Drug & supplement interaction

Bulbine Natalensis + Ethinyl estradiol, Levonogestrel

Ethinyl estradiol, Levonogestrel brand name: Lybrel.

Moderate Interaction
The bottom line Moderate

Ethinyl estradiol, Levonogestrel falls into 3 drug categories that Bulbine Natalensis can interact with; the most serious is rated moderate. Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.

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

Bulbine Natalensis and Ethinyl estradiol, Levonogestrel

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

Why Are There 3 Interactions?

Bulbine Natalensis interacts with whole categories of medication. Ethinyl estradiol, Levonogestrel falls into 3 of those categories, so it can interact with Bulbine Natalensis 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) SUBSTRATES

1 of 3

Why this applies to Ethinyl estradiol, Levonogestrel

Ethinyl estradiol, Levonogestrel falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Bulbine Natalensis interacts with.

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that Bulbine natalensis stem extract slightly induces CYP1A2 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP1A2 substrates; however, this has not been studied 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 quick version for your birth control pill (Lybrel, which is ethinyl estradiol plus levonorgestrel). In lab dishes, Bulbine natalensis seemed to slightly speed up an enzyme called CYP1A2, one of the helpers your body uses to break down estrogen. If that happened in real people, your body might clear the hormones a little faster, which could in theory lower the protection and lead to breakthrough bleeding or spotting, or even a higher chance of an unplanned pregnancy.

That said, this is only a theory from test-tube research, never confirmed in humans, so I wouldn't lose sleep over it. Because your pill works best at steady levels, I'd still mention this combo to your pharmacist or doctor before starting Bulbine, especially since this supplement also raises liver and kidney concerns.

References
  1. Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Ethinyl estradiol, Levonogestrel also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that Bulbine natalensis stem extract induces CYP3A4 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP3A4 substrates, but this has not been studied 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 concern with pairing Lybrel (a birth control pill containing ethinyl estradiol and levonorgestrel) with Bulbine natalensis. Your body clears these hormones partly through a liver enzyme called CYP3A4. Lab studies suggest Bulbine may rev that enzyme up (induce it), which could mean your body breaks down the hormones faster and keeps less of them around.

For a birth control pill, lower hormone levels can mean weaker protection against pregnancy and more breakthrough bleeding or spotting. I want to be honest, though: this is only a theoretical worry based on test-tube research, with nothing proven in people. Because an unplanned pregnancy is a big deal, I'd still talk with your pharmacist or doctor before combining them, and ask about a backup method just in case.

References
  1. Husain I, Dale OR, Manda V, et al. Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp. Planta Med 2022;88(12):975-984. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

3 of 3

Ethinyl estradiol, Levonogestrel also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, Bulbine natalensis stem might increase the levels and clinical effects of p-glycoprotein substrates.
In vitro research shows that Bulbine natalensis stem extract induces p-glycoprotein mRNA expression; however, effects on transporter expression were not evaluated.
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 short version on combining Bulbine natalensis with your birth control pill (Lybrel, which contains ethinyl estradiol and levonorgestrel). This plant is moved partly by a protein pump in your gut and liver called P-glycoprotein. In lab dishes, Bulbine appeared to rev up that pump, which could push more of your hormones out before they're absorbed. In theory, that might leave you with slightly lower hormone levels.

Why this matters: with a birth control pill, even small drops in hormone levels can mean less reliable protection or some breakthrough spotting. I want to stress this is only a theoretical, test-tube finding, not proven in people. Still, since pregnancy prevention is at stake, please check with your pharmacist or doctor before pairing them.

References
  1. Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. 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

Bulbine Natalensis Also Interacts With Other Medications

Bulbine Natalensis has 918 moderate known drug interactions in our database — the Ethinyl estradiol, Levonogestrel 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 Bulbine Natalensis

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

Everything else you take

See Every Supplement That Interacts With Ethinyl estradiol, Levonogestrel

This page covers Bulbine Natalensis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl estradiol, Levonogestrel page lists 239 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 · 195 moderate · 38 minor.

From our pharmacist’s overview on the Ethinyl estradiol, Levonogestrel page

“A daily birth control pill like Lybrel (ethinyl estradiol with levonorgestrel) only works when enough hormone stays in the bloodstream, and that is exactly what several supplements on this page can undermine. This list deserves genuine care, starting with the six major-rated entries.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl estradiol, Levonogestrel interaction page

One more smart check

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

We hold 51 real supplement products containing Bulbine Natalensis, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Bulbine Natalensis. Your product may carry other ingredients that interact with Ethinyl estradiol, Levonogestrel too, on top of Bulbine Natalensis — 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 Bulbine Natalensis and Ethinyl estradiol, Levonogestrel 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 Bulbine Natalensis
Top half

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

29 days ago today
Medication Ethinyl estradiol, Levonogestrel
Top 25%

#526 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 Bulbine Natalensis

What is Bulbine Natalensis?

  • Boosting testosterone
  • Improving libido
  • Muscle building and athletic performance
  • General male vitality

Bulbine natalensis is a South African plant marketed mainly as a testosterone-boosting and libido supplement, but the human evidence is essentially absent and most claims come from animal studies. Animal research has also raised concerns about possible liver and kidney harm at higher doses, so caution is warranted. Talk to your pharmacist or doctor before trying it.

Read the full Bulbine Natalensis monograph & all interactions
Keep checking

Other Drugs & Bulbine Natalensis

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

0Major
918Moderate
0Minor
1,911No known interaction
Moderate

918 interactions

Showing 60 of 918 moderate interactions — see all 918 on the Bulbine Natalensis page.

No interaction 1,911 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 Bulbine Natalensis and Ethinyl estradiol, Levonogestrel Together: Common Questions

Can you take Bulbine Natalensis with Ethinyl estradiol, Levonogestrel?
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 Bulbine Natalensis and Ethinyl estradiol, Levonogestrel?
Ethinyl estradiol, Levonogestrel belongs to more than one drug category, and Bulbine Natalensis 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 Bulbine Natalensis and Ethinyl estradiol, Levonogestrel 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.