Drug & supplement interaction

Bulbine Natalensis + Ethinyl Estradiol, Levonorgestrel

Ethinyl Estradiol, Levonorgestrel brand names: Levlite 28, Tri-Levlen 21, Tri-Levlen 28, Levlite, Trivora-28, and others.

Moderate Interaction
The bottom line Moderate

Ethinyl Estradiol, Levonorgestrel 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, Levonorgestrel

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, Levonorgestrel 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, Levonorgestrel

Ethinyl Estradiol, Levonorgestrel 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 short version: your birth control pill (ethinyl estradiol plus levonorgestrel) is partly broken down by a liver enzyme called CYP1A2. Lab studies hint that Bulbine natalensis may slightly speed up that enzyme. In theory, that could clear the hormones out of your body a little faster and lower their levels. For a contraceptive, weaker hormone levels can mean less reliable protection against pregnancy and possibly more breakthrough bleeding or spotting.

I want to be honest about the strength of this, though. This is based only on test-tube and animal data, never confirmed in people, so it's far from proven. Still, because an unplanned pregnancy is a big deal, I'd play it safe and chat with your pharmacist or doctor before combining the two.

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, Levonorgestrel 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

Your birth control pill combines two hormones (ethinyl estradiol and levonorgestrel), and your body clears them partly through a liver enzyme called CYP3A4. In lab and cell studies, Bulbine natalensis appears to speed up that enzyme. If that happened in real life, your body might break down the hormones a little faster, which could lower their levels and, in theory, make the pill less reliable at preventing pregnancy. You might also notice more breakthrough bleeding or spotting.

I want to be straight with you, though: this is only a theoretical concern from test-tube and animal data, not from people, so we really don't know how much it matters. Since an unplanned pregnancy is a big deal, please run this by your pharmacist or doctor before combining the two.

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, Levonorgestrel 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 situation if you take Bulbine natalensis alongside your birth control pill (Levlite, Trivora, Triphasil and similar combos of ethinyl estradiol and levonorgestrel). Your pill partly relies on a transporter protein called p-glycoprotein to move it in and out of cells. Lab studies suggest Bulbine may rev up that transporter, which in theory could shuttle some of the hormones out faster and lower their levels in your body.

Why that matters: weaker hormone levels can mean less reliable pregnancy protection, plus possible breakthrough spotting or bleeding. I want to stress this is only test-tube data, not proven in people, so it's a theoretical concern. Still, since reliable contraception is at stake, please check with your pharmacist or doctor before combining the two.

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, Levonorgestrel 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, Levonorgestrel

This page covers Bulbine Natalensis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Levonorgestrel 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.

Open the Ethinyl Estradiol, Levonorgestrel 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, Levonorgestrel 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, Levonorgestrel 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
Steady interest

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

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

#407 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, Levonorgestrel Together: Common Questions

Can you take Bulbine Natalensis with Ethinyl Estradiol, Levonorgestrel?
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, Levonorgestrel?
Ethinyl Estradiol, Levonorgestrel 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, Levonorgestrel 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.