Drug & supplement interaction

Neem + Siponimod

Siponimod brand name: Mayzent.

Moderate Interaction
The bottom line Moderate

Siponimod falls into 3 drug categories that Neem can interact with; the most serious is rated moderate. Theoretically, neem leaf extract might increase the levels and clinical effects of CYP3A4 substrates.

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

Neem and Siponimod

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

Why Are There 3 Interactions?

Neem interacts with whole categories of medication. Siponimod falls into 3 of those categories, so it can interact with Neem 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

1 of 3

Why this applies to Siponimod

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

Theoretically, neem leaf extract might increase the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that neem leaf methanol extract inhibits CYP3A4 enzymes. So far, this reaction has not been reported 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 basic idea with Siponimod (Mayzent) and neem. Your body partly clears siponimod using a liver enzyme called CYP3A4. In test-tube studies, neem leaf extract seems to slow that same enzyme down. If that happened in a real person, siponimod could build up a bit more than expected, which might mean stronger effects and more side effects like a slower heart rate (especially when you first start), headache, dizziness, higher blood pressure, or swelling.

I want to keep this in perspective, though. This is only lab data, and it has not been seen in actual patients. Still, since siponimod is dosed carefully based on your genetics and heart response, it's worth a quick chat with your neurologist or pharmacist before combining the two.

References
  1. Amaeze O, Eng H, Horlbogen L, Varma MVS, Slitt A. Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria. Eur J Drug Metab Pharmacokinet. 2021;46(3):437-450. PubMed
Moderate

IMMUNOSUPPRESSANTS

2 of 3

Siponimod also falls under IMMUNOSUPPRESSANTS.

Theoretically, neem might decrease the effectiveness of immunosuppressants.
Animal research suggests that neem might have immunostimulant effects.
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 idea worth knowing if you're on Siponimod (Mayzent) for MS. This drug works by quieting down certain immune cells so they cause less nerve damage. The concern with neem is that, at least in animal studies, it seems to do the opposite and rev the immune system up a bit. In theory, that tug-of-war could blunt how well siponimod holds your MS in check.

I want to be honest with you: this is based only on lab and animal research, not real people taking both together, so it's more of a 'keep an eye on it' than a red alert. Still, because keeping your MS controlled matters so much, please run any neem product past your pharmacist or neurologist before starting it.

References
  1. Upadhyay SN, Dhawan S, Garg S, Talwar GP. Immunomodulatory effects of neem (Azadirachta indica) oil. Int J Immunopharmacol 1992;14:1187-93. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 3

Siponimod also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, neem leaf extract might increase the levels and clinical effects of CYP2C9 substrates.
In vitro research shows that neem leaf methanol extract inhibits CYP2C9 enzymes. So far, this reaction has not been reported 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 Mayzent (siponimod). Your body clears this MS medication mainly through a liver enzyme called CYP2C9. In lab dish studies, neem leaf extract seems to slow that enzyme down. If that held true in people, siponimod could build up a bit higher than expected, which might mean more side effects like a slower heart rate, headaches, dizziness, higher blood pressure, or changes in liver enzymes.

The honest part: this is only a theoretical concern from test-tube work, and it has never actually been reported in a real patient. Still, siponimod is a drug doctors dose carefully based on your genetics, so I wouldn't add a neem supplement without first checking with your pharmacist or neurologist.

References
  1. Amaeze O, Eng H, Horlbogen L, Varma MVS, Slitt A. Cytochrome P450 Enzyme Inhibition and Herb-Drug Interaction Potential of Medicinal Plant Extracts Used for Management of Diabetes in Nigeria. Eur J Drug Metab Pharmacokinet. 2021;46(3):437-450. 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

Neem Also Interacts With Other Medications

Neem has 1,012 moderate known drug interactions in our database — the Siponimod 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 Neem

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

Everything else you take

See Every Supplement That Interacts With Siponimod

This page covers Neem only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Siponimod page lists 190 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 · 147 moderate · 40 minor.

From our pharmacist’s overview on the Siponimod page

“Siponimod (Mayzent) treats secondary progressive multiple sclerosis, and because its blood level depends heavily on two liver enzymes, this is a supplement list to respect. Most of these entries can nudge siponimod levels up or down; the three rated major are grapefruit, which raises them, St.”

Reviewed by 2 · Jul 18, 2026

Open the Siponimod interaction page

One more smart check

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

We hold 288 real supplement products containing Neem, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Neem. Your product may carry other ingredients that interact with Siponimod too, on top of Neem — 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 Neem and Siponimod 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 Neem
Top half

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

29 days ago today
Medication Siponimod
Steady interest

#2,354 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 Neem

What is Neem?

Neem
  • Skin conditions
  • Dental and gum health
  • Antimicrobial and antiparasitic
  • Digestive upset
  • Blood sugar support
  • Insect repellent/pesticide

Neem is a tree from India used for centuries in traditional medicine, especially for skin, dental, and antimicrobial purposes. Some small studies are promising for oral health and skin, but high-quality human evidence is limited for most uses. Neem oil and seed extracts can be toxic if swallowed, especially in children, so use with caution and talk to your pharmacist or doctor first.

Read the full Neem monograph & all interactions
Medication

About Siponimod

What Is Siponimod Used For?

Brand name: Mayzent

Mayzent (siponimod) is approved for adults with relapsing forms of multiple sclerosis (MS). This includes three specific types: clinically isolated syndrome (a first episode of MS-like symptoms), relapsing-remitting MS (periods of attacks followed by recovery), and active secondary progressive MS (a phase where the disease gradually worsens but still has active relapses).

It is taken by mouth once daily and is intended as a long-term treatment to reduce relapses and slow disease progression.

See full Siponimod drug information
Keep checking

Other Drugs & Neem

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

0Major
1,012Moderate
0Minor
1,817No known interaction
Moderate

1,012 interactions

Showing 60 of 1,012 moderate interactions — see all 1,012 on the Neem page.

No interaction 1,817 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 Neem and Siponimod Together: Common Questions

Can you take Neem with Siponimod?
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 Neem and Siponimod?
Siponimod belongs to more than one drug category, and Neem 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 Neem and Siponimod 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.