Drug & supplement interaction

Vitamin D + Hydrochlorothiazide, Losartan Potassium

Hydrochlorothiazide, Losartan Potassium brand name: Hyzaar.

Moderate Interaction
The bottom line Moderate

Hydrochlorothiazide, Losartan Potassium falls into 2 drug categories that Vitamin D can interact with; the most serious is rated moderate. Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Vitamin D and Hydrochlorothiazide, Losartan Potassium

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Vitamin D interacts with whole categories of medication. Hydrochlorothiazide, Losartan Potassium falls into 2 of those categories, so it can interact with Vitamin D in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

THIAZIDE DIURETICS

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Why this applies to Hydrochlorothiazide, Losartan Potassium

Hydrochlorothiazide, Losartan Potassium falls under THIAZIDE DIURETICS — the group Vitamin D interacts with.

Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily.
Severity Moderate Likelihood Probable Evidence D

Interaction 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..

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

Hyzaar is a combo pill, and the piece that matters here is the hydrochlorothiazide (a thiazide water pill). Thiazides tell your kidneys to hold onto more calcium instead of flushing it out. Vitamin D, on the other hand, helps your gut soak up more calcium from food. Put high-dose vitamin D and a thiazide together and, in theory, calcium can creep up too high (a state called hypercalcemia).

If that happens, you might feel nauseated, unusually thirsty, constipated, foggy-headed, or extra tired. To be fair, this is mostly based on scattered case reports, often in older folks also taking calcium supplements or antacids. Normal vitamin D doses are unlikely to cause trouble. Still, if you take both regularly, ask your pharmacist or doctor whether a calcium blood check makes sense before changing anything.

References
  1. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  2. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  3. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  4. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  5. Escribano, J., Balaguer, A., Pagone, F., Feliu, A., and Roque, I. Figuls. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane.Database.Syst.Rev. 2009;(1):CD004754. PubMed
Minor

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

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Hydrochlorothiazide, Losartan Potassium also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.
Severity Minor 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

Good news here: the worry about vitamin D and your blood pressure pill (Hyzaar, which is losartan plus hydrochlorothiazide) is pretty weak. The idea is that vitamin D might speed up a liver enzyme called CYP3A4, which could lower the amount of certain drugs floating in your blood. Losartan does get partly handled by that enzyme, so in theory it could become a touch less effective.

But honestly, this is just a lab and theory concern, not something seen as a real problem in people taking blood pressure medicine. I wouldn't expect your numbers to drift, and the water pill part isn't affected at all. Keep taking both as prescribed, and if you ever notice your blood pressure creeping up, mention it to your pharmacist or doctor.

References
  1. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  2. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54-8. 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

Vitamin D Also Interacts With Other Medications

Vitamin D has 79 moderate, 635 minor known drug interactions in our database — the Hydrochlorothiazide, Losartan Potassium one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Vitamin D

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

From our Q&A

Questions About Vitamin D or Hydrochlorothiazide, Losartan Potassium

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Vitamin D or Hydrochlorothiazide, Losartan Potassium, 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 Hydrochlorothiazide, Losartan Potassium

This page covers Vitamin D only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrochlorothiazide, Losartan Potassium page lists 314 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), Asarabacca (major) and Dolomite (major).

By severity: 12 major · 259 moderate · 43 minor.

From our pharmacist’s overview on the Hydrochlorothiazide, Losartan Potassium page

“Grapefruit is the everyday item to know first if you take hydrochlorothiazide with losartan (Hyzaar). It blocks the enzyme that clears losartan, raising drug levels, and it is one of 12 major-rated entries on a list of 314 supplements and herbs, enough serious risk to warrant genuine care.”

Reviewed by 2 · Jul 18, 2026

Open the Hydrochlorothiazide, Losartan Potassium interaction page

One more smart check

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

We hold 26,930 real supplement products containing Vitamin D, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Vitamin D. Your product may carry other ingredients that interact with Hydrochlorothiazide, Losartan Potassium too, on top of Vitamin D — 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 Vitamin D and Hydrochlorothiazide, Losartan Potassium 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 Vitamin D
Top 10

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

29 days ago today
Medication Hydrochlorothiazide, Losartan Potassium
Top 5%

#92 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 Vitamin D

What is Vitamin D?

Vitamin D
  • Bone health and osteoporosis
  • Correcting vitamin D deficiency
  • Immune system support
  • Muscle strength in older adults
  • General supplementation when sun exposure is low

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people, especially those with low sun exposure, benefit from supplementation, but more is not always better and very high doses can be harmful. Ask your pharmacist or doctor whether a blood test and supplement make sense for you.

Read the full Vitamin D monograph & all interactions
Keep checking

Other Drugs & Vitamin D

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

0Major
79Moderate
635Minor
2,115No known interaction
Moderate

79 interactions

Showing 60 of 79 moderate interactions — see all 79 on the Vitamin D page.

Minor

635 interactions

Showing 60 of 635 minor interactions — see all 635 on the Vitamin D page.

No interaction 2,115 drugs checked — show the list
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

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Pharmacist Counseling Corner

Taking Vitamin D and Hydrochlorothiazide, Losartan Potassium Together: Common Questions

Can you take Vitamin D with Hydrochlorothiazide, Losartan Potassium?
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.
Why are there 2 interactions listed for Vitamin D and Hydrochlorothiazide, Losartan Potassium?
Hydrochlorothiazide, Losartan Potassium belongs to more than one drug category, and Vitamin D interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Vitamin D and Hydrochlorothiazide, Losartan Potassium 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.