Drug & supplement interaction

Black Seed + Phenytoin

Phenytoin brand names: Dilantin Kapseals, Dilantin, Di-Phen, Dilantin Infatabs, Phenytek, and others.

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

Phenytoin falls into 3 drug categories that Black Seed can interact with; the most serious is rated moderate. Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Seed and Phenytoin

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

Why Are There 3 Interactions?

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

Moderate

CNS DEPRESSANTS

1 of 3

Why this applies to Phenytoin

Phenytoin falls under CNS DEPRESSANTS — the group Black Seed interacts with.

Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.
Animal research suggests that black seed may have CNS depressant effects.
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 simple version: black seed may have a mild calming or sedating effect on the brain, at least in animal studies. Phenytoin (Dilantin) can already make some people feel drowsy, dizzy, or unsteady on their feet. Put the two together and those effects could, in theory, add up and leave you feeling more tired or off-balance than usual.

I want to be honest about the evidence here. This concern comes from lab and animal research, not real-world cases in people, so it's more of a theoretical caution than a proven problem. Small amounts of black seed used as a kitchen spice are very unlikely to matter. Concentrated supplement doses are the bigger question mark. Since phenytoin levels need careful balancing, please check with your pharmacist or doctor before adding a black seed supplement.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Al Naggar, T. B., Gomez-Serranillos, M. P., Carretero, M. E., and Villar, A. M. Neuropharmacological activity of Nigella sativa L. extracts. J Ethnopharmacol. 2003;88(1):63-68. PubMed
Moderate

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

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

Theoretically, black seed might increase levels of drugs metabolized by CYP2C9.
In vitro research suggests that thymoquinone, a constituent of black seed, can decrease the metabolism of phenytoin by a mechanism possibly related to the inhibition of CYP2C9. The effect of black seed on CYP2C9 is unclear. This has not been shown 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 gist: phenytoin is cleared from your body mainly by a liver enzyme called CYP2C9. In test-tube studies, thymoquinone (a compound in black seed) seemed to slow that enzyme down. If that happened in a real person, phenytoin could clear more slowly and build up in the blood, which might bring on side effects like dizziness, drowsiness, unsteady walking, slurred speech, or jerky eye movements.

Now the reassuring part: this is only a theoretical concern from lab work, and it has not been shown in people. Still, phenytoin has a narrow safety window, so even small shifts in its level can matter. Food amounts of black seed as a spice are unlikely to be an issue, but before starting a concentrated supplement, please check with your pharmacist or doctor.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang Z, Wang X, Wang Z, et al. Potential herb-drug interaction risk of thymoquinone and phenytoin. Chem Biol Interact. 2022;353:109801. PubMed
Moderate

PHENYTOIN (Dilantin)

3 of 3
Theoretically, black seed might increase or decrease levels and effects of phenytoin.
In vitro research suggests that thymoquinone, a constituent of black seed, can decrease the metabolism of phenytoin. This effect may be due to inhibition of cytochrome P450 2C9 (CYP2C9). However, animal research shows that black seed decreases the maximum concentration of and total systemic exposure to phenytoin by 57% and 87%, respectively. This seems to be related to increased clearance and steady state volume of distribution. This interaction has not been shown 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 tricky part with black seed and phenytoin (Dilantin): the research actually points in two opposite directions, so we can't say for sure which way it would go. In the test tube, thymoquinone (black seed's main compound) seemed to slow down phenytoin's breakdown, which would let levels climb. But in animals, black seed did the opposite and dropped phenytoin levels sharply. Neither has been confirmed in people.

Why this matters: phenytoin has a narrow safety window, so even small shifts count. Too much can cause dizziness, slurred speech, wobbly walking, or double vision; too little can let seizures break through. Because this is only lab and animal data, I wouldn't panic, but please check with your pharmacist or doctor before adding black seed supplements.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wang Z, Wang X, Wang Z, et al. Potential herb-drug interaction risk of thymoquinone and phenytoin. Chem Biol Interact. 2022;353:109801. PubMed
  2. Alkharfy KM, Al-Jenoobi FI, Al-Mohizea AM, et al. Effects of Lepidium sativum, Nigella sativa and Trigonella foenum-graceum on phenytoin pharmacokinetics in beagle dogs. Phytother Res. 2013;27(12):1800-4.

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

Black Seed Also Interacts With Other Medications

Black Seed has 911 moderate known drug interactions in our database — the Phenytoin one above is among them. If you take anything else, check it against the full list below.

Moderate 911 No known interaction 1,919 (incl. Phenytoin)
Taking anything else?

Check Another of Your Medications Against Black Seed

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

From our Q&A

Questions About Black Seed or Phenytoin

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Black Seed or Phenytoin, 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 Phenytoin

This page covers Black Seed only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenytoin page lists 224 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Kava (major).

By severity: 9 major · 187 moderate · 28 minor.

From our pharmacist’s overview on the Phenytoin page

“Phenytoin (Dilantin) is a seizure medicine with a narrow therapeutic index, meaning small changes in its blood level can bring seizures back or tip over into toxicity, so I treat its supplement list with real seriousness. The biggest group, 78 ingredients, piles on sedation, and alcohol, kava, and GHB all rate major for exactly that re…”

Reviewed by 2 · Jul 18, 2026

Open the Phenytoin interaction page

One more smart check

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

We hold 226 real supplement products containing Black Seed, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Black Seed. Your product may carry other ingredients that interact with Phenytoin too, on top of Black Seed — 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 Black Seed and Phenytoin 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 Black Seed
Top 25%

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

29 days ago today
Medication Phenytoin
Steady interest

#1,739 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 Black Seed

What is Black Seed?

Black Seed
  • Respiratory support (asthma, allergies, cough)
  • Digestive upset
  • Immune support
  • Blood sugar and cholesterol support
  • General inflammation

Black seed (Nigella sativa) is a traditional spice and remedy that has been studied for asthma, blood sugar, cholesterol, and blood pressure, with early research showing some promise but no firmly proven benefits. It is generally well tolerated in food amounts, but supplement-strength doses are less studied, so talk to your pharmacist or doctor before using it—especially if you are pregnant, breastfeeding, or take other medicines.

Read the full Black Seed monograph & all interactions
Medication

About Phenytoin

What Is Phenytoin Used For?

Brand names: Dilantin Kapseals, Dilantin, Di-Phen, Dilantin Infatabs, Phenytek, Dilantin injection

Phenytoin is used to treat and prevent seizures. The specific types covered depend on the formulation. Oral extended-release capsules (including Phenytek), chewable tablets (including Dilantin Infatabs and Phenytoin Infatabs), and oral suspension (including Dilantin-125) are used for tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures; most oral forms also cover prevention and treatment of seizures occurring during or after neurosurgery. Chewable tablets and some capsule formulations also cover complex partial seizures.

Parenteral (injectable) phenytoin sodium is used for generalized tonic-clonic status epilepticus (a prolonged, life-threatening seizure emergency) and for prevention and treatment of seizures during neurosurgery. The IV form can also substitute short-term for oral phenytoin when a patient cannot take it by mouth.

See full Phenytoin drug information
Keep checking

Other Drugs & Black Seed

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

0Major
911Moderate
0Minor
1,918No known interaction
911 Moderate 1,918 No interaction
Moderate

911 interactions

Showing 60 of 911 moderate interactions — see all 911 on the Black Seed page.

No interaction 1,918 drugs checked — show the list

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

Showing the 60 most looked-up of 1,918 medications checked with no known interaction — see the full Black Seed list.

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

Can you take Black Seed with Phenytoin?
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.
Why are there 3 interactions listed for Black Seed and Phenytoin?
Phenytoin belongs to more than one drug category, and Black Seed 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 Black Seed and Phenytoin 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 Phenytoin and Black Seed?

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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.