Drug & supplement interaction

Guarana + Mestranol, Norethindrone

Mestranol, Norethindrone brand names: Necon 1/50, Ortho Novum 21, Ortho-Novum 1/50-28, Norinyl 1 50 21 Day, Ortho Novum 1 Plus 50, and others.

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

Mestranol, Norethindrone falls into 2 drug categories that Guarana can interact with; the most serious is rated minor. Theoretically, concomitant use might increase the levels and adverse effects of caffeine.

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

Guarana and Mestranol, Norethindrone

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

Why Are There 2 Interactions?

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

Minor

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS

1 of 2

Why this applies to Mestranol, Norethindrone

Mestranol, Norethindrone falls under CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS — the group Guarana interacts with.

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 combo: it's really about the caffeine in guarana, not your birth control pill itself. The estrogen in your pill (mestranol, which converts to ethinyl estradiol) can mildly slow down the liver enzyme called CYP1A2, and that same enzyme is what clears caffeine from your body. So in theory, the caffeine from guarana might hang around a little longer and feel a bit stronger than usual.

What that could look like is the typical too-much-caffeine stuff: jitteriness, a racing or pounding heart, trouble sleeping, or feeling anxious. The good news is this is rated minor and is based only on lab-type reasoning, not real patient cases. If you notice you're more wired than normal, just ease up on the guarana and chat 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

2 of 2

Mestranol, 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 this combo: your birth control pill (the mestranol and norethindrone in Necon, Ortho-Novum, and similar brands) doesn't get changed by the guarana. It works the other way around. These pills slow 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 plain terms, you may feel more jittery, a racing or pounding heart, trouble sleeping, or anxiety from a smaller amount of guarana than usual. This is rated minor and is mostly theoretical, so it's not dangerous for most people. If you notice these effects, just ease up on the guarana, and check with your pharmacist if you have any heart or anxiety concerns.

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, 462 moderate, 184 minor known drug interactions in our database — the Mestranol, Norethindrone one above is among them. If you take anything else, check it against the full list below.

Major 8 Moderate 462 Minor 184 No known interaction 2,176 (incl. Mestranol, 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 Mestranol, Norethindrone

This page covers Guarana only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Mestranol, Norethindrone page lists 193 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 · 147 moderate · 40 minor.

Open the Mestranol, 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 Mestranol, 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 Mestranol, 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%

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

29 days ago today
Medication Mestranol, Norethindrone
Top 25%

#522 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
462Moderate
184Minor
2,175No known interaction
8 Major 462 Moderate 184 Minor 2,175 No interaction
Major

8 interactions

Moderate

462 interactions

Showing 60 of 462 moderate interactions — see all 462 on the Guarana page.

Minor

184 interactions

Showing 60 of 184 minor interactions — see all 184 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 Mestranol, 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 Mestranol, Norethindrone supplement interactions › Every supplement checked against Mestranol, 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 Mestranol, Norethindrone Together: Common Questions

Can you take Guarana with Mestranol, Norethindrone?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Guarana and Mestranol, Norethindrone?
Mestranol, 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 Mestranol, Norethindrone interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

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.