Drug & supplement interaction

Sweet Orange + Nalidixic Acid

Nalidixic Acid brand name: NegGram.

Major Interaction
The bottom line Major

Nalidixic Acid 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 Nalidixic Acid

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. Nalidixic Acid 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 Nalidixic Acid

Nalidixic Acid 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 practical takeaway: drinking orange juice around the time you take nalidixic acid can actually block some of it from being absorbed into your body. Orange juice temporarily slows down a gut transporter called OATP, and nalidixic acid relies on that transporter to get from your intestines into your bloodstream. The result is that less of the antibiotic gets in, so it may not work as well at clearing your urinary tract infection.

The good news is the effect is short-lived, so timing is the easy fix. Spacing your orange juice and your dose by at least 4 hours should keep the antibiotic working as intended. Before you change anything, it's worth a quick chat with your pharmacist or doctor to confirm the best schedule for you.

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

QUINOLONE ANTIBIOTICS

2 of 2

Nalidixic Acid also falls under QUINOLONE ANTIBIOTICS.

Calcium-fortified sweet orange juice might reduce quinolone absorption.
Calcium binds to quinolones in the gut. Theoretically, the calcium in certain fortified orange juices can also bind to quinolone antibiotics and reduce their absorption and levels.
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 thing to watch for with nalidixic acid: it's not the orange itself, it's the calcium added to many fortified orange juices. Calcium can grab onto quinolone antibiotics like this one right in your gut and form clumps your body can't absorb well. That means less of the antibiotic actually gets into your bloodstream, which could leave your urinary tract infection undertreated.

The good news is this is a theoretical concern based on how the drug works, not strong proof. Plain orange juice or eating an orange likely isn't a big deal, but calcium-fortified juice is the part to space apart. A simple fix is to separate them by a couple of hours. Check with your pharmacist on the best timing for you.

References
  1. Murry JJ, Healy MD. Drug-mineral interactions: a new responsibility for the hospital dietician. J Am Diet Assoc 1991;91:66-73.
  2. Pletz MW, Petzold P, Allen A, et al. Effect of calcium carbonate on bioavailability of orally administered gemifloxacin. Antimicrob Agents Chemother 2003;47:2158-60.. PubMed
  3. Huang SM, Lesko LJ. Drug-drug, drug-dietary supplement, and drug-citrus fruit and other food interactions: what have we learned? J Clin Pharmacol 2004;44:559-69. PubMed
  4. Kays MB, Overholser BR, Mueller BA, et al. Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin. Am J Kidney Dis. 2003;42(6):1253-9. PubMed
  5. Neuhofel, A. L., Wilton, J. H., Victory, J. M., Hejmanowsk, L. G., and Amsden, G. W. Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction. J Clin Pharmacol. 2002;42(4):461-466. 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 Nalidixic Acid 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 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 Nalidixic Acid

This page covers Sweet Orange only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Nalidixic Acid page lists 146 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Asarabacca (major), Beer (major) and Grapefruit (major).

By severity: 8 major · 118 moderate · 20 minor.

Open the Nalidixic Acid 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 Nalidixic Acid 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 Nalidixic Acid 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 Nalidixic Acid
Top half

#1,166 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
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
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
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 Sweet Orange and Nalidixic Acid Together: Common Questions

Can you take Sweet Orange with Nalidixic Acid?
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 Nalidixic Acid?
Nalidixic Acid 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 Nalidixic Acid 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

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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.