Drug & supplement interaction

Sweet Orange + Etoposide

Etoposide brand names: VePesid, VP16, Etopophos.

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

Etoposide falls into 2 drug categories that Sweet Orange can interact with; the most serious is rated major. Consuming sweet orange juice can decrease oral absorption of OATP substrates.

Read the full interaction report
SeverityMajor
LikelihoodLikely
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sweet Orange and Etoposide

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

Why Are There 2 Interactions?

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

Major

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

1 of 2

Why this applies to Etoposide

Etoposide falls under ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP) — the group Sweet Orange interacts with.

Consuming sweet orange juice can decrease oral absorption of OATP substrates. Separate administration by at least 4 hours.
Clinical research shows that consuming sweet orange juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP. For example, sweet orange juice decreases bioavailability of fexofenadine, a substrate of OATP, by about 72% and of celiprolol, another OATP substrate, by up to 90%. Since sweet orange juice seems to affect OATP for a short time, recommend separating drug administration and consumption of sweet orange juice by at least 4 hours.
Severity Major Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for etoposide: your body relies on little transporter proteins called OATP to help pull certain medicines from your gut into your bloodstream. Sweet orange juice can temporarily block these transporters, and that can mean less of the drug actually gets absorbed when taken by mouth. We've seen this play out with other OATP medicines, where orange juice cut absorption dramatically.

For a cancer treatment like etoposide, getting less than the intended dose into your system could mean it doesn't work as well against the cancer, which is the real concern here. This isn't about new side effects, it's about reduced effect. The good news is the blocking is short-lived, so spacing the juice and the medicine by at least 4 hours helps. Please confirm the timing with your oncology team or pharmacist 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. Greenblatt DJ. Analysis of drug interactions involving fruit beverages and organic anion-transporting polypeptides. J Clin Pharmacol 2009;49:1403-7. PubMed
  4. Bailey DG. Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol 2010;70:645-55. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 2

Etoposide also falls under P-GLYCOPROTEIN SUBSTRATES.

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 short version on mixing sweet orange with etoposide. Etoposide leans on a gut transporter called P-glycoprotein to control how much of the drug gets absorbed into your bloodstream. Sweet orange juice appears to nudge this transporter, but honestly the human data point in different directions, so we can't say for sure whether your etoposide levels would go up or down.

If levels shifted higher, you might see more of etoposide's usual side effects (low blood counts, mouth sores, nausea, fatigue). If they dropped, the chemo might not work as well. Since this is cancer treatment with a lot riding on it, I wouldn't change anything on your own. Please loop in your oncologist or pharmacist before adding orange juice or citrus supplements.

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 47 major, 198 moderate known drug interactions in our database — the Etoposide one above is among them. If you take anything else, check it against the full list below.

Major 47 Moderate 198 No known interaction 2,585 (incl. Etoposide)
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 Etoposide

This page covers Sweet Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Etoposide page lists 152 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Grapefruit (major), St. John's Wort (major) and Acacia Rigidula (moderate).

By severity: 5 major · 107 moderate · 40 minor.

From our pharmacist’s overview on the Etoposide page

“Chemotherapy is unforgiving of level swings, and swings are exactly what most of this list can cause for etoposide (VePesid, Etopophos). Of the 152 supplements and herbs on file, 121 can change how your liver clears etoposide through the CYP3A4 enzyme, meaning too little drug and an undertreated cancer, or too much and harsher toxicity.”

Reviewed by 2 · Jul 18, 2026

Open the Etoposide 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 Etoposide 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 Etoposide 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 Etoposide
Top half

#1,211 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 Etoposide

What Is Etoposide Used For?

Brand names: VePesid, VP16, Etopophos

Etoposide injection (available as Avopef, Etopophos, Toposar, and Etoposide) is used to treat refractory testicular tumors — cancers that have already been treated with surgery, radiation, and other chemotherapy — always in combination with other cancer drugs. It is also used for small cell lung cancer (SCLC) as a first-line treatment, given together with other chemotherapy and, in the case of Avopef, with immunotherapy as well.

Etoposide capsules (VePesid and Etoposide capsules) are approved for small cell lung cancer as first-line treatment in combination with other chemotherapy agents. Capsule forms are not approved for testicular cancer, as the label notes that adequate data on their use in that setting are not available.

See full Etoposide 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.

47Major
198Moderate
0Minor
2,584No known interaction
47 Major 198 Moderate 2,584 No interaction
Major

47 interactions

Moderate

198 interactions

Showing 60 of 198 moderate interactions — see all 198 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 Etoposide, 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 Etoposide supplement interactions › Every supplement checked against Etoposide, ranked by severity Etoposide 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 Etoposide Together: Common Questions

Can you take Sweet Orange with Etoposide?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Sweet Orange and Etoposide?
Etoposide belongs to more than one drug category, and Sweet Orange 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 Sweet Orange and Etoposide interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Etoposide 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.