso) and diphenhydramine, calamine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Dimethylsulfoxide (dmso)
Top half

#645 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication diphenhydramine, calamine
Top 25%

#305 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Dimethylsulfoxide (dmso)

What is Dimethylsulfoxide (dmso)?

Dimethylsulfoxide (dmso)
  • Muscle and joint pain
  • Arthritis
  • Sprains and strains
  • Interstitial cystitis (bladder pain)
  • Skin penetration enhancer for other medicines

DMSO is a colorless liquid solvent that people apply to the skin for pain and inflammation, and it is FDA-approved (as a prescription) only for interstitial cystitis placed directly into the bladder. Most over-the-counter uses for pain and arthritis have limited or low-quality evidence, and DMSO can carry impurities or push other chemicals through your skin. Talk to your pharmacist or doctor before using it, and avoid industrial-grade products.

Read the full Dimethylsulfoxide (dmso) monograph & all interactions
Keep checking

Other Drugs & Dimethylsulfoxide (dmso)

Browse every other medication we’ve checked against Dimethylsulfoxide (dmso) — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
338Moderate
0Minor
2,491No known interaction
338 Moderate 2,491 No interaction
Moderate

338 interactions

Showing 60 of 338 moderate interactions — see all 338 on the Dimethylsulfoxide (dmso) page.

No interaction 2,491 drugs checked — show the list

We also checked Dimethylsulfoxide (dmso) against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,491 medications checked with no known interaction — see the full Dimethylsulfoxide (dmso) list.

See the full Dimethylsulfoxide (dmso) interactions page
See every supplement checked against diphenhydramine, calamine, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Dimethylsulfoxide (dmso) monograph › Uses, safety, and every drug interaction in one place diphenhydramine, calamine supplement interactions › Every supplement checked against diphenhydramine, calamine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Dimethylsulfoxide (dmso) and diphenhydramine, calamine Together: Common Questions

Can you take Dimethylsulfoxide (dmso) with diphenhydramine, calamine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Dimethylsulfoxide (dmso) and diphenhydramine, calamine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.