Drug & supplement interaction

Sweet Orange + Modafinil

Modafinil brand names: Provigil, Sparlon, Alertec.

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

Sweet Orange has a moderate interaction with Modafinil. Sweet orange juice seems to modulate P-glycoprotein (P-gp), which might affect the blood levels of P-gp substrates.

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

Sweet Orange and Modafinil

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

Moderate

P-GLYCOPROTEIN SUBSTRATES

Why this applies to Modafinil

Modafinil falls under P-GLYCOPROTEIN SUBSTRATES — the group Sweet Orange interacts with.

Sweet orange juice seems to modulate P-glycoprotein (P-gp), which might affect the blood levels of P-gp substrates.
Animal and in vitro research suggest that orange juice extract inhibits drug efflux by P-gp, increasing absorption and levels of P-gp substrates. In contrast, pharmacokinetic research in humans shows that drinking large amounts of sweet orange juice decreases absorption and levels of the P-gp substrate celiprolol. This suggests that orange juice actually induces drug efflux by P-gp or affects drug levels by another mechanism such as inhibiting the gut drug transporter called organic anion transporting polypeptide (OATP). Until more is known, sweet orange juice should be used cautiously in people taking P-gp substrates.
Severity Moderate Likelihood Possible Evidence B

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: modafinil is moved around your body partly by a transporter called P-glycoprotein (P-gp), and sweet orange juice may nudge that transporter one way or the other. In people, large amounts of orange juice actually seemed to lower the absorption of one P-gp drug, so it's possible that big servings of juice could slightly reduce how much modafinil gets into your system. That might mean a touch less of the wake-promoting effect you count on.

I want to be honest that this is shaky evidence, mostly lab studies and one drug that isn't modafinil, so the real-world impact is uncertain. An occasional orange is unlikely to matter. If you drink large glasses of juice daily, just mention it to your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Bailey DG, Dresser GK, Munoz C, et al. Reduction of fexofenadine bioavailability by fruit juices. Clin Pharmacol Ther 2001;69:P21.
  2. Lilja JJ, Juntti-Patinen L, Neuvonen PJ. Orange juice substantially reduces the bioavailability of the beta-adrenergic-blocking agent celiprolol. Clin Pharmacol Ther 2004;75:184-90.
  3. Tian R, Koyabu N, Takanaga H, et al. Effects of grapefruit juice and orange juice on the intestinal efflux of P-glycoprotein substrates. Pharm Res 2002;19:802-9. PubMed
  4. Takanaga H, Ohnishi A, Yamada S, et al. Polymethoxylated flavones in orange juice are inhibitors of P-glycoprotein but not cytochrome P450 3A4. J Pharmacol Exp Ther 2000;293:230-6. DOI

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

Sweet Orange Also Interacts With Other Medications

Sweet Orange has 48 major, 197 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.

Major 48 Moderate 197 No known interaction 2,585 (incl. Modafinil)
Taking anything else?

Check Another of Your Medications Against Sweet Orange

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

Everything else you take

See Every Supplement That Interacts With Modafinil

This page covers Sweet Orange 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 Sweet Orange as Part of a Dietary Supplement Product? Check It for Interactions

We hold 678 real supplement products containing Sweet Orange, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sweet Orange. Your product may carry other ingredients that interact with Modafinil too, on top of Sweet Orange — 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 Sweet Orange 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 Sweet Orange
Top 25%

#266 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 Sweet Orange

What is Sweet Orange?

Sweet Orange
  • Vitamin C source
  • Digestive upset
  • Stress and relaxation (aromatherapy)
  • Cold and respiratory support
  • Antioxidant support

Sweet orange is a common citrus fruit that is a good source of vitamin C, fiber, and antioxidants, and is enjoyed as a food worldwide. Its peel and essential oil are used in aromatherapy and traditional remedies, but strong scientific proof for most medicinal claims is limited. The fruit and juice are safe for most people as food, while concentrated oils and extracts deserve more caution.

Read the full Sweet Orange 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 & Sweet Orange

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

48Major
197Moderate
0Minor
2,584No known interaction
48 Major 197 Moderate 2,584 No interaction
Major

48 interactions

Moderate

197 interactions

Showing 60 of 197 moderate interactions — see all 197 on the Sweet Orange page.

No interaction 2,584 drugs checked — show the list

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

Showing the 60 most looked-up of 2,584 medications checked with no known interaction — see the full Sweet Orange list.

See the full Sweet Orange 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
Sweet Orange 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 Sweet Orange and Modafinil Together: Common Questions

Can you take Sweet Orange 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 Sweet Orange 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 Sweet Orange?

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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.