Drug & supplement interaction

Syrian Rue + Macitentan

Macitentan brand name: Opsumit.

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

Macitentan falls into 2 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with hepatotoxic drugs.

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

Syrian Rue and Macitentan

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

Why Are There 2 Interactions?

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

Moderate

HEPATOTOXIC DRUGS

1 of 2

Why this applies to Macitentan

Macitentan falls under HEPATOTOXIC DRUGS — the group Syrian Rue interacts with.

Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with hepatotoxic drugs.
Cases of hepatotoxicity and hepatic failure have been reported in patients who ingested a large quantity (up to 100 grams) of Syrian rue seeds.
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 Syrian Rue and Macitentan (Opsumit). This isn't really an enzyme tug-of-war that changes your drug levels. Instead, both can be tough on the liver. Macitentan already carries a small risk of raising liver enzymes, which is why your doctor checks bloodwork. Syrian Rue, especially in large amounts, has been linked to liver injury and even liver failure in reported cases. Stack the two and you may be adding extra strain on the same organ.

To be honest, this is a theoretical worry based on how these things behave, and the scary cases involved eating huge quantities of seeds. Still, I wouldn't combine them without checking with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yuruktumen, A., Karaduman, S., Bengi, F., and Fowler, J. Syrian rue tea: a recipe for disaster. Clin Toxicol (Phila) 2008;46(8):749-752. PubMed
  2. Berdai MA, Labib S, Harandou M. Peganum harmala L. Intoxication in a Pregnant Woman. Case Rep Emerg Med 2014;2014:783236.
  3. Ghizlane EA, Manal M, Ines HA, et al. Fatal poisoning of pregnant women by peganum harmala L.: a case reports. Ann Med Surg (Lond) 2021;68:102649. PubMed
  4. Durmaz Çelik N, Ger Akarsu F, Ozkan S, Özdemir AÖ, Aykac Ö, Memmedova F. Herbal teas can be harmful: a case of Peganum harmala induced coma in a patient with Parkinson's disease. Neurocase 2021;27(2):117-119.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Macitentan also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP3A4.
Syrian rue contains beta-carboline alkaloids, including harmine, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids competitively inhibit CYP3A4 enzymes.
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 Opsumit (macitentan): your liver uses an enzyme called CYP3A4 to help clear this drug from your body. Lab studies suggest the harmala alkaloids in Syrian Rue can slow that same enzyme down. If that happens, macitentan could build up more than expected, which might lead to stronger side effects like swelling in your legs and ankles, headaches, low blood pressure, a stuffy nose, or feeling unusually tired.

I want to be honest with you, though. This concern is theoretical and comes from test-tube research, not real patients, so we can't say how big a deal it would be in everyday life. Since Syrian Rue carries its own toxicity risks, please check with your pharmacist or doctor before combining the two.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.

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

Syrian Rue Also Interacts With Other Medications

Syrian Rue has 1,123 moderate known drug interactions in our database — the Macitentan one above is among them. If you take anything else, check it against the full list below.

Moderate 1,123 No known interaction 1,707 (incl. Macitentan)
Taking anything else?

Check Another of Your Medications Against Syrian Rue

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

Everything else you take

See Every Supplement That Interacts With Macitentan

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Macitentan page lists 253 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), American Mistletoe (major), Beer (major) and Grapefruit (major).

By severity: 9 major · 205 moderate · 39 minor.

From our pharmacist’s overview on the Macitentan page

“If you take macitentan (Opsumit) for pulmonary arterial hypertension, study this page rather than skim it. It lists 253 supplement and herbal ingredients, nine rated major.”

Reviewed by 2 · Jul 18, 2026

Open the Macitentan interaction page

How much people look this up

Where Syrian Rue and Macitentan 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 Syrian Rue
Steady interest

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

29 days ago today
Medication Macitentan
Top 25%

#507 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 Syrian Rue

What is Syrian Rue?

  • Traditional remedy for digestive complaints
  • Used as a sedative or for mood
  • Antimicrobial and antiparasitic folk use
  • Used as a dye and incense
  • Recreational psychoactive use

Syrian Rue (Peganum harmala) is a traditional plant whose seeds contain potent compounds called harmala alkaloids, including MAO-inhibiting harmine and harmaline. There is little reliable human evidence that it safely treats any condition, and it carries real risks of toxicity, so it is not recommended for self-treatment. Talk to a pharmacist or doctor before considering it.

Read the full Syrian Rue monograph & all interactions
Medication

About Macitentan

What Is Macitentan Used For?

Brand name: Opsumit

Macitentan tablets — sold under the brand name Opsumit — are used to treat pulmonary arterial hypertension (PAH, WHO Group I), a type of high blood pressure in the arteries of the lungs. The goal is to slow the disease from getting worse and to lower the chance of being hospitalized because of PAH.

In the key clinical study, macitentan was used in adults with mainly moderate-to-severe PAH symptoms. Patients had PAH caused by unknown or inherited causes, connective tissue disorders, or congenital heart disease with repaired shunts.

See full Macitentan drug information
Keep checking

Other Drugs & Syrian Rue

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

0Major
1,123Moderate
0Minor
1,706No known interaction
1,123 Moderate 1,706 No interaction
Moderate

1,123 interactions

Showing 60 of 1,123 moderate interactions — see all 1,123 on the Syrian Rue page.

No interaction 1,706 drugs checked — show the list

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

Showing the 60 most looked-up of 1,706 medications checked with no known interaction — see the full Syrian Rue list.

See the full Syrian Rue interactions page
See every supplement checked against Macitentan, 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
Syrian Rue monograph › Uses, safety, and every drug interaction in one place Macitentan supplement interactions › Every supplement checked against Macitentan, ranked by severity Macitentan 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 Syrian Rue and Macitentan Together: Common Questions

Can you take Syrian Rue with Macitentan?
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 Syrian Rue and Macitentan?
Macitentan belongs to more than one drug category, and Syrian Rue 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 Syrian Rue and Macitentan 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 Macitentan and Syrian Rue?

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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.