Drug & supplement interaction

Guarana + Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone brand names: Femhrt, Loestrin 21, Ovcon 35 21, Ovcon 50 28, Necon 0.5 35 21, and others.

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

Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone

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. Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone 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 a twist worth knowing: this interaction is really about what your birth control pill (which contains the estrogen ethinyl estradiol) does to the caffeine in guarana, not the other way around. Estrogen can slow down how your liver clears caffeine, so the caffeine tends to hang around longer in your body.

In plain terms, a guarana energy product may hit you harder and last longer than expected. That can mean a racing or pounding heart, jitters, feeling anxious, an upset stomach, or trouble sleeping. Your pill keeps working fine, so this isn't about losing protection. If you notice you're more sensitive to caffeine, it may help to cut back on guarana or have it earlier in the day. Chat with your pharmacist if you're unsure.

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

Ethinyl Estradiol, Norethindrone 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 understand about this pairing: it's really about the caffeine in guarana, not your birth control pill. The estrogen part of your pill (ethinyl estradiol) can gently slow down the liver enzyme (CYP1A2) that clears caffeine from your body. So when you take guarana on top of it, that caffeine may hang around a little longer than usual.

In plain terms, you might feel more of the typical caffeine effects: a faster heartbeat, jitteriness, trouble sleeping, or some anxiety. Your pill keeps working fine for birth control or hormone purposes. This is a minor, mostly theoretical concern based on lab data, so most people won't notice much. If you feel wired or shaky, ease up on the guarana and chat with your pharmacist.

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

Ethinyl Estradiol, Norethindrone 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 thing to know about pairing guarana with your birth control pill (the ethinyl estradiol and norethindrone combo). It's actually the pill affecting the guarana, not the other way around. The estrogen in your pill slows down how fast your body clears caffeine, by roughly 40 to 65 percent. Since guarana is basically a concentrated caffeine source, that caffeine can hang around longer and hit harder than you'd expect.

In real life, that might mean more jitteriness, a racing heart, trouble sleeping, or feeling anxious or shaky. This is a minor interaction and it won't make your birth control less effective. If you notice caffeine bothering you more than usual, just ease back on the guarana, and chat with your pharmacist if you have questions.

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 Ethinyl Estradiol, Norethindrone 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. Ethinyl Estradiol, Norethindrone)
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 Ethinyl Estradiol, Norethindrone

This page covers Guarana only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Norethindrone page lists 240 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 · 196 moderate · 38 minor.

From our pharmacist’s overview on the Ethinyl Estradiol, Norethindrone page

“If you take a birth control pill or hormone therapy containing ethinyl estradiol and norethindrone (Loestrin, Femhrt, and others), a few supplements can genuinely undermine it, so read this page with care. Six of the 240 ingredients on file are rated major, and those six come first.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone
Top 10%

#237 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 Ethinyl Estradiol, Norethindrone, 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 Ethinyl Estradiol, Norethindrone supplement interactions › Every supplement checked against Ethinyl Estradiol, Norethindrone, 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 Ethinyl Estradiol, Norethindrone Together: Common Questions

Can you take Guarana with Ethinyl Estradiol, Norethindrone?
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 Ethinyl Estradiol, Norethindrone?
Ethinyl Estradiol, Norethindrone 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 Ethinyl Estradiol, Norethindrone 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.