Grapefruit + Hexobarbital
Hexobarbital brand names: Hexobarbital, Sombulex.
Grapefruit has a moderate interaction with Hexobarbital. Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP2C19.
Read the full interaction reportGrapefruit and Hexobarbital
Here is the interaction we found between these two, with the evidence behind it.
CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES
Why this applies to Hexobarbital
Hexobarbital falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES — the group Grapefruit interacts with.
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.
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.
Here's the simple version. Hexobarbital is an older barbiturate sleep medicine, and your body relies on a liver enzyme called CYP2C19 to break it down and clear it out. Grapefruit appears to slow that same enzyme. Since hexobarbital is an active drug (not a prodrug that needs to be switched on), blocking its breakdown could let more of it linger in your system.
In real terms, that might mean stronger or longer effects like heavy drowsiness, grogginess, dizziness, or unsteadiness. I'll be honest though: this is mostly theoretical and based on lab and weak clinical data, not strong studies on hexobarbital itself. A casual bite of grapefruit is unlikely to matter much, but regular juice could. Please run it by your pharmacist or doctor first.
- 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
- 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
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- 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.
- 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.
Grapefruit Also Interacts With Other Medications
Grapefruit has 776 major, 150 moderate, 63 minor known drug interactions in our database — the Hexobarbital one above is one of them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against Grapefruit
We haven’t checked that one against Grapefruit yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against Grapefruit. Pick one to open its full report.
Questions About Grapefruit or Hexobarbital
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 Hexobarbital, 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:
- Is Grapefruit-Flavored Drink Mix Safe With My Medications? ›
- Grapefruit With Finasteride Interaction ›
- Can You Take Candesartan And Amlodipine With Grapefruit? ›
- Can You Eat Grapefruit While Taking Zoloft (Sertraline)? ›
Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.
See Every Supplement That Interacts With Hexobarbital
This page covers Grapefruit only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hexobarbital page lists 125 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: 7 major · 100 moderate · 18 minor.
From our pharmacist’s overview on the Hexobarbital page
“A person taking hexobarbital (Sombulex), a barbiturate sedative, is already on a drug designed to slow the brain, and this supplement list deserves genuine care. Of the 125 ingredients listed, 78 are sedating in their own right, and stacking them on a barbiturate can push ordinary drowsiness toward dangerous sedation.”
Reviewed by 2 · Jul 18, 2026
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 Hexobarbital 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:
Where Grapefruit and Hexobarbital 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.
#110 of 1,452 supplements looked up here in the last 7 days
#1,931 of 2,830 medications looked up here in the last 7 days
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.
About Grapefruit
What is 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.
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.
No drugs match “”.
776 interactions
- Diltiazem ›
- Nifedipine ›
- Metronidazole ›
- Hydrocortisone ›
- Erythromycin ›
- Estradiol ›
- Lidocaine ›
- Guaifenesin ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Flurazepam ›
- Glyburide ›
- Triazolam ›
- Zopiclone ›
- Ciprofloxacin ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Doxorubicin ›
- Fluticasone ›
- Miconazole ›
- Nitrazepam ›
- Procainamide ›
- Trimipramine ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Lofepramine ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Methotrexate ›
- Ofloxacin ›
- Rifampin ›
- Sotalol ›
- Sumatriptan Succinate ›
- Testosterone Undecanoate ›
- Aripiprazole ›
- Azithromycin ›
- Caffeine (otc Drug) ›
- Ciclesonide ›
- Clobazam ›
- Clonazepam ›
- Clorazepate ›
- Cyclobenzaprine ›
- Dapsone ›
Showing 60 of 776 major interactions — see all 776 on the Grapefruit page.
150 interactions
- Diclofenac Sodium ›
- Theophylline ›
- Ibuprofen ›
- Naproxen ›
- Propranolol ›
- Levothyroxine ›
- Flurbiprofen ›
- Oxycodone ›
- Phenytoin ›
- Diclofenac Potassium ›
- Formoterol ›
- Indomethacin ›
- Acetaminophen ›
- Meloxicam ›
- Nortriptyline ›
- Bendamustine ›
- Levothyroxine Sodium ›
- Riluzole ›
- Carisoprodol ›
- Celecoxib ›
- Clozapine ›
- Diclofenac Epolamine ›
- Glipizide ›
- Irbesartan ›
- Moclobemide ›
- Nadolol ›
- Nilutamide ›
- Oxycodone Hydrochloride ›
- Piroxicam ›
- Propafenone ›
- Ropinirole ›
- Tapentadol ›
- Valsartan ›
- Abrocitinib ›
- Agomelatine ›
- Anagrelide ›
- Azilsartan ›
- Belzutifan ›
- Bendamustine Hydrochloride ›
- Brivaracetam ›
- Diclofenac ›
- Empagliflozin ›
- Fenfluamine ›
- Fezolinetant ›
- Fluvoxamine ›
- Fomoterol ›
- Gliclazide ›
- Glimepiride ›
- Ibuprofen Lysine ›
- Lesinurad ›
- Lumiracoxib ›
- Mefenamic Acid ›
- Mephenytoin ›
- Mephobarbital ›
- Mexiletine ›
- Montelukast Sodium ›
- Naproxen Sodium ›
- Nateglinide ›
- Olanzapine ›
- Paracetamol ›
Showing 60 of 150 moderate interactions — see all 150 on the Grapefruit page.
63 interactions
- Doxycycline ›
- Minocycline ›
- Tetracycline ›
- Ranitidine ›
- Triamcinolone ›
- Apomorphine ›
- Morphine Sulfate ›
- Ivermectin ›
- Betamethasone ›
- Cimetidine ›
- Digoxin ›
- Doxycycline Hyclate ›
- Prucalopride ›
- Acebutolol ›
- Clobetasol ›
- Cortisone Acetate ›
- Dabigatran ›
- Loperamide ›
- Minocycline Hydrochloride ›
- Triamcinolone Acetonide ›
- Afatinib Dimaleate ›
- Alvimopan ›
- Apomorphine Hydrochloride ›
- Avatrombopag Maleate ›
- Belinostat ›
- Betamethasone Dipropionate ›
- Betamethasone Valerate ›
- Betrixaban ›
- Chlortetracycline ›
- Danicopan ›
- Demeclocycline ›
- Dolutegravir ›
- Domperidone ›
- Doxycycline Monohydrate ›
- Doxycyline ›
- Fidaxomicin ›
- Fludrocortisone ›
- Linagliptin ›
- Loncastuximab Tesirine-lpyl ›
- Lusutrombopag ›
- Niraparib Tosylate ›
- Omacetaxine Mepesuccinate ›
- Opicapone ›
- Oxytetracycline ›
- Ranitidine Bismuth Citrate ›
- Rucaparib Camsylate ›
- Sofosbuvir ›
- Talazoparib ›
- Tenofovir Alafenamide Fumarate ›
- Vecuronium ›
- Vericiguat ›
- Vismodegib ›
- Betamethasone Dipropionate, Calcipotriene ›
- Amphotericin, Tetracycline ›
- Atropine, Morphine Sulfate ›
- Dolutegravir, Emtricitabine, Tenofovir Alafenamide ›
- Emtricitabine, Tenofovir Alafenamide Fumarate ›
- Fam-trastuzumab, Deruxtecan-nxki ›
- Ledipasvir, Sofosbuvir ›
- Linagliptin, Metformin Hydrochloride ›
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.
- Methylphenidate ›
- Metoprolol ›
- Aspirin ›
- Escitalopram ›
- Valacyclovir ›
- Docusate ›
- Hydroxyurea ›
- Methamphetamine ›
- Semaglutide ›
- Tirzepatide ›
- Lisdexamfetamine ›
- Acyclovir ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Lisinopril ›
- Lamotrigine ›
- Gabapentin ›
- Amphetamine ›
- Pregabalin ›
- Isotretinoin ›
- Dextroamphetamine ›
- Methylene Blue ›
- Duloxetine ›
- Bisoprolol ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Mannitol ›
- Cephalexin ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Dexmethylphenidate ›
- Levetiracetam ›
- Mitomycin ›
- Minoxidil ›
- Cefaclor ›
- Factor 7a ›
- Carbidopa, Levodopa ›
- Thyroid Hormone ›
- Ezetimibe ›
- Levodopa ›
- Vancomycin ›
- Phenylephrine ›
- Spironolactone ›
- Dirithromycin ›
- Hethylphenidate Hcl ›
- Phentermine, Topiramate ›
- Azelaic Acid ›
- Bentoquatam ›
- Tenecteplase ›
- Amoxicillin, Clavulanate Potassium ›
- Codeine Sulfate ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
- Acetylsalicylic Acid ›
- Aspirin, Codeine Phosphate, Phenobarbital ›
- Succimer ›
Showing the 60 most looked-up of 1,840 medications checked with no known interaction — see the full Grapefruit list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
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
Taking Grapefruit and Hexobarbital Together: Common Questions
Can you take Grapefruit with Hexobarbital?
How serious is the Grapefruit and Hexobarbital interaction?
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