Drug & supplement interaction

Hesperidin + Riociguat

Riociguat brand name: Adempas.

Moderate Interaction
The bottom line Moderate

Riociguat falls into 2 drug categories that Hesperidin can interact with; the most serious is rated moderate. Theoretically, taking hesperidin with antihypertensive drugs might increase the risk of hypotension.

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

Hesperidin and Riociguat

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

Why Are There 2 Interactions?

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

Moderate

ANTIHYPERTENSIVE DRUGS

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Why this applies to Riociguat

Riociguat falls under ANTIHYPERTENSIVE DRUGS — the group Hesperidin interacts with.

Theoretically, taking hesperidin with antihypertensive drugs might increase the risk of hypotension.
Some clinical and animal research shows that hesperidin can decrease blood pressure. However, other clinical research shows that hesperidin does not affect blood pressure.
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: Riociguat (Adempas) already lowers blood pressure by relaxing your blood vessels. Hesperidin, a citrus flavonoid found in vein-health supplements, might nudge blood pressure down a little too. Stack the two and, in theory, your pressure could drop a bit more than expected. That could leave you feeling lightheaded or dizzy, especially when you stand up quickly, and it might bring on headache or even fainting.

The good news: this concern is theoretical, based on how these things work, not on strong human studies. In fact, some research shows hesperidin doesn't change blood pressure at all. Small amounts from eating oranges almost certainly won't matter; concentrated supplements are the question mark. Please don't start or stop anything on your own. Just give your pharmacist or doctor a heads-up so they can watch your blood pressure.

References
  1. Yamamoto, M., Suzuki, A., Jokura, H., Yamamoto, N., and Hase, T. Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in spontaneously hypertensive rats. Nutrition 2008;24(5):470-476. PubMed
  2. Morand C, Dubray C, Milenkovic D, et al. Hesperidin contributes to the vascular protective effects of orange juice: a randomized crossover study in healthy volunteers. Am J Clin Nutr 2011;93(1):73-80. PubMed
  3. Homayouni F, Haidari F, Hedayati M, Zakerkish M, Ahmadi K. Blood pressure lowering and anti-inflammatory effects of hesperidin in type 2 diabetes; a randomized double-blind controlled clinical trial. Phytother Res. 2018;32(6):1073-1079. PubMed
  4. Mohammadi M, Ramezani-Jolfaie N, Lorzadeh E, Khoshbakht Y, Salehi-Abargouei A. Hesperidin, a major flavonoid in orange juice, might not affect lipid profile and blood pressure: A systematic review and meta-analysis of randomized controlled clinical trials PubMed
  5. Valls RM, Pedret A, Calderón-Pérez L, et al. Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study). Eur J Nutr. 2021;60(3):1277-1288. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

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Riociguat also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, hesperidin might inhibit P-glycoprotein-mediated drug efflux and potentially increase levels of drugs that are substrates of P-glycoprotein.
In vitro research shows that hesperidin can inhibit P-glycoprotein efflux. This effect has not been reported in humans.
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 gist: your body uses a kind of cellular bouncer called P-glycoprotein to push certain drugs back out, and riociguat (Adempas) is one of the medicines that protein helps move along. In lab dishes, hesperidin has been shown to slow that bouncer down. If that happened in people, a bit more riociguat could stay in your system, which might nudge its blood-pressure-lowering effect a little stronger.

With riociguat, stronger effects could mean dizziness, lightheadedness, headache, low blood pressure, or feeling faint, especially when standing up. The important part: this is only seen in test tubes so far, never confirmed in humans, so I wouldn't panic. Concentrated hesperidin supplements are more of a question than the bit you get from eating an orange. Just loop in your pharmacist or doctor before adding it.

References
  1. El-Readi, M. Z., Hamdan, D., Farrag, N., El-Shazly, A., and Wink, M. Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from Citrus species in human colon and leukaemia cell lines. Eur.J.Pharmacol. 1-25-2010;626(2-3):139-145 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

Hesperidin Also Interacts With Other Medications

Hesperidin has 701 moderate known drug interactions in our database — the Riociguat 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 Hesperidin

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

Everything else you take

See Every Supplement That Interacts With Riociguat

This page covers Hesperidin only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Riociguat page lists 230 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), Grapefruit (major) and St. John's Wort (major).

By severity: 6 major · 187 moderate · 37 minor.

From our pharmacist’s overview on the Riociguat page

“Riociguat (Adempas) works by relaxing the blood vessels in your lungs, which also lowers blood pressure, so I read this list of 230 supplements and herbs with real concern, and the six rated major are what to understand first. Grapefruit can push riociguat levels up and intensify its effect, while St.”

Reviewed by 2 · Jul 18, 2026

Open the Riociguat interaction page

One more smart check

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

We hold 1,895 real supplement products containing Hesperidin, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Hesperidin. Your product may carry other ingredients that interact with Riociguat too, on top of Hesperidin — 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 Hesperidin and Riociguat 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 Hesperidin
Top 25%

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

29 days ago today
Medication Riociguat
Steady interest

#1,598 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 Hesperidin

What is Hesperidin?

Hesperidin
  • Hemorrhoids
  • Varicose veins and poor circulation
  • Leg swelling (venous insufficiency)
  • High blood pressure
  • Antioxidant support

Hesperidin is a flavonoid found in citrus fruits that is often combined with diosmin and used for vein and circulation problems like hemorrhoids and varicose veins. Some evidence supports these uses, but data for many other claims is limited. It is generally well tolerated, but pregnant and breastfeeding people should avoid it because safety has not been established.

Read the full Hesperidin monograph & all interactions
Medication

About Riociguat

What Is Riociguat Used For?

Brand name: Adempas

Riociguat tablets — sold as Adempas and under the generic name Riociguat — are used to treat adults with two types of pulmonary hypertension (high blood pressure in the lungs).

The first is chronic thromboembolic pulmonary hypertension (CTEPH), a condition caused by blood clots in the lung arteries, either after surgery or when surgery is not an option. The second is pulmonary arterial hypertension (PAH), where the arteries carrying blood to the lungs are narrowed or blocked. In both conditions, riociguat helps improve exercise ability and functional status, and in PAH it also helps slow the disease from getting worse.

See full Riociguat drug information
Keep checking

Other Drugs & Hesperidin

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

0Major
701Moderate
0Minor
2,128No known interaction
Moderate

701 interactions

Showing 60 of 701 moderate interactions — see all 701 on the Hesperidin page.

No interaction 2,128 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 Hesperidin and Riociguat Together: Common Questions

Can you take Hesperidin with Riociguat?
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 Hesperidin and Riociguat?
Riociguat belongs to more than one drug category, and Hesperidin 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 Hesperidin and Riociguat 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.