Drug & supplement interaction

Gravel Root + Modafinil

Modafinil brand names: Provigil, Sparlon, Alertec.

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

Gravel Root has a moderate interaction with Modafinil. Hepatotoxic pyrrolizidine alkaloids (PA) are substrates of cytochrome P450 3A4 (CYP3A4).

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

Gravel Root and Modafinil

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS

Why this applies to Modafinil

Modafinil falls under CYTOCHROME P450 3A4 (CYP3A4) INDUCERS — the group Gravel Root interacts with.

Hepatotoxic pyrrolizidine alkaloids (PA) are substrates of cytochrome P450 3A4 (CYP3A4). Theoretically, drugs that induce CYP3A4 might increase the conversion of PAs to toxic metabolites. Some drugs that induce CYP3A4 include carbamazepine (Tegretol), phenobarbital, phenytoin (Dilantin), rifampin, rifabutin (Mycobutin), and others.
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 key thing to understand with this pairing. Gravel Root may contain pyrrolizidine alkaloids, which are plant compounds that can be hard on the liver. Your body uses an enzyme called CYP3A4 to process them, and unfortunately that processing can turn them into more toxic byproducts. Modafinil is a known booster of that same CYP3A4 enzyme, so in theory it could speed up the formation of those liver-stressing metabolites from the herb.

I want to be honest about the evidence here: this concern comes from lab and animal data, not real human studies, so it's more of a caution than a proven danger. Still, because Gravel Root's liver safety is poorly studied to begin with, I'd lean toward avoiding it while on Modafinil. Please run it past your pharmacist or doctor before combining them.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chojkier M. Hepatic sinusoidal-obstruction syndrome: toxicity of pyrrolizidine alkaloids. J Hepatol 2003;39:437-46. PubMed
  2. Wang YP, Yan J, Fu PP, Chou MW. Human liver microsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent alkaloid. Toxicol Lett 2005;155:411-20. 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

Gravel Root Also Interacts With Other Medications

Gravel Root has 87 moderate known drug interactions in our database — the Modafinil one above is one of them. If you take anything else, check it against the full list below.

Moderate 87 No known interaction 2,743 (incl. Modafinil)
Taking anything else?

Check Another of Your Medications Against Gravel Root

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

Everything else you take

See Every Supplement That Interacts With Modafinil

This page covers Gravel Root only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Modafinil page lists 197 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Adrafinil (major), Ephedra (major), Grapefruit (major) and Peyote (major).

By severity: 8 major · 150 moderate · 39 minor.

From our pharmacist’s overview on the Modafinil page

“Of the 197 supplements and herbs flagged for modafinil (Provigil, Alertec), eight carry a major rating, and those deserve real caution. Most of the rest fall into two themes.”

Reviewed by 2 · Jul 18, 2026

Open the Modafinil interaction page

One more smart check

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

We hold 20 real supplement products containing Gravel Root, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Gravel Root. Your product may carry other ingredients that interact with Modafinil too, on top of Gravel Root — 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 Gravel Root and Modafinil 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 Gravel Root
Steady interest

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

29 days ago today
Medication Modafinil
Top half

#1,312 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 Gravel Root

What is Gravel Root?

  • Kidney stones
  • Urinary tract complaints
  • Fluid retention
  • Gout and joint pain
  • Bladder irritation

Gravel Root is a traditional North American herb long used by herbalists for kidney stones and urinary problems, but there is very little modern scientific evidence to support these uses. Because it contains compounds that may harm the liver and its safety is poorly studied, it should be used with caution, if at all, and avoided in pregnancy and breastfeeding.

Read the full Gravel Root monograph & all interactions
Medication

About Modafinil

What Is Modafinil Used For?

Brand names: Provigil, Sparlon, Alertec

Modafinil (also sold as Provigil) is used to improve wakefulness in adults who experience excessive sleepiness due to narcolepsy, obstructive sleep apnea (OSA), or shift work disorder (SWD).

In OSA, modafinil treats the sleepiness — not the underlying airway obstruction itself. It is used alongside standard treatments such as CPAP (a breathing device worn during sleep), not as a replacement for them. If CPAP is appropriate for you, your doctor will want you to use it consistently even while taking modafinil.

See full Modafinil drug information
Keep checking

Other Drugs & Gravel Root

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

0Major
87Moderate
0Minor
2,742No known interaction
87 Moderate 2,742 No interaction
Moderate

87 interactions

Showing 60 of 87 moderate interactions — see all 87 on the Gravel Root page.

No interaction 2,742 drugs checked — show the list

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

Showing the 60 most looked-up of 2,742 medications checked with no known interaction — see the full Gravel Root list.

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

Can you take Gravel Root with Modafinil?
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.
How serious is the Gravel Root and Modafinil 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 Modafinil and Gravel Root?

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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.