Drug & supplement interaction

Bulbine Natalensis + Tolvaptan

Tolvaptan brand names: Samsca, Jynarque.

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

Tolvaptan falls into 2 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 CYP3A4 substrates.

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

Bulbine Natalensis and Tolvaptan

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

Why Are There 2 Interactions?

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

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Tolvaptan

Tolvaptan falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Bulbine Natalensis interacts with.

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 gist for tolvaptan (Samsca or Jynarque). Your body clears this drug using a liver enzyme called CYP3A4. Lab and test-tube studies suggest Bulbine natalensis may speed up that enzyme, which in theory could clear tolvaptan faster and make it less effective. For someone using Jynarque to protect kidney function in polycystic kidney disease, that could mean less benefit over time.

I want to be honest though: this is only a theory from lab data, not something tested in people, so we don't really know how it plays out. On top of that, Bulbine has its own liver and kidney concerns in animal studies, and tolvaptan already needs liver monitoring. Please check with your doctor or pharmacist before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
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

2 of 2

Tolvaptan 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 gist for tolvaptan (Samsca or Jynarque). Your body uses a tiny pump called P-glycoprotein to help move tolvaptan out of cells, and lab studies hint that Bulbine natalensis may rev up that pump. If that actually happened in people, it could push tolvaptan out faster and weaken its effect, so you might notice less of the strong water-shedding action it's known for, or it may not protect your kidneys as well over time.

I want to be honest though: this is only a theoretical concern from test-tube work, not from real patients, and the database itself notes the actual pump activity wasn't even measured. Bulbine also carries its own liver and kidney safety questions, which matters a lot when you're on a kidney medicine. Please loop in your doctor or pharmacist before mixing the two.

Contact Dr. Brian directly if you have additional questions on this interaction
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 Tolvaptan one above is among them. If you take anything else, check it against the full list below.

Moderate 918 No known interaction 1,912 (incl. Tolvaptan)
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 Tolvaptan

This page covers Bulbine Natalensis only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Tolvaptan page lists 145 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), St. John's Wort (major), Acacia Rigidula (moderate) and Adrafinil (moderate).

By severity: 3 major · 104 moderate · 38 minor.

From our pharmacist’s overview on the Tolvaptan page

“People taking tolvaptan (Samsca, Jynarque) for polycystic kidney disease or low blood sodium are on a drug whose blood level depends heavily on one liver enzyme, CYP3A4, and that is exactly where most of these 145 supplements interfere. Grapefruit can drive tolvaptan levels up, St.”

Reviewed by 2 · Jul 18, 2026

Open the Tolvaptan 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 Tolvaptan 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 Tolvaptan 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

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

29 days ago today
Medication Tolvaptan
Steady interest

#2,460 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
Medication

About Tolvaptan (kidney disease)

What Is Tolvaptan (kidney disease) Used For?

Brand names: Samsca, Jynarque

Tolvaptan (brand name Jynarque) is used to slow the decline of kidney function in adults who have autosomal dominant polycystic kidney disease (ADPKD) — a genetic condition where fluid-filled cysts grow in the kidneys over time, gradually damaging them. It is specifically for people whose disease is at risk of progressing quickly.

It does not cure ADPKD, but it works to slow down how fast the kidneys deteriorate, helping preserve kidney function for longer.

See full Tolvaptan (kidney disease) drug information
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
918 Moderate 1,911 No 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

We also checked Bulbine Natalensis against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,911 medications checked with no known interaction — see the full Bulbine Natalensis list.

See the full Bulbine Natalensis interactions page
See every supplement checked against Tolvaptan, 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
Bulbine Natalensis monograph › Uses, safety, and every drug interaction in one place Tolvaptan supplement interactions › Every supplement checked against Tolvaptan, ranked by severity Tolvaptan (kidney disease) drug information › The full plain-English guide to this medication 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 Bulbine Natalensis and Tolvaptan Together: Common Questions

Can you take Bulbine Natalensis with Tolvaptan?
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 2 interactions listed for Bulbine Natalensis and Tolvaptan?
Tolvaptan 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 Tolvaptan 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

Still Have a Question About Tolvaptan and Bulbine Natalensis?

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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.