Drug & supplement interaction

Grapefruit + Fosphenytoin Sodium

Fosphenytoin Sodium brand name: Sesquient.

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

Fosphenytoin Sodium falls into 3 drug categories that Grapefruit can interact with; the most serious is rated major. Grapefruit or grapefruit juice, especially if consumed in large amounts, can cause additive QT interval prolongation when taken with QT interval-prolonging drugs, potentially increasing the risk of ventricular arrhythmias.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions3
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grapefruit and Fosphenytoin Sodium

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Grapefruit interacts with whole categories of medication. Fosphenytoin Sodium falls into 3 of those categories, so it can interact with Grapefruit in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

QT INTERVAL-PROLONGING DRUGS

1 of 3

Why this applies to Fosphenytoin Sodium

Fosphenytoin Sodium falls under QT INTERVAL-PROLONGING DRUGS — the group Grapefruit interacts with.

Grapefruit or grapefruit juice, especially if consumed in large amounts, can cause additive QT interval prolongation when taken with QT interval-prolonging drugs, potentially increasing the risk of ventricular arrhythmias.
Clinical research in healthy volunteers shows that drinking 6 liters of grapefruit juice over 6 hours prolonged the QTc by a peak amount of 14 milliseconds (ms). This prolongation was similar to the QT prolongation caused by the drug moxifloxacin. In individuals with long QT syndrome, a smaller dose of grapefruit juice, 1.5 liters, resulted in a greater peak QTc prolongation of about 30 ms. The effect of smaller quantities of grapefruit juice on the QT interval is unclear.
Severity Major Likelihood Probable Evidence B

Interaction 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..

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

Here's something a little different from the usual grapefruit story. Most grapefruit warnings are about it blocking a liver enzyme, but with fosphenytoin (Sesquient) the concern on file is about your heart's rhythm. Grapefruit, especially in very large amounts, can stretch out the QT interval (a part of your heartbeat on an ECG). Fosphenytoin can do the same thing, so pairing them may add up and, in rare cases, raise the risk of a dangerous irregular heartbeat.

The good news: the studies that showed this used huge volumes of grapefruit juice (several liters). A normal serving with breakfast is far less likely to matter. Still, since fosphenytoin is usually given in a hospital or urgent setting, this is worth a quick word with your pharmacist or doctor before drinking large amounts.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Chorin E, Hochstadt A, Granot Y, et al. Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome. Heart Rhythm. 2019. pii: S1547-5271(19)30368-6. PubMed
Moderate

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

2 of 3

Fosphenytoin Sodium also falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES.

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C19.
In vitro research suggests that grapefruit juice might inhibit CYP2C19 enzymes. Also, a small clinical study shows that taking grapefruit juice with clopidogrel, an antiplatelet prodrug that is metabolized primarily by CYP2C19, decreases plasma levels of the active metabolite and impairs the antiplatelet effect of clopidogrel. This effect is likely due to grapefruit-induced inhibition of CYP2C19.
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 thing with fosphenytoin: once it's in your body, it converts to phenytoin, your active seizure medicine. One of the liver enzymes that helps clear phenytoin is CYP2C19, and grapefruit can mildly slow that enzyme down. Fosphenytoin is not a prodrug in the sense that matters here, it works by turning into active phenytoin, so blocking the enzyme could let phenytoin levels creep up a bit.

Phenytoin is a narrow-window drug, meaning small changes can tip you into side effects like dizziness, unsteady walking, slurred speech, or drowsiness. That said, this concern is mostly theoretical and based on lab work, not strong human studies. Still, please ask your pharmacist or doctor before making grapefruit a regular habit.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Holmberg MT, Tornio A, Neuvonen M, Neuvonen PJ, Backman JT, Niemi M. Grapefruit juice inhibits the metabolic activation of clopidogrel. Clin Pharmacol Ther. 2014 Mar;95(3):307-13. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

3 of 3

Fosphenytoin Sodium also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C9.
In vitro research suggests that grapefruit juice might inhibit CYP2C9 enzymes. So far, this interaction has not been reported in humans.
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 situation with Sesquient (fosphenytoin). Once it's in your body, fosphenytoin converts into phenytoin, the active seizure medicine, and phenytoin is mostly cleared by a liver enzyme called CYP2C9. The concern on file is that compounds in grapefruit might slow that enzyme down a little. If that happened, phenytoin could build up, and that matters because phenytoin has a narrow safety window. Too much can cause dizziness, unsteady walking, slurred speech, double vision, or drowsiness.

That said, this is theoretical. It comes only from test-tube research and hasn't actually been seen in people. I wouldn't panic, but since this drug is so dose-sensitive, mention your grapefruit habits to your doctor or pharmacist before making it a regular thing.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 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

Grapefruit Also Interacts With Other Medications

Grapefruit has 775 major, 151 moderate, 63 minor known drug interactions in our database — the Fosphenytoin Sodium one above is among them. If you take anything else, check it against the full list below.

Major 775 Moderate 151 Minor 63 No known interaction 1,841 (incl. Fosphenytoin Sodium)
Taking anything else?

Check Another of Your Medications Against Grapefruit

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

From our Q&A

Questions About Grapefruit or Fosphenytoin Sodium

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grapefruit or Fosphenytoin Sodium, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Fosphenytoin Sodium

This page covers Grapefruit only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Fosphenytoin Sodium page lists 212 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), American Hellebore (major), Arsenic (major), Beer (major) and Cesium (major).

By severity: 14 major · 179 moderate · 19 minor.

From our pharmacist’s overview on the Fosphenytoin Sodium page

“Fosphenytoin sodium (Sesquient) converts to phenytoin in the body, and phenytoin is unforgiving about blood levels. A little too low invites seizures, a little too high brings toxicity.”

Reviewed by 2 · Jul 18, 2026

Open the Fosphenytoin Sodium interaction page

One more smart check

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

We hold 1,144 real supplement products containing Grapefruit, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grapefruit. Your product may carry other ingredients that interact with Fosphenytoin Sodium too, on top of Grapefruit — 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 Grapefruit and Fosphenytoin Sodium 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 Grapefruit
Top 10%

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

29 days ago today
Medication Fosphenytoin Sodium
Steady interest

#2,220 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 Grapefruit

What is Grapefruit?

Grapefruit
  • Source of vitamin C
  • Digestive complaints
  • Antimicrobial (seed extract)
  • Weight management
  • Skin and cosmetic uses

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for serious interactions with many prescription medicines, so anyone taking medication should check with a pharmacist or doctor before consuming it regularly.

Read the full Grapefruit monograph & all interactions
Keep checking

Other Drugs & Grapefruit

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

775Major
151Moderate
63Minor
1,840No known interaction
775 Major 151 Moderate 63 Minor 1,840 No interaction
Major

775 interactions

Showing 60 of 775 major interactions — see all 775 on the Grapefruit page.

Moderate

151 interactions

Showing 60 of 151 moderate interactions — see all 151 on the Grapefruit page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Grapefruit page.

No interaction 1,840 drugs checked — show the list

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

Showing the 60 most looked-up of 1,840 medications checked with no known interaction — see the full Grapefruit list.

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

Can you take Grapefruit with Fosphenytoin Sodium?
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 3 interactions listed for Grapefruit and Fosphenytoin Sodium?
Fosphenytoin Sodium belongs to more than one drug category, and Grapefruit 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 Grapefruit and Fosphenytoin Sodium 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 Fosphenytoin Sodium and Grapefruit?

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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.