Drug & supplement interaction

Schisandra + Sirolimus

Sirolimus brand name: Rapamune.

Moderate Interaction
The bottom line Moderate

Sirolimus falls into 3 drug categories that Schisandra can interact with; the most serious is rated moderate. Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.

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

Schisandra and Sirolimus

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

Why Are There 3 Interactions?

Schisandra interacts with whole categories of medication. Sirolimus falls into 3 of those categories, so it can interact with Schisandra 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 3A4 (CYP3A4) SUBSTRATES

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Why this applies to Sirolimus

Sirolimus falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Schisandra interacts with.

Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.
Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol. Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism, this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.
Severity Moderate Likelihood Probable Evidence D

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 key thing with sirolimus (Rapamune): your body relies on a liver enzyme called CYP3A4 to break it down and keep blood levels in a safe range. Schisandra appears to slow that enzyme, so the worry is that sirolimus could build up higher than expected. Since sirolimus is a drug we dose very carefully (it's a narrow-margin medication that's monitored with blood tests), even a modest bump matters.

Higher levels could mean more side effects like mouth sores, high cholesterol or triglycerides, swelling, low blood counts, or kidney trouble. Most of this evidence is from lab and animal work plus related drugs, not sirolimus directly, so it's a reasonable caution rather than a sure thing. Please don't change anything on your own. Check with your transplant team or pharmacist before adding schisandra.

References
  1. Iwata H, Tezuka Y, Kadota S, et al. Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos 2004;32:1351-8. PubMed
  2. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  3. Qin XL, Bi HC, Wang XD, et al. Mechanistic understanding of the different effects of Wuhzi Tablet (Schisandra sphenanthera extract) on the absorption and first-pass intestinal and hepatic metabolism of tacrolimus (FK506). Int J Pharm 2010;389:114-21.
  4. Makino, T., Mizuno, F., and Mizukami, H. Does a kampo medicine containing schisandra fruit affect pharmacokinetics of nifedipine like grapefruit juice? Biol.Pharm.Bull. 2006;29(10):2065-2069. PubMed
  5. Fan L, Mao XQ, Tao GY, Wang G, Jiang F, Chen Y, Li Q, Zhang W, Lei HP, Hu DL, Huang YF, Wang D, Zhou HH. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica. 2009 Mar;39(
  6. Jiang W, Wang X, Xu X, Kong L. Effect of Schisandra sphenanthera extract on the concentration of tacrolimus in the blood of liver transplant patients. Int J Clin Pharmacol Ther. 2010 Mar;48(3):224-9. PubMed
  7. Xin HW, Wu XC, Li Q, Yu AR, Xiong L. Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers. Br J Clin Pharmacol. 2009 May;67(5):541-6.
  8. Li J, Chen S, Qin X, et at. Wuzhi Tablet (<i>Schisandra sphenanthera</i> Extract) is a Promising Tacrolimus-Sparing Agent for Renal Transplant Recipients Who are CYP3A5 Expressers: a Two-Phase Prospective Study. Drug Metab Dispos. 2017;45(11):1114-1119.
  9. Qin XL, Li JL, Wang SH, Chen X, Huang M, Bi HC. Co-administration of Wuzhi tablet (Schisandra sphenanthera extract) alters tacrolimus pharmacokinetics in a dose- and time-dependent manner in rats. J Ethnopharmacol. 2020;263:113233. PubMed
  10. Chen L, Ji N, Zhang M, Chen W. The influence of Wuzhi capsule on the pharmacokinetics of cyclophosphamide. Recent Pat Anticancer Drug Discov 2021. PubMed
  11. Cheng F, Li Q, Wang J, Zeng F, Zhang Y. Effects and safety evaluation of Wuzhi capsules combined with tacrolimus for the treatment of kidney transplantation recipients. J Clin Pharm Ther 2021;46(6):1636-49. PubMed
  12. Teng F, Wang W, Zhang W, et al. Effect of hepar-protecting Wuzhi capsule on pharmacokinetics and dose-effect character of tacrolimus in healthy volunteers. Biopharm Drug Dispos 2022.
  13. Kou K, Sun X, Li M, et al. Beneficial effects of Wuzhi capsule on tacrolimus blood concentrations in liver transplant patients with different donor-recipient CYP3A5 genotypes. J Clin Pharm Ther 2022;47(2):200-10. PubMed
  14. Peng Y, Jiang F, Zhou R, et al. Clinical evaluation of the efficacy and safety of co-administration of Wuzhi capsule and tacrolimus in adult Chinese patients with myasthenia gravis. Neuropsychiatr Dis Treat 2021;17:2281-9. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

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Sirolimus also falls under P-GLYCOPROTEIN SUBSTRATES.

Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.
In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines. Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate. Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.
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 body uses a pump called P-glycoprotein to push some of the sirolimus back out of your gut and limit how much gets in. Schisandra appears to slow that pump down. So pairing the two could let more sirolimus into your bloodstream than usual, raising its levels and effects.

Sirolimus is a fussy drug where small changes matter, and higher levels can mean more side effects like mouth sores, swelling, high cholesterol, low blood counts, or too much immune suppression. Now, this concern mostly comes from lab and animal research plus one study on a different drug, so it is not proven for sirolimus. Still, since your transplant team already tracks your sirolimus blood levels closely, please check with them or your pharmacist before adding schisandra.

References
  1. Qin XL, Bi HC, Wang XD, et al. Mechanistic understanding of the different effects of Wuhzi Tablet (Schisandra sphenanthera extract) on the absorption and first-pass intestinal and hepatic metabolism of tacrolimus (FK506). Int J Pharm 2010;389:114-21.
  2. Fan L, Mao XQ, Tao GY, Wang G, Jiang F, Chen Y, Li Q, Zhang W, Lei HP, Hu DL, Huang YF, Wang D, Zhou HH. Effect of Schisandra chinensis extract and Ginkgo biloba extract on the pharmacokinetics of talinolol in healthy volunteers. Xenobiotica. 2009 Mar;39(
  3. Yoo HH, Lee M, Lee MW, Lim SY, Shin J, Kim DH. Effects of Schisandra lignans on P-glycoprotein-mediated drug efflux in human intestinal Caco-2. Planta Med. 2007;73(5):444-50.
  4. Qiangrong P, Wang T, Lu Q, Hu X. Schisandrin B--a novel inhibitor of P-glycoprotein. Biochem Biophys Res Commun. 2005;335(2):406-11. PubMed
Moderate

SIROLIMUS (Rapamune)

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Schisandra can increase the levels and clinical effects of sirolimus.
A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter.
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 gist for you: Schisandra can push your sirolimus levels up. In one small study in healthy people, taking schisandra for about two weeks roughly doubled the amount of sirolimus in the bloodstream. That happens because schisandra appears to slow down CYP3A4 (and possibly a transporter called P-glycoprotein), which are the main ways your body clears this drug. Sirolimus is active as-is, not a prodrug, so blocking that cleanup means more drug hangs around.

Sirolimus has a narrow safety window, so even a modest jump matters. Higher levels can mean more side effects like mouth sores, swelling, high cholesterol, low blood counts, or kidney strain. Please don't change anything on your own. Talk with your transplant team or pharmacist before adding schisandra, since they monitor your blood levels closely.

References
  1. Yoo HH, Lee M, Lee MW, Lim SY, Shin J, Kim DH. Effects of Schisandra lignans on P-glycoprotein-mediated drug efflux in human intestinal Caco-2. Planta Med. 2007;73(5):444-50.

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

Schisandra Also Interacts With Other Medications

Schisandra has 802 moderate known drug interactions in our database — the Sirolimus 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 Schisandra

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

From our Q&A

Questions About Schisandra or Sirolimus

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Schisandra or Sirolimus, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Sirolimus

This page covers Schisandra only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sirolimus page lists 188 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 Active Hexose Correlated Compound (ahcc) (moderate).

By severity: 3 major · 149 moderate · 36 minor.

From our pharmacist’s overview on the Sirolimus page

“Sirolimus (Rapamune) is the anti-rejection medicine transplant patients depend on, and it is a narrow-therapeutic-index drug, meaning small shifts in its blood level can invite rejection on one side or toxicity on the other. That is why the 188 supplements on this page deserve genuine wariness, starting with the three rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Sirolimus interaction page

One more smart check

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

We hold 2,577 real supplement products containing Schisandra, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Schisandra. Your product may carry other ingredients that interact with Sirolimus too, on top of Schisandra — 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 Schisandra and Sirolimus 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 Schisandra
Top 10%

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

29 days ago today
Medication Sirolimus
Steady interest

#2,237 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 Schisandra

What is Schisandra?

Schisandra
  • Fatigue and low energy
  • Stress and adaptogen support
  • Liver health
  • Mental focus and performance
  • Menopause symptoms
  • Respiratory complaints

Schisandra is a traditional Chinese medicine berry used as an adaptogen for stress, fatigue, and liver support. Human evidence is limited and most claims are not well proven, but it appears reasonably well tolerated by most healthy adults when used short term. Pregnant and breastfeeding people should avoid it, and anyone with a health condition should check with a pharmacist or doctor first.

Read the full Schisandra monograph & all interactions
Medication

About Sirolimus

What Is Sirolimus Used For?

Brand name: Rapamune

Sirolimus oral solution and tablets are used to help prevent organ rejection in kidney (renal) transplant patients aged 13 and older. They are also used to treat lymphangioleiomyomatosis (LAM) — a rare lung disease in which abnormal muscle-like cells invade lung tissue.

Fyarro (sirolimus, intravenous injection) is used to treat adults with locally advanced, unresectable, or metastatic malignant PEComa — a rare tumor that grows in soft tissue or organs. Hyftor (sirolimus topical gel) is used to treat facial angiofibroma (small benign skin growths on the face) associated with tuberous sclerosis in adults and children aged 6 and older.

See full Sirolimus drug information
Keep checking

Other Drugs & Schisandra

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

0Major
802Moderate
0Minor
2,027No known interaction
Moderate

802 interactions

Showing 60 of 802 moderate interactions — see all 802 on the Schisandra page.

No interaction 2,027 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 Schisandra and Sirolimus Together: Common Questions

Can you take Schisandra with Sirolimus?
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 Schisandra and Sirolimus?
Sirolimus belongs to more than one drug category, and Schisandra 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 Schisandra and Sirolimus 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.