Drug & supplement interaction

Guarana + Drospirenone, Estetrol

Drospirenone, Estetrol brand name: Nextstellis.

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

Drospirenone, Estetrol falls into 3 drug categories that Guarana can interact with; the most serious is rated moderate. Theoretically, estrogens might increase the levels and adverse effects of caffeine.

Read the full interaction report
SeverityModerate
LikelihoodProbable
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Guarana and Drospirenone, Estetrol

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Guarana interacts with whole categories of medication. Drospirenone, Estetrol falls into 3 of those categories, so it can interact with Guarana in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

ESTROGENS

1 of 3

Why this applies to Drospirenone, Estetrol

Drospirenone, Estetrol falls under ESTROGENS — the group Guarana interacts with.

Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Guarana contains caffeine. Estrogen inhibits caffeine metabolism.
Severity Moderate Likelihood Probable Evidence B

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

Here's the thing to keep in mind with Nextstellis (drospirenone and estetrol) and guarana: this works the opposite of what you might expect. Your birth control pill isn't really affected here. Instead, the estrogen part (estetrol) slows down how your body clears caffeine, and guarana is basically concentrated caffeine. So the caffeine can hang around longer and hit harder than it normally would.

In real life that can mean more jitteriness, a racing or pounding heart, trouble sleeping, anxiety, or an upset stomach. This is rated probable but the effect size is modest, so a normal cup of coffee usually isn't a big deal. Higher-dose guarana supplements are where it adds up. If you notice you're more wired than usual, ease off and chat with your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS

2 of 3

Drospirenone, Estetrol also falls under CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS.

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Guarana contains caffeine. Caffeine is metabolized by the CYP1A2 enzyme. Theoretically, drugs that inhibit CYP1A2 may decrease the rate of caffeine clearance and increase caffeine levels.
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

Here's the thing to notice: in this pairing it's the guarana that gets affected, not your birth control pill. Nextstellis (drospirenone and estetrol) can mildly slow down the CYP1A2 enzyme, and that's the same enzyme your body uses to clear caffeine. So the caffeine in guarana may hang around a little longer and pile up, which can mean more jitteriness, a faster heartbeat, trouble sleeping, or feeling on edge.

This one is gentle and only theoretical, based on lab data rather than real-world reports, so most people won't notice much. Your pill keeps working just fine. If you're sensitive to caffeine or already feel wired, go easy on guarana and check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hagg S, Spigset O, Mjorndal T, Dahlqvist R. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2000;49:59-63. PubMed
  2. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
Minor

CONTRACEPTIVE DRUGS

3 of 3

Drospirenone, Estetrol also falls under CONTRACEPTIVE DRUGS.

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in guarana.
Guarana contains caffeine. Oral contraceptives decrease the rate of caffeine clearance by 40% to 65%.
Severity Minor 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 gist for Nextstellis (drospirenone and estetrol) taken with guarana. Guarana is basically a concentrated source of caffeine. Birth control pills like this one slow down how fast your body clears caffeine, by roughly 40 to 65 percent. So the caffeine from guarana can hang around longer and hit harder than you'd expect.

What that looks like in real life: more jitters, a racing or pounding heart, trouble sleeping, and feeling anxious or wired. This is a minor, mostly theoretical concern, and it doesn't make your birth control work any less. Your pill itself isn't being changed. If you notice you're more sensitive to caffeine since starting it, just ease up on guarana and check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. J Clin Pharmacol 1999;39:936-40. PubMed
  2. Abernethy DR, Todd EL. Impairment of caffeine clearance by chronic use of low-dose oestrogen-containing oral contraceptives. Eur J Clin Pharmacol 1985;28:425-8. 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

Guarana Also Interacts With Other Medications

Guarana has 8 major, 461 moderate, 185 minor known drug interactions in our database — the Drospirenone, Estetrol one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 461 Minor 185 No known interaction 2,176 (incl. Drospirenone, Estetrol)
Taking anything else?

Check Another of Your Medications Against Guarana

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

Everything else you take

See Every Supplement That Interacts With Drospirenone, Estetrol

This page covers Guarana only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Drospirenone, Estetrol page lists 245 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Beer (major), Grapefruit (major), Siberian Cocklebur (major) and St. John's Wort (major).

By severity: 6 major · 200 moderate · 39 minor.

From our pharmacist’s overview on the Drospirenone, Estetrol page

“The stakes with Nextstellis (drospirenone and estetrol) are the ones that come with any birth control pill, because an interaction that lowers its hormone levels can mean an unplanned pregnancy, and I would treat this list with genuine seriousness. Most of what is here changes how the body handles the hormones.”

Reviewed by 2 · Jul 18, 2026

Open the Drospirenone, Estetrol interaction page

One more smart check

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

We hold 1,430 real supplement products containing Guarana, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Guarana. Your product may carry other ingredients that interact with Drospirenone, Estetrol too, on top of Guarana — 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 Guarana and Drospirenone, Estetrol 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 Guarana
Top 10%

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

29 days ago today
Medication Drospirenone, Estetrol
Top half

#1,224 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 Guarana

What is Guarana?

Guarana
  • Energy and alertness
  • Reducing fatigue
  • Weight loss support
  • Athletic performance
  • Mental focus

Guarana is an Amazonian seed that is naturally high in caffeine, which explains most of its stimulant and energy effects. While it may give a short-term boost in alertness and reduce fatigue, strong evidence for weight loss or major performance gains is limited, and it carries the same risks as too much caffeine. Talk to your pharmacist or doctor before using it, especially if you have heart problems, anxiety, or are pregnant.

Read the full Guarana monograph & all interactions
Keep checking

Other Drugs & Guarana

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

8Major
461Moderate
185Minor
2,175No known interaction
8 Major 461 Moderate 185 Minor 2,175 No interaction
Major

8 interactions

Moderate

461 interactions

Showing 60 of 461 moderate interactions — see all 461 on the Guarana page.

Minor

185 interactions

Showing 60 of 185 minor interactions — see all 185 on the Guarana page.

No interaction 2,175 drugs checked — show the list

We also checked Guarana 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 Guarana list.

See the full Guarana interactions page
See every supplement checked against Drospirenone, Estetrol, 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
Guarana monograph › Uses, safety, and every drug interaction in one place Drospirenone, Estetrol supplement interactions › Every supplement checked against Drospirenone, Estetrol, 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 Guarana and Drospirenone, Estetrol Together: Common Questions

Can you take Guarana with Drospirenone, Estetrol?
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 3 interactions listed for Guarana and Drospirenone, Estetrol?
Drospirenone, Estetrol belongs to more than one drug category, and Guarana 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 Guarana and Drospirenone, Estetrol 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.