Grapefruit + Sildenafil Citrate
Sildenafil Citrate brand name: Viagra.
Sildenafil Citrate falls into 3 drug categories that Grapefruit can interact with; the most serious is rated major. Grapefruit juice can increase levels of drugs metabolized by CYP3A4.
Read the full interaction reportGrapefruit and Sildenafil Citrate
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. Sildenafil Citrate 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).
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
1 of 3Why this applies to Sildenafil Citrate
Sildenafil Citrate falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Grapefruit interacts with.
Clinical research shows that grapefruit juice can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. When taken orally, effects of grapefruit juice on CYP3A4 levels appear to last at least 48 hours. Grapefruit's ability to inhibit CYP3A4 has even been harnessed to intentionally increase levels of venetoclax, which is metabolized by CYP3A4, in an elderly patient with acute myeloid leukemia who could not afford full dose venetoclax. The lower dose of venetoclax in combination with grapefruit juice resulted in serum levels of venetoclax in the therapeutic reference range of full dose venetoclax and positive treatment outcomes for the patient.
Professional consensus recommends the consideration of patient age, existing medical conditions, additional medications, and the potential for additive adverse effects when evaluating the risks of concomitant use of grapefruit juice with any medication metabolized by CYP3A4. While all patients are at risk for interactions with grapefruit juice consumption, patients older than 70 years of age and those taking multiple medications are at the greatest risk for a serious or fatal interaction with grapefruit juice.
Well-controlled human studies have demonstrated the likely existence of this interaction.
Here's the deal with sildenafil (Viagra) and grapefruit. Your liver uses an enzyme called CYP3A4 to break sildenafil down and clear it out. Grapefruit blocks that enzyme, so the drug clears more slowly and can build up to higher levels in your blood. Sildenafil isn't a prodrug, so more drug simply means a stronger, longer-lasting effect.
In real terms, that can mean more of sildenafil's usual side effects: headache, facial flushing, a stuffy nose, dizziness, and lower blood pressure. The blood pressure drop is the big concern, especially if you take other blood pressure meds or nitrates. This effect can linger for a couple of days after grapefruit. Please check with your pharmacist or doctor before mixing the two.
- Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther 1999;66:118-27. DOI
- Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998;64:477-83. PubMed
- Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002;71:21-9. PubMed
- Fuhr U, Muller-Peltzer H, Kern R, et al. Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol 2002;58:45-53. PubMed
- Kanazawa S, Ohkubo T, Sugawara K. The effects of grapefruit juice on the pharmacokinetics of erythromycin. Eur J Clin Pharmacol 2001;56:799-803. PubMed
- Charbit, B., Becquemont, L., Lepere, B., Peytavin, G., and Funck-Brentano, C. Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine. Clin Pharmacol Ther 2002;72(5):514-523. PubMed
- Tanaka S, Uchida S, Miyakawa S, Inui N, Takeuchi K, Watanabe H, Namiki N. Comparison of inhibitory duration of grapefruit juice on organic anion-transporting polypeptide and cytochrome P450 3A4. Biol Pharm Bull. 2013;36(12):1936-41. PubMed
- Bailey DG. Predicting clinical relevance of grapefruit-drug interactions: a complicated process. J Clin Pharm Ther. 2017 Apr;42(2):125-27. PubMed
- Mouly S, Lloret-Linares C, Sellire PO, Sene D, Bergmann JF. Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort? Pharmacol Res. 2017 Apr;118:82-92. PubMed
- Loretz C, Ho MD, Alam N, Mitchell W, Li AP. Application of cryopreserved human intestinal mucosa and cryopreserved human enterocytes in the evaluation of herb-drug interactions: evaluation of CYP3A inhibitory potential of grapefruit juice and commercial f
- Long Z, Ruan M, Wu W, Zeng Q, Li Q, Huang Z. The successful combination of grapefruit juice and venetoclax in an unfit acute myeloid leukemia patient with adverse risk: A case report. Front Oncol 2022;12:912696. PubMed
SILDENAFIL (Viagra)
2 of 3Clinical research shows that grapefruit juice inhibits cytochrome P450 3A4 (CYP3A4) metabolism of sildenafil, increasing its absorption and plasma concentrations. Oral bioavailability of sildenafil can increase by 23% when administered with 500 mL of commercially available grapefruit juice.
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..
Here's the deal with grapefruit and sildenafil (Viagra). Your body uses a liver enzyme called CYP3A4 to clear sildenafil out of your system. Grapefruit slows that enzyme down, so the drug hangs around longer and your blood levels climb. Studies have shown grapefruit juice can bump sildenafil absorption up by roughly 23%, which means a stronger, more concentrated dose than you bargained for.
In practice, that can mean more of sildenafil's usual side effects: headache, facial flushing, a stuffy nose, dizziness, or a bigger drop in blood pressure. The effect is fairly modest, but it leans real rather than theoretical, so don't pair concentrated grapefruit juice with your dose without checking. An occasional bite of fruit is far less of a concern than drinking glasses of juice. Run your routine by your pharmacist or doctor first.
- Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002;71:21-9. PubMed
CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES
3 of 3Sildenafil Citrate also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.
In vitro research suggests that grapefruit juice might inhibit CYP2C9 enzymes. So far, this interaction has not been reported in humans.
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 gist with Viagra and grapefruit. Your body uses liver enzymes (including one called CYP2C9) to clear sildenafil out of your system. Lab research hints that grapefruit may slow one of these enzymes down, which could let sildenafil linger a bit longer and hit harder. If that happened, you might notice more of its usual effects, things like headache, facial flushing, a stuffy nose, dizziness, or a bigger drop in blood pressure.
That said, this is only a test-tube finding and hasn't actually been seen in people taking sildenafil. Most folks worry more about grapefruit's effect on the CYP3A4 enzyme, which is sildenafil's main route. Either way, if you enjoy grapefruit regularly, it's worth a quick chat with your pharmacist or doctor to be safe.
- 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.
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 775 major, 151 moderate, 63 minor known drug interactions in our database — the Sildenafil Citrate one above is among 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 Sildenafil Citrate
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 Sildenafil Citrate, 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? ›
- Which Medications Interact With Nitric Oxide Supplements? ›
- Grapefruit With Finasteride Interaction ›
- Can You Cut, Split Or Crush Viagra (Sildenafil Citrate)? ›
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 Sildenafil Citrate
This page covers Grapefruit only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Sildenafil Citrate page lists 160 supplements it has a documented interaction with, worst first, each one explained.
The most serious there right now: Activated Charcoal (major), American Mistletoe (major), Hawthorn (major), St. John's Wort (major) and Acacia Rigidula (moderate).
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 Sildenafil Citrate 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 Sildenafil Citrate 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.
#108 of 1,452 supplements looked up here in the last 7 days
#999 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.
About Sildenafil
What Is Sildenafil Used For?
Brand name: Viagra
Sildenafil treats two distinct conditions depending on the product. Viagra (tablet) and Vybrique (dissolving oral film) are approved for erectile dysfunction (ED) — difficulty getting or keeping an erection. Generic sildenafil tablets and oral film are also approved for ED.
Revatio and several generic sildenafil products (tablets, oral suspension, and injection) are used for pulmonary arterial hypertension (PAH) — high blood pressure in the arteries of the lungs — in adults to improve exercise ability and slow the disease from getting worse. Revatio oral suspension and injection are also approved for PAH in children ages 1 to 17.
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 “”.
775 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 775 major interactions — see all 775 on the Grapefruit page.
151 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 ›
- Hexobarbital ›
- 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 ›
Showing 60 of 151 moderate interactions — see all 151 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 ›
- Bupropion ›
- Metformin ›
- Amoxicillin ›
- Acyclovir ›
- Lisinopril ›
- Lamotrigine ›
- Amphetamine ›
- Pregabalin ›
- Gabapentin ›
- Dextroamphetamine ›
- Isotretinoin ›
- Methylene Blue ›
- Duloxetine ›
- Bisoprolol ›
- Cyclopentolate ›
- Candesartan Cilexetil ›
- Cephalexin ›
- Mannitol ›
- Roxithromycin ›
- Pegunigalsidase Alfa-iwxj ›
- Daptomycin ›
- Hexobarbitone ›
- Dexmethylphenidate ›
- Levetiracetam ›
- Mitomycin ›
- Factor 7a ›
- Minoxidil ›
- Thyroid Hormone ›
- Cefaclor ›
- Carbidopa, Levodopa ›
- Ezetimibe ›
- Levodopa ›
- Vancomycin ›
- Phenylephrine ›
- Spironolactone ›
- Dirithromycin ›
- Hethylphenidate Hcl ›
- Azelaic Acid ›
- Phentermine, Topiramate ›
- Bentoquatam ›
- Codeine Sulfate ›
- Tenecteplase ›
- Amoxicillin, Clavulanate Potassium ›
- Triptorelin ›
- Dextrothyroxine ›
- Lomustine ›
- Aspirin, Codeine Phosphate, Phenobarbital ›
- Acetylsalicylic Acid ›
- 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 Sildenafil Citrate Together: Common Questions
Can you take Grapefruit with Sildenafil Citrate?
Why are there 3 interactions listed for Grapefruit and Sildenafil Citrate?
How serious is the Grapefruit and Sildenafil Citrate interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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