Drug & supplement interaction

Caffeine + Metolazone

Metolazone brand names: Diulo, Zaroxolyn, Mykrox.

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

Caffeine has a moderate interaction with Metolazone. Theoretically, using caffeine with diuretic drugs might increase the risk of hypokalemia.

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

Caffeine and Metolazone

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

Moderate

DIURETIC DRUGS

Why this applies to Metolazone

Metolazone falls under DIURETIC DRUGS — the group Caffeine interacts with.

Theoretically, using caffeine with diuretic drugs might increase the risk of hypokalemia.
Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump. Diuretics can also cause lower potassium levels.
Severity Moderate Likelihood Possible Evidence D

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. Metolazone is a water pill that helps your body get rid of extra salt and fluid, but one of its known side effects is that it can lower your potassium level. Caffeine, especially in larger amounts, may also nudge potassium a little lower. So in theory, pairing the two could make low potassium (called hypokalemia) a bit more likely.

I want to be honest about the evidence here: this is mostly based on how these things work on paper, not strong studies, so it's a possible concern rather than a sure thing. A normal cup or two of coffee or tea probably won't be a problem for most people. Where I'd pay attention is heavy caffeine use, like energy drinks or lots of strong coffee. Low potassium can cause muscle cramps, weakness, or an irregular heartbeat. Don't change anything on your own. Just ask your doctor or pharmacist whether your potassium should be checked.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Norager, C. B., Jensen, M. B., Weimann, A., and Madsen, M. R. Metabolic effects of caffeine ingestion and physical work in 75-year old citizens. A randomized, double-blind, placebo-controlled, cross-over study. Clin Endocrinol (Oxf) 2006;65(2):223-228. PubMed
  2. Simmonds, M. J., Minahan, C. L., and Sabapathy, S. Caffeine improves supramaximal cycling but not the rate of anaerobic energy release. Eur.J Appl Physiol 2010;109(2):287-295. PubMed
  3. Rigato, I., Blarasin, L., and Kette, F. Severe hypokalemia in 2 young bicycle riders due to massive caffeine intake. Clin J Sport Med. 2010;20(2):128-130. PubMed
  4. Ernest, D., Chia, M., and Corallo, C. E. Profound hypokalaemia due to Nurofen Plus and Red Bull misuse. Crit Care Resusc. 2010;12(2):109-110. DOI
  5. Clausen, T. Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam.Clin Pharmacol 2010;24(5):595-605. PubMed

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

Caffeine Also Interacts With Other Medications

Caffeine has 8 major, 482 moderate, 164 minor known drug interactions in our database — the Metolazone one above is one of them. If you take anything else, check it against the full list below.

Major 8 Moderate 482 Minor 164 No known interaction 2,176 (incl. Metolazone)
Taking anything else?

Check Another of Your Medications Against Caffeine

Covers the 2,830 medications we’ve checked against Caffeine. Pick one to open its full report.

From our Q&A

Questions About Caffeine or Metolazone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Caffeine or Metolazone, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Metolazone

This page covers Caffeine only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Metolazone page lists 222 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Dolomite (major) and Lithium (major).

By severity: 8 major · 190 moderate · 24 minor.

Open the Metolazone interaction page

One more smart check

Taking Caffeine as Part of a Dietary Supplement Product? Check It for Interactions

We hold 6,775 real supplement products containing Caffeine, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Caffeine. Your product may carry other ingredients that interact with Metolazone too, on top of Caffeine — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Caffeine and Metolazone 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 Caffeine
Top 5%

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

29 days ago today
Medication Metolazone
Top 25%

#634 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 Caffeine

What is Caffeine?

  • Mental alertness and reducing fatigue
  • Improving athletic performance
  • Headache and migraine relief
  • Boosting focus and concentration
  • Weight loss aid

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too much can cause jitteriness, a racing heart, and sleep problems. Pregnant women and people with heart conditions or anxiety should be especially careful and check with a doctor or pharmacist.

Read the full Caffeine monograph & all interactions
Medication

About Metolazone

What Is Metolazone Used For?

Brand names: Diulo, Zaroxolyn, Mykrox

Metolazone tablets help your body get rid of extra salt and water. They are used for swelling (edema) caused by heart failure and by kidney diseases, including nephrotic syndrome and reduced kidney function.

They are also used to treat high blood pressure, either alone or with other blood pressure medicines from a different class. Mykrox tablets, a faster-acting form of metolazone, are meant for new patients with mild to moderate high blood pressure.

See full Metolazone drug information
Keep checking

Other Drugs & Caffeine

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

8Major
482Moderate
164Minor
2,175No known interaction
8 Major 482 Moderate 164 Minor 2,175 No interaction
Major

8 interactions

Moderate

482 interactions

Showing 60 of 482 moderate interactions — see all 482 on the Caffeine page.

Minor

164 interactions

Showing 60 of 164 minor interactions — see all 164 on the Caffeine page.

No interaction 2,175 drugs checked — show the list

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

Showing the 60 most looked-up of 2,175 medications checked with no known interaction — see the full Caffeine list.

See the full Caffeine interactions page
See every supplement checked against Metolazone, 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
Caffeine monograph › Uses, safety, and every drug interaction in one place Metolazone supplement interactions › Every supplement checked against Metolazone, ranked by severity Metolazone drug information › The full plain-English guide to this medication 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 Caffeine and Metolazone Together: Common Questions

Can you take Caffeine with Metolazone?
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 Caffeine and Metolazone 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

Still Have a Question About Metolazone and Caffeine?

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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.