Drug & supplement interaction

Cola Nut + 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 Cola Nut can interact with; the most serious is rated moderate. Theoretically, CYP1A2 inhibitors might increase the levels and adverse effects of the caffeine in cola nut.

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

Cola Nut and Ethinyl Estradiol, Norethindrone

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

Why Are There 3 Interactions?

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

Moderate

CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS

1 of 3

Why this applies to Ethinyl Estradiol, Norethindrone

Ethinyl Estradiol, Norethindrone falls under CYTOCHROME P450 1A2 (CYP1A2) INHIBITORS — the group Cola Nut interacts with.

Theoretically, CYP1A2 inhibitors might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. Caffeine is metabolized by CYP1A2,.
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 thing to know about this pairing: it's really the caffeine in cola nut that gets affected, not your birth control. The estrogen part of your pill (ethinyl estradiol) can mildly slow down CYP1A2, the same liver enzyme that clears caffeine. So caffeine may hang around a bit longer than usual.

In plain terms, the cola nut may hit you harder. You might notice more jitteriness, a racing or pounding heart, trouble sleeping, or feeling on edge. Your pill keeps working normally for contraception or hormone therapy. This is a theoretical concern based on how the enzyme works, not strong human studies, so don't panic. If you feel wired or your heart races, ease up on caffeine and check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Weisburger JH. Tea and health: the underlying mechanisms. Proc Soc Exp Biol Med 1999;220:271-5. PubMed
  2. 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
  3. Carrillo JA, Benitez J. Clinically significant pharmacokinetic interactions between dietary caffeine and medications. Clin Pharmacokinet 2000;39:127-53. PubMed
  4. Kot, M. and Daniel, W. A. Effect of diethyldithiocarbamate (DDC) and ticlopidine on CYP1A2 activity and caffeine metabolism: an in vitro comparative study with human cDNA-expressed CYP1A2 and liver microsomes. Pharmacol Rep. 2009;61(6):1216-1220. PubMed
  5. Wojcikowski, J. and Daniel, W. A. Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism--an in vitro study. Pharmacol Rep. 2009;61(5):851-858. PubMed
  6. Wang, X. and Yeung, J. H. Effects of the aqueous extract from Salvia miltiorrhiza Bunge on caffeine pharmacokinetics and liver microsomal CYP1A2 activity in humans and rats. J Pharm Pharmacol 2010;62(8):1077-1083.
  7. Kot M, Daniel WA. Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep 2008;60:789-97.
  8. Kjaerstad MB, Nielsen F, Nohr-Jensen L, et al. Systemic uptake of miconazole during vaginal suppository use and effect on CYP1A2 and CYP3A4 associated enzyme activities in women. Eur J Clin Pharmacol 2010;66:1189-97. PubMed
  9. Goh BC, Reddy NJ, Dandamudi UB, et al. An evaluation of the drug interaction potential of pazopanib, an oral vascular endothelial growth factor receptor tyrosine kinase inhibitor, using a modified Cooperstown 5+1 cocktail in patients with advanced solid t
  10. Chen Y, Kang Z, Yan J, et al. Liu wei di huang wan, a well-known traditional Chinese medicine induces CYP1A2 while suppressing CYP2A6 and N-acetyltransferase 2 acivities in man. J Ethnopharmacol 2010;132:213-8.
  11. Suzuki S, Murayama Y, Sugiyama E, et al. Estimating pediatric doses of drugs metabolized by cytochrome P450 (CYP) isozymes, based on physiological liver development and serum protein levels. Yakugaku Zasshi 2010;130:613-20. PubMed
  12. Chien CF, Wu YT, Lee WC, et al. Herb-drug interaction of Andrographis paniculata extract and andrographolide on the pharmacokinetics of theophylline in rats. Chem Biol Interact 2010;184:458-65. PubMed
  13. Mills BM, Zaya MJ, Walters RR, et al. Current cytochrome P450 phenotyping methods applied to metabolic drug -drug interaction prediction in dogs. Drug Metab Dispos 2010;38:396-404. PubMed
  14. Turpault S, Brian W, Van Horn R, et al. Pharmacokinetic assessment of a five-probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6, and 3A. Br J Clin Pharmacol 2009;68:928-35. PubMed
  15. Filimonova AA, Ziganshina LE, Ziganshin AU, Chichirov AA. On the possibility of patient phenotyping on the basis of cytochrome p-450 1A2 isoenzyme activity using caffeine as the test substrate. Eksp Klin Farmakol 2009;72:61-5.
  16. Jenkins J, Williams D, Deng Y, et al. Eltrombopag, an oral thrombopoietin receptor agonist, has no impact on the pharmacokinetic profile of probe drugs for cytochrome P450 isoenzymes CYP3A4, CYP1A2, CYP2C9 and CYP2C19 in healthy men: a cocktail analysis.
  17. Perera, V., Gross, A. S., and McLachlan, A. J. Caffeine and paraxanthine HPLC assay for CYP1A2 phenotype assessment using saliva and plasma. Biomed.Chromatogr. 2010;24(10):1136-1144. PubMed
  18. Izzo, A. A. and Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009;69(13):1777-1798. PubMed
Moderate

ESTROGENS

2 of 3

Ethinyl Estradiol, Norethindrone also falls under ESTROGENS.

Theoretically, estrogens might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut 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 know about pairing cola nut with your birth control or hormone pill (the ethinyl estradiol part). Cola nut's main active ingredient is caffeine, and the estrogen in your pill can slow down how your body breaks caffeine down. The pill itself isn't harmed here. Instead, caffeine can hang around longer and hit a bit harder.

In practice, that may mean more jitteriness, a racing or pounding heart, trouble sleeping, or feeling on edge from a dose of cola nut that normally wouldn't bother you. This is a moderate, fairly likely interaction, but it's the kind of thing you can usually feel and adjust for. If you notice those effects, ease up on cola nut and other caffeine sources, and check in 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
Minor

CONTRACEPTIVE DRUGS

3 of 3

Ethinyl Estradiol, Norethindrone also falls under CONTRACEPTIVE DRUGS.

Theoretically, contraceptive drugs might increase the effects and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. Oral contraceptives can 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 a flip on what you might expect: it's actually your birth control pill (Loestrin, Ovcon, and similar combos of ethinyl estradiol and norethindrone) that affects the cola nut, not the other way around. The estrogen in these pills slows down how fast your body clears caffeine, by as much as 40 to 65 percent. Since cola nut's main active ingredient is caffeine, that caffeine can hang around longer and hit harder.

In real life, that may mean you feel more jittery, have a faster or pounding heartbeat, trouble sleeping, or a bit of an upset stomach from a smaller amount than usual. This is rated minor and is more of a comfort issue than a danger. If cola nut leaves you wired, just cut back, and check 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
  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

Cola Nut Also Interacts With Other Medications

Cola Nut has 546 moderate, 108 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.

Moderate 546 Minor 108 No known interaction 2,176 (incl. Ethinyl Estradiol, Norethindrone)
Taking anything else?

Check Another of Your Medications Against Cola Nut

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

Everything else you take

See Every Supplement That Interacts With Ethinyl Estradiol, Norethindrone

This page covers Cola Nut 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 Cola Nut as Part of a Dietary Supplement Product? Check It for Interactions

We hold 2 real supplement products containing Cola Nut, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Cola Nut. Your product may carry other ingredients that interact with Ethinyl Estradiol, Norethindrone too, on top of Cola Nut — 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 Cola Nut 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 Cola Nut
Steady interest

#1,047 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Ethinyl Estradiol, Norethindrone
Top 25%

#450 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 Cola Nut

What is Cola Nut?

Cola Nut
  • Energy and alertness
  • Mental focus
  • Physical performance
  • Weight loss support
  • Traditional digestive aid

Cola nut is a caffeine-containing seed from West Africa used mainly as a natural stimulant for energy and alertness. Most of its effects come from caffeine, and strong human evidence for specific health benefits is limited. Because of its caffeine content, people sensitive to stimulants and those who are pregnant or have heart conditions should be cautious.

Read the full Cola Nut monograph & all interactions
Keep checking

Other Drugs & Cola Nut

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

0Major
546Moderate
108Minor
2,175No known interaction
546 Moderate 108 Minor 2,175 No interaction
Moderate

546 interactions

Showing 60 of 546 moderate interactions — see all 546 on the Cola Nut page.

Minor

108 interactions

Showing 60 of 108 minor interactions — see all 108 on the Cola Nut page.

No interaction 2,175 drugs checked — show the list

We also checked Cola Nut 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 Cola Nut list.

See the full Cola Nut 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
Cola Nut 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 Cola Nut and Ethinyl Estradiol, Norethindrone Together: Common Questions

Can you take Cola Nut 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 Cola Nut and Ethinyl Estradiol, Norethindrone?
Ethinyl Estradiol, Norethindrone belongs to more than one drug category, and Cola Nut 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 Cola Nut 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.