High-quality clinical trials are lacking to support therapeutic applications of grapefruit and grapefruit juice. Limited data suggest potential benefit for certain patient populations in reducing the risk of renal stones and type 2 diabetes, as well as some cardiovascular risk factors (including improvement in systolic blood pressure, high-density lipoprotein [HDL] cholesterol, and arterial stiffness). Some trials also demonstrate reductions in body fat and waist circumference but data regarding use for weight loss are equivocal. Antimicrobial effects have been reported. Consumption of whole grapefruit has been shown in several analyses to provide improved benefits compared to the juice.
Quality clinical trials upon which to base therapeutic dosing recommendations for grapefruit are limited.
None well defined. In patients with major myocardial structural disorders, pink grapefruit should be avoided due to proarrhythmic effects. The potential for drug interactions with grapefruit should be considered in cases in which an increase or decrease of the coadministered drug is clinically important.
Grapefruit has "generally recognized as safe" (GRAS) status when used as food, according to the US Food and Drug Administration. Safety of amounts greater than those in foods are unproven. Consumption of grapefruit juice increases naringenin levels in breast milk.
Grapefruit juice has been reported to interact with numerous drugs.
Reports of adverse reactions associated with grapefruit consumption are limited and largely related to drug interactions. Case reports exist of allergy to pectin (a component of grapefruit) and pectin-induced asthma. Constipation and diarrhea have also been reported.
Toxicological studies on whole grapefruit are lacking. A meta-analysis of 3 landmark studies evaluating associations between grapefruit consumption and risk of breast cancer found no increased risk. The grapefruit constituent d-limonene has GRAS status. Grapefruit seed extract has been shown to be toxic to human skin fibroblast cells.
Grapefruit (C. paradisi) is a large, dimpled, round citrus fruit measuring 7.6 to 15.2 cm in diameter. It descends from a cross between a pomelo (pummelo) or shaddock (Citrus grandis), a large Malaysian citrus, and a sweet orange, and may have originated as a mutation of another type of citrus tree. The fruit grows in clusters similar to grapes, a possible origin of its name. Noteworthy cultivars of grapefruit include Duncan ("white," seeded), Marsh (seedless), Foster (pink, seeded), Thompson (pink, seedless), and redblush (red, seedless).Carper 1988, Davidson 1991, Ensminger 1993, USDA 2018
The Greek philosopher Theophrastus (371 to 287 BC), regarded as the founder of botany, wrote that "citron" could sweeten the breath and was thought to be an antidote to poison. Later, the Roman naturalist Pliny (AD 23 to 79) used the word "citrus" for the first time and labeled the fruit as a medicine. The grapefruit, known at the time as “small shaddock,” was first mentioned by Griffith Hughes (1707 to 1758) as the "forbidden fruit" of Barbados. The name "grapefruit," referring to the clusters of fruit on the trees, was said to have first been used in Jamaica in 1814. In 1823, the grapefruit was introduced in Florida by the French count Odette Phillippe, but it did not gain popularity until the end of the nineteenth century. In the 1930s, the Hollywood Diet, which recommended a limited calorie intake of approximately 800 calories per day and included grapefruit consumption at each meal, became popular. Worldwide production of grapefruit was projected in 2010 at approximately 5.5 million metric tons, and the juice of the fruit, including concentrate, accounts for approximately 42% of all US-processed grapefruit products.Carper 1988, Davidson 1991, Ensminger 1993, USDA 2018
The chemistry of grapefruit is well studied. Grapefruit is high in polyphenols, with its flavonoid naringin responsible for imparting the bitter taste. Other constituents include sugars, polysaccharides, organic acids, nitrogenous compounds, lipids, carotenoids such as beta-carotene and lycopene (that contribute to pink and red color), vitamins, minerals, flavonoids, and volatile components that contribute to aroma. Grapefruit is high in water and fiber, and contains a small amount of protein. The whole fruit is also a good source of potassium, vitamin C, inositol, bioflavonoids, and pectin; however, the juice alone is not high in pectin. Other vitamins and minerals present in grapefruit are vitamin A, thiamine, folate, vitamin B6, niacin, magnesium, calcium, and iron. The amount of vitamin A can be almost 1,000 times higher in the pink/red variations. In addition, grapefruit has minimal fat and is low in calories and sodium. The peel contains citral (an aldehyde that antagonizes the effects of vitamin A) and other terpenes (including limonene), which are of interest because of their chemoprotective and cholesterol-solvent properties.Carper 1988, Ensminger 1993, Giamperi 2004, Onakpoya 2017, Rampersaud 2017, Sun 2007
Constituents in grapefruit that affect cytochrome P450 (CYP-450) enzymes include the furanocoumarins bergamottin and 6′,7′-dihydroxybergamottin (DHB). DHB has been identified as a principal inhibitory furanocoumarin, with constituents of varying CYP3A inhibitory potencies; this effect is absent with consumption of low-furanocoumarin grapefruit juice.Kawaguchi-Suzuki 2017 Naringin and naringenin also exhibit inhibitory effects on the CYP-450 system but may inhibit CYP enzymes primarily in the intestine and less so in the liver. Concentrations of these inhibitory constituents have been shown to vary among commercially available juices; an approximately 200-fold difference in DHB has been observed among batches of grapefruit juice.Giamperi 2004, Hu 2016, van Erp 2011 Naringenin is a potent inhibitor of organic anion transporting polypeptide (OATP), and grapefruit also interferes with P-glycoprotein (P-gp) and adenosine triphosphate (ATP)–binding cassette drug transporters.Romaszko 2017, van Erp 2011
In vitro screening of a grapefruit seed extract found bactericidal activity against gram-negative and gram-positive bacteria at dilutions up to 1:512.(Heggers 2002)
In a series of case reports, chewing and swallowing 5 to 6 grapefruit seeds every 8 hours was effective against Klebsiella, Staphylococcus aureus, and Escherichia coli urinary tract infections, but not against Pseudomonas aeruginosa–resistant strains.(Oyelam 2005)
The American Urology Association's update guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome (2022) states that self-care practices and behavioral modifications that can improve symptoms should be discussed and implemented as feasible, which includes avoidance of certain foods known to be common bladder irritants like citrus products (clinical principle).(Clemens 2022)
The grapefruit constituents pectin, lycopene, and d-limonene have been evaluated for potential chemotherapeutic roles via antioxidant and apoptosis-inducing activity. Clinical trials have produced mixed results.(Giamperi 2004, Sun 2007, van Breemen 2008)
Limited clinical trials have been conducted, possibly due to the potential for drug interactions. Two trials in post–coronary bypass patients with atherosclerosis demonstrated improved lipid profiles following whole grapefruit and grapefruit juice consumption.(Gorinstein 2004, Gorinstein 2006) Antioxidant-carrying capacity also improved. Systolic and diastolic blood pressure were unchanged throughout the 30-day study.(Reshef 2005) A systematic review of randomized controlled trials reporting the effects of grapefruit on body weight and cardiovascular risk factors identified 3 studies that met inclusion criteria (N=250). All participants were overweight or obese, with a mean body mass index (BMI) ranging from 31.4 to 36.8 kg/m2. Fresh grapefruit, grapefruit juice, or grapefruit capsules, with naringin doses of the grapefruit formulations ranging from 81 to 142 mg/day, was given for either 6 or 12 weeks. A reduction in systolic blood pressure (SBP), but not diastolic blood pressure, was reported compared to controls in a meta-analysis of all 3 trials (mean difference, −2.43 mm Hg; no P value reported) but significance was lost in the sensitivity analysis; no heterogeneity was evident in either analysis. Improvement in HDL cholesterol was reported by both the overall and sensitivity analyses as being important (mean difference, +3.21 and +4.6 mg/dL, respectively); heterogeneity was moderate to high. In contrast, no difference in fasting blood glucose, total cholesterol, or low-density lipoprotein (LDL) was found. Subgroup analysis reported fresh grapefruit provides a statistically significant improvement in SBP compared with grapefruit juice (mean difference, −2.48 mm Hg; no P value provided), with low heterogeneity. HDL cholesterol was also reported as statistically significantly improved (+3.56 mg/dL); however, this was incongruent with the P value provided (P=0.06). Constipation and diarrhea were reported as adverse events in 1 trial. Overall, the quality of evidence for the studies was rated as moderate, except for the LDL and HDL results, which were considered low quality.(Onakpoya 2017)
In a randomized, double-blind, controlled, crossover trial in healthy postmenopausal women (N=48), consumption of grapefruit juice for 6 months (340 mL/day; 201 mg/day of naringenin glycosides) significantly reduced central aortic stiffness compared with placebo (P=0.019).(Habauzit 2015) Prolongation of the QTc interval has also been demonstrated in healthy volunteers, as well as in patients with cardiomyopathy, possibly due to the naringenin glycoside content.(Piccirillo 2008, Zitron 2005)
Initial animal and in vitro studies showed the capacity of d-limonene to dissolve gallstones.(Sun 2007)
Associations between fruit consumption and the risk of type 2 diabetes were assessed using data from 3 prospective longitudinal cohort studies (66,105 women in the Nurses' Health Study [1984-2008], 85,104 women in the Nurses' Health Study II [1991-2009], and 36,173 men from the Health Professionals Follow-up Study [1986-2008]). At baseline, patients did not have diabetes, cardiovascular disease, or cancer. A total of 12,198 participants developed type 2 diabetes during the 3,464,641 person-years of follow-up. The pooled hazard ratio (HR) for risk of type 2 diabetes was 0.95 (95% CI, 0.91 to 0.99) for grapefruit, with the lowest risk observed for blueberries (HR, 0.74; 95% CI, 0.66 to 0.83) and an inverse correlation observed for cantaloupe (HR, 1.1; 95% CI, 1.02 to 1.18). Associations with risk of type 2 diabetes differed significantly among individual fruits. In contrast, greater fruit juice consumption was associated with an increased risk, while substitution of whole fruits for fruit juice lowered this risk (except for strawberries and cantaloupe). Replacing 3 servings per week of grapefruit juice with whole grapefruit lowered the risk of diabetes by 12% (8% to 17%) after multifactorial adjustments, whereas the pooled analysis showed a 7% lower risk for whole fruits (1 serving of grapefruit was equal to one-half of a grapefruit); the highest reduction in diabetes risk occurred with blueberries (33%). No significant associations between risk of type 2 diabetes and total whole fruit consumption, glycemic index/glycemic load of fruits, or flavonoid subtypes were observed. The mechanism of action for grapefruit leads to improved glucose tolerance that appears to result from an increase in glucagonlike peptide 1 due to inhibition of dipeptidyl peptidase 4 by naringin, which is found in high amounts in grapefruit.(Muraki 2013)
Grapefruit has value as a dietary supplement, similar to other citrus fruits. Grapefruit juice is an excellent source of vitamin C, with the pink variation consistently ranking among the most nutrient dense. It is also a good source of potassium and provides folate, thiamine, magnesium, vitamin B6, iron, niacin, and calcium; pink and red varieties are high in vitamin A, primarily due to beta-carotene. An 8 oz serving of the juice also contains approximately 1.3 g of protein. Grapefruit juice is also rich in polyphenols, especially naringin. Caloric content is provided mostly by sugars (sucrose, fructose, glucose), with 22 g of carbohydrates delivered in an 8 oz serving of 100% juice.(Rampersaud 2017) Consumption of the whole fruit has been shown in multiple analyses to provide improved health benefits compared with consuming the juice.(Muraki 2013, Onakpoya 2017)
Vitamin C status and bleeding scores were improved in a study of patients with periodontitis who consumed 2 grapefruits a day for 2 weeks.(Staudte 2005)
Weight loss has been observed in some, but not all, clinical studies; conflicting findings could be due to variability of dosage regimens.(Fujioka 2006, Gorinstein 2006) A meta-analysis of randomized controlled trials reported the effects of grapefruit on body weight and cardiovascular risk factors in obese adults (mean BMI ranging from 31.4 to 36.8 kg/m2). A total of 3 studies were identified that met inclusion criteria (N=250) in the systematic review, all of which incorporated lifestyle modifications as part of a weight management regimen. Fresh grapefruit, grapefruit juice, or grapefruit capsules, with naringin doses of the grapefruit formulations ranging from 81 to 142 mg/day, was given for either 6 or 12 weeks. Sensitivity analyses revealed a nonsignificant reduction in body weight but found a statistically significant reduction in body fat (mean difference, −0.49%; P=0.002) and waist circumference (mean difference, −1.15 cm; P<0.0001) in favor of grapefruit over controls in overweight or obese participants. Quality of evidence for the studies was considered moderate.(Onakpoya 2017) Another systematic review pointed to preliminary data from a National Health and Nutrition Examination Survey (NHANES) analysis report that demonstrated lower body weight, BMI, and waist circumference in women who consumed any amount of grapefruit (ie, fresh, juice, frozen) compared with nonconsumers.(Rampersaud 2017)
Quality clinical trials upon which to base therapeutic dosing recommendations are limited.
1 grapefruit daily for 30 days has been used in a clinical trial to improve lipid profiles.Gorinstein 2006 Fresh grapefruit, grapefruit juice, and grapefruit capsules for 6 or 12 weeks, with naringin doses of the formulations ranging from 81 to 142 mg/day, have been used in randomized controlled trials evaluating effects on cardiovascular risk factors in obese adults.Onakpoya 2017 In a trial of healthy postmenopausal women, 340 mL/day (providing 201 mg/day of naringenin) of grapefruit juice was administered for 6 months to evaluate effects on arterial stiffness.Habauzit 2015
Pooled results from 3 prospective longitudinal cohort studies (N=187,382; 3,464,641 person-years of follow-up) reported consumption of 2 to 4 servings per week of grapefruit to reduce the risk of type 2 diabetes. In one cohort of women, 2 to 4 servings per week or 5 or more servings per week of grapefruit (1 serving of grapefruit was one-half of a grapefruit) also reduced risk.Muraki 2013
2 grapefruits per day for 2 weeks were consumed in a trial evaluating effects on vitamin C status of patients with periodontitis.Staudte 2005
8 oz (237 mL) of grapefruit juice, or half of a fresh grapefruit, 3 times a day before each meal for 12 weeks was used in a clinical trial evaluating effects on body weight and metabolic syndrome.Fujioka 2006 In a meta-analysis evaluating effects on body weight, fresh grapefruit, grapefruit juice, or grapefruit capsules (with naringin dosages of the formulations ranging from 81 to 142 mg) were administered for 6 or 12 weeks in the included randomized controlled trials.Onakpoya 2017
Grapefruit and grapefruit juice is considered GRAS for use as food. Safety of amounts greater than those in foods are unproven.Ernst 2002 Naringenin concentration has been shown to increase in human breast milk after consumption of a single 250 mL dose of grapefruit juice, with mean concentrations increasing by approximately 35% from baseline within the first 4 hours. Additionally, a low-naringenin diet that limited citrus and tomato products reduced naringenin levels in breast milk.Romaszko 2017
Grapefruit seed extract is not the equivalent of grapefruit juice, and it is not known whether extracts of grapefruit seed also have potential to alter drug metabolism. Grapefruit may interact with medications via mechanisms including inhibition of CYP3A4, CYP1A2, CYP2A6, P-gp, ATP-binding cassette drug transporters, and uptake transporters such as OATPs.(Seden 2010, van Erp 2011)
CYP inhibition appears to occur predominantly via intestinal enzymes and less so via the hepatic system.(Hu 2016, van Erp 2011) Studies have indicated an approximate 12-hour half-life of CYP enzyme inhibition, with a mean 62% inhibition still present 5 days after grapefruit consumption.(Cohen 2012) The inhibitory effect of grapefruit juice on the CYP1A2 isozyme appears to be weak and uncertain as reflected by equivocal results in pharmacokinetic studies using the substrates caffeine and theophylline. Adding to the uncertainty is the wide variation in inhibitory flavonoids that occurs among grapefruit juice preparations.(Hu 2016) Grapefruit juice with concentrations of bergamotten and DHB selected specifically to induce a clinically relevant effect on CYP3A4 with the substrate sunitinib were measured to be at least 23.5 and 2.7 mcmol/L, respectively.(van Erp 2011)
Abemaciclib: Grapefruit juice may increase the serum concentration of abemaciclib. Avoid combination.(Verzenio 2018)
Acalabrutinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of acalabrutinib.(Calquence 2017)
Albendazole: Grapefruit juice may increase serum concentrations of the active metabolite(s) of albendazole. Monitor therapy.(Nagy 2002)
Alprazolam: Grapefruit juice may increase the serum concentration of alprazolam. No action needed.(Yasui 2000)
Antifungal agents (azole derivatives, systemic): Grapefruit juice may increase the serum concentration of antifungal agents (azole derivatives, systemic). This specifically applies to oral antifungal administration, and the interaction may be different depending on the specific dosage form being used. Monitor therapy.(Gubbins 2004, Gubbins 2008, Kawakami 1998, Penzak 1999)
Aprepitant: CYP3A4 inhibitors (moderate) may increase the serum concentration of aprepitant. Avoid combination.(Emend 2015)
Aripiprazole: CYP3A4 inhibitors (moderate) may increase the serum concentration of aripiprazole. Monitor therapy. Aripiprazole dose reductions may be recommended with concomitant use of a CYP2D6 inhibitor. Aripiprazole dose reductions may be recommended in CYP2D6 "poor metabolizers." See full product monograph for genotype-based dosing information. Aripiprazole dose reduction is not recommended when used as adjunctive therapy for major depressive disorder.(Abilify February 2011, Abilify Maintana February 2013, Aung 2010, Azuma 2012, Kubo 2005)
Artemether and lumefantrine: Grapefruit juice may increase serum concentrations of the active metabolite(s) of artemether and lumefantrine. Specifically, concentrations of dihydroartemisinin (DHA), the active metabolite of artemether may be increased. Grapefruit juice may increase the serum concentration of artemether and lumefantrine. Monitor therapy.(Coartem August 2019, Lefevre 2002, van Agtmael 1999, van Agtmael 1999)
Asunaprevir: CYP3A4 inhibitors (moderate) may increase the serum concentration of asunaprevir. Avoid combination.(Sunvepra 2016)
Avanafil: CYP3A4 inhibitors (moderate) may increase the serum concentration of avanafil. Consider therapy modification.(Stendra August 2018)
Benzhydrocodone: CYP3A4 inhibitors (moderate) may increase the serum concentration of benzhydrocodone. Specifically, the concentration of hydrocodone may be increased. Monitor therapy.(Apadaz February 2018, Viekira Pak June 2016)
Bilastine: Grapefruit juice may decrease the serum concentration of bilastine. Monitor therapy.(Ilaxten January 2012)
Blonanserin: CYP3A4 inhibitors (moderate) may increase the serum concentration of blonanserin. Monitor therapy.(Lonasen 2014, Shang 2017)
Brexpiprazole: CYP3A4 inhibitors (moderate) may increase the serum concentration of brexpiprazole. Monitor therapy. Brexpiprazole dose reductions are recommended with concomitant use of both a CYP3A4 inhibitor and a moderate or strong CYP2D6 inhibitor. If brexpiprazole is used with a moderate CYP3A4 inhibitor in a patient who is a CYP2D6 poor metabolizer (ie, deficient CYP2D6 activity), the brexpiprazole dose should be reduced to 25% of the usual dose.(Rexulti July 2015)
Brigatinib: Grapefruit juice may increase the serum concentration of brigatinib. Avoid combination.(Alunbrig April 2017)
Cannabis: CYP3A4 inhibitors (moderate) may increase the serum concentration of cannabis. More specifically, tetrahydrocannabinol and cannabidiol serum concentrations may be increased. Monitor therapy. This interaction is mainly expected when physiologically significant amounts of tetrahydrocannabinol (THC, the major known psychoactive component of cannabis) are introduced systemically. While this encompasses the vast majority of medical and recreational cannabis use, some cannabis strains, products, and routes of administration specifically (and often intentionally) minimize systemic THC exposure. While cannabidiol concentrations are also likely increased by CYP3A4 inhibition, the clinical significance of this increase is less clear.(Sativex 2014, Watanabe 2007)
Carbamazepine: Grapefruit juice may decrease the metabolism of carbamazepine. Monitor therapy.(Bonin 2001, Garg 1998, Ho 2001)
Ceritinib: Grapefruit juice may increase the serum concentration of ceritinib. Avoid combination.(Zykadia March 2019)
Cilostazol: CYP3A4 inhibitors (moderate) may increase the serum concentration of cilostazol. Consider therapy modification.(Pletal July 2015, Suri 1999, Taniguchi 2007)
Clomipramine: Grapefruit juice may increase the serum concentration of clomipramine. Monitor therapy.(Oesterheld 1997)
Cobimetinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of cobimetinib. Avoid combination.(Cotellic Novembe 2015)
Crizotinib: Grapefruit juice may increase the serum concentration of crizotinib. Avoid combination.(Xalkori September 2021)
CYP3A4 substrates (high risk with inhibitors): CYP3A4 inhibitors (moderate) may decrease the metabolism of CYP3A4 substrates (high risk with inhibitors). Monitor therapy.(Bjornsson 2003, Kawaguchi-Suzuki 2017)
Dasatinib: Grapefruit juice may increase the serum concentration of dasatinib. Avoid combination.(Johnson 2010, Sprycel November 2017)
Deflazacort: Grapefruit juice may increase the serum concentration of deflazacort. Avoid combination.(Emflaza June 2021)
Docetaxel (oral): Grapefruit juice may reduce the clearance and increase the serum concentration of docetaxel (oral). Monitor closely.(Valenzuela 2011)
Dronabinol: CYP3A4 inhibitors (moderate) may increase the serum concentration of dronabinol. Monitor therapy.(Sativex February 2014, Watanabe 2007)
Dronedarone: Grapefruit juice may increase the serum concentration of dronedarone. Avoid combination.(Multaq March 2014)
Efonidipine: Grapefruit Juice may increase the serum concentration of efonidipine. Monitor therapy.(Uesawa 2008)
Eletriptan: CYP3A4 inhibitors (moderate) may increase the serum concentration of eletriptan. Consider therapy modification.(Relpax November 2013)
Elexacaftor/Tezacaftor/Ivacaftor: Grapefruit juice may increase the serum concentration of elexacaftor, tezacaftor, and ivacaftor. Specifically, the serum concentration of ivacaftor may be increased. Avoid combination.(Trikafta October 2019)
Encorafenib: Grapefruit juice may increase the serum concentration of encorafenib. Avoid combination.(Braftovi April 2020)
Entrectinib: Grapefruit Juice may increase the serum concentration of entrectinib. Avoid combination.(Rozlytrek August 2019)
Eplerenone: CYP3A4 inhibitors (moderate) may increase the serum concentration of eplerenone. Consider therapy modification. Dosing recommendations may vary depending on indication and international labeling.(Inspra May 2016, Inspra June 2014)
Etoposide: Grapefruit Juice may decrease the serum concentration of etoposide. Monitor therapy. This interaction only applies to orally administered etoposide.(Bailey 2010, Reif 2002)
Fentanyl: Grapefruit juice may increase the serum concentration of fentanyl. No action required. In a pharmacokinetic study of 12 healthy volunteers, coadministration of grapefruit juice (250 mL of regular strength the evening before, followed by 100 mL of double strength the following morning) and oral transmucosal fentanyl lozenge (10 mcg/kg given 1 hour after grapefruit juice) had no effect on the maximum serum concentration, AUC, or clearance of fentanyl. (Kharasch 2004) Grapefruit juice is typically considered a moderate CYP3A4 inhibitor, but because it only inhibits intestinal CYP3A4 and has little effect on hepatic CYP3A4, it is unlikely to affect concentrations of fentanyl, a drug that is administered via non-oral routes (ie, intravenous, transmucosal, transdermal, intranasal, sublingual).(Greenblatt 2003, Kupferschmidt 1995, Lown 1997, Lundahl 1997)
Flibanserin: CYP3A4 inhibitors (moderate) may increase the serum concentration of flibanserin. Avoid combination.(Addyi 2015)
Fluvoxamine: Grapefruit juice may increase the serum concentration of fluvoxamine. Monitor therapy.(Hori 2003)
Fosaprepitant: CYP3A4 Inhibitors (moderate) may increase the serum concentration of fosaprepitant. Avoid combination.(Emend April 2018)
Guanfacine: CYP3A4 inhibitors (moderate) may increase the serum concentration of guanfacine. Consider therapy modification.(Intuniv July 2016)
Halofantrine: CYP3A4 inhibitors (moderate) may increase the serum concentration of halofantrine. Consider therapy modification.(Baune 1999, Charbit 2002, Halfan October 2001)
Hormonal contraceptives: Grapefruit juice may increase the serum concentration of hormonal contraceptives. No action needed. This interaction only applies to orally administered hormonal contraceptives.(Chateal EQ June 2021, NuvaRing January 2020, Taysofy May 2021, Weber 1996)
Hydrocodone: CYP3A4 inhibitors (moderate) may increase the serum concentration of hydrocodone. Monitor therapy. The significance of this interaction may be greater in patients who are also receiving a CYP2D6 inhibitor or with use of a CYP3A4 inhibitor that also inhibits CYP2D6, as CYP2D6 is partially responsible for hydrocodone metabolism.(Zohydro August 2014)
Ifosfamide: CYP3A4 inhibitors (moderate) may decrease serum concentrations of the active metabolite(s) of ifosfamide. Monitor therapy.(Ifex March 2012, Kerbusch 2001, McCune 2005)
Ibrutinib: Grapefruit juice may increase the serum concentrations of ibrutinib. Avoid combination.(de Jong 2015, Imbruvica August 2017)
Imatinib: Grapefruit juice may increase the serum concentration of imatinib. Avoid combination.(Gleevec August 2020, Kimura 2011)
Indinavir: Grapefruit juice does not appear to affect serum concentration of indinavir. No known interaction.(Penzak 2002, Shelton 2001)
Itraconazole: Grapefruit juice may decrease the serum concentration of itraconazole. Grapefruit juice may increase the serum concentration of itraconazole. Monitor therapy.(Gubbins 2004, Gubbins 2008, Kawakami 1998, Penzak 1999)
Ivabradine: Grapefruit juice may increase the serum concentration of ivabradine. Avoid combination.(Corlanor May 2019)
Ivosidenib: CYP3A4 inhibitors (moderate) may increase the serum concentration of ivosidenib. Consider therapy modification.(Tibsovo 2018)
Ketamine: Grapefruit juice may increase the serum concentration of ketamine. Monitor therapy. This interaction is only expected to occur when ketamine is administered orally. No interaction is anticipated when ketamine is administered via routes that bypass the gastrointestinal tract (eg, intravenous, nasal).(Peltoniemi 2012)
Lacidipine: Grapefruit juice may increase the serum concentration of lacidipine. Avoid combination.(Motens 2013, Vaxar August 2014)
Lapatinib: Grapefruit juice may increase the serum concentration of lapatinib. Avoid combination.(Smith 2009, Tykerb December 2018)
Larotrectinib: Grapefruit juice may increase the serum concentration of larotrectinib. Consider therapy modification.(Vitrakvi November 2018)
Lefamulin: CYP3A4 inhibitors (moderate) may increase the serum concentration of lefamulin. Monitor therapy. This information is specific for the oral formulation of lefamulin. No clinical action is likely needed for coadministration of IV lefamulin and moderate CYP3A4 inhibitors.(Xelenta August 2019)
Lercanidipine: Grapefruit juice may increase the serum concentration of lercanidipine. Avoid combination.(Lercanidipine November 2013)
Lomitapide: CYP3A4 inhibitors (moderate) may increase the serum concentration of lomitapide. Avoid combination.(Juxtapid December 2012)
Lurasidone: Grapefruit juice may increase the serum concentration of lurasidone. Avoid combination.(Latuda July 2013)
Manidipine: CYP3A4 inhibitors (moderate) may increase the serum concentration of manidipine. Monitor therapy.(Uno 2006)
Methadone (oral): Grapefruit juice may decrease the CYP3A4-induced metabolite of methadone (2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP]), with minimal effects on serum concentrations and clearance. Consider this when monitoring EDDP for compliance.(Feng 2017)
Mifepristone: Grapefruit juice may increase the serum concentration of mifepristone. Avoid combination. Avoidance of this combination is only recommended by the manufacturer of a multiple-dose mifepristone product used for treatment of hyperglycemia in Cushing's syndrome.(Korlym November 2019, Mifeprex April 2019, Nguyen 2017)
Mirodenafil: Grapefruit juice may increase the serum concentration of mirodenafil. Avoid combination.(Mvix April 2016, Shin 2009)
Montelukast: Grapefruit juice may increase the serum concentration of montelukast. Avoid combination.(Cingi 2013)
Naldemedine: CYP3A4 inhibitors (moderate) may increase the serum concentration of naldemedine. Monitor therapy.(Symproic March 2017)
Nalfurafine: CYP3A4 inhibitors (moderate) may increase the serum concentration of nalfurafine. Monitor therapy.(Ando 2012, Ramitch May 2017)
Naloxegol: Grapefruit juice may increase the serum concentration of naloxegol. Avoid combination.(Movantik September 2014)
Neratinib: CYP3A4 inhibitors (moderate) may increase the serum concentration of neratinib. Avoid combination.(Abbas 2011, Nerlynx July 2017)
Nicardipine: Grapefruit juice may increase the serum concentration of nicardipine. Monitor therapy. This interaction likely only applies to orally administered nicardipine.(Ohnishi 2006, Uesawa 2008, Uno 2000)
Nilotinib: Grapefruit juice may increase the serum concentration of nilotinib. Monitor therapy.(Tasigna July 2018, Yin 2010)
Nimodipine: Grapefruit juice may increase the serum concentration of nimodipine. Avoid combination.(Fuhr 1998, Nymalize May 2013)
Nitrendipine: Grapefruit juice may increase the serum concentration of nitrendipine. Monitor therapy.(Ohnishi 2006, Soons 1991, Uesawa 2008)
Olaparib: Grapefruit juice may increase the serum concentration of olaparib. Avoid combination.(Dirix 2016, Lynparza January 2018)
Palovarotene: Grapefruit juice may increase the serum concentration of palovarotene. Avoid combination.(Sohonos January 2022)
Panobinostat: Grapefruit juice may increase the serum concentration of panobinostat. Avoid combination.(Farydak February 2015, Hamberg 2011)
Pazopanib: Grapefruit juice may increase the serum concentration of pazopanib. Avoid combination.(Votrient October 2009)
Pexidartinib: Grapefruit juice may increase the serum concentration of pexidartinib. Avoid combination.(Turalio August 2019, Zahir 2022)
Pomalidomide: P-gp/ABCB1 inhibitors may increase the serum concentration of pomalidomide. Avoid combination.(Pomalyst February 2013)
Prasugrel: Grapefruit juice may decrease serum concentrations of the active metabolite(s) of prasugrel. No action needed.(Effient July 2009, Holmberg 2015)
Praziquantel: Grapefruit juice may increase the serum concentration of praziquantel. Monitor therapy.(Biltricide January 2019, Castro 2002)
Propafenone: CYP3A4 inhibitors (moderate) may increase the serum concentration of propafenone. Monitor therapy. Concurrent use of a CYP2D6 inhibitor should be avoided in patients receiving proprafenone and a CYP3A4 inhibitor. Patients with genetically deficient CYP2D6 activity should avoid this combination.(Rythmol SR November 2011)
Prucalopride: P-gp/ABCB1 inhibitors may increase the serum concentration of prucalopride. Monitor therapy.(Resotran December 2011)
Radotinib: Grapefruit juice may increase the serum concentration of radotinib. Avoid combination.(Supect September 2014)
Regorafenib: Grapefruit juice may decrease serum concentrations of the active metabolite(s) of regorafenib. Grapefruit juice may increase the serum concentration of regorafenib. Avoid combination.(Stivarga June 2020)
Repaglinide: Grapefruit juice may increase the serum concentration of repaglinide. No action needed.(Bidstrup 2006)
Ribociclib: Grapefruit juice may increase the serum concentration of ribociclib. Avoid combination.(Kisqali July 2020, Samant 2020)
Rivaroxaban: P-gp/ABCB1 inhibitors may increase the serum concentration of rivaroxaban. Monitor therapy.(Kubitza 2008, Xarelto September 2008)
Ruxolitinib: Grapefruit juice may increase the serum concentration of ruxolitinib. Consider therapy modification. Grapefruit juice should be avoided in patients receiving ruxolitinib doses of 5 mg daily. Initiation of ruxolitinib for treatment of myelofibrosis should be avoided in patients with platelet counts less than 50*109/L consuming grapefruit juice.(Jakafi November 2011, Shi 2012)
Salmeterol: CYP3A4 inhibitors (moderate) may increase the serum concentration of salmeterol. Monitor therapy.(Manchee 1996, Serevent March 2008)
Saxagliptin: CYP3A4 inhibitors (moderate) may increase the serum concentration of saxagliptin. Monitor therapy.(Onglyza July 2009, Patel 2011)
Sertraline: Grapefruit juice may increase the serum concentration of sertraline. Monitor therapy.(Lee 1999, Ueda 2009)
Sildenafil: Grapefruit juice may increase the serum concentration of sildenafil. Monitor therapy. This interaction only applies to orally administered sildenafil.(Jetter 2002, Lee 2001, Sheu 2003)
Silodosin: P-gp/ABCB1 inhibitors may increase the serum concentration of silodosin. Avoid combination.(Rapaflo September 2008)
Simeprevir: CYP3A4 inhibitors (moderate) may increase the serum concentration of simeprevir. Avoid combination.(Olysio November 2013)
Sirolimus (conventional): Grapefruit juice may increase the serum concentration of sirolimus. Avoid combination.(Cohen 2012, Rapamune April 2017)
Sonidegib: CYP3A4 inhibitors (moderate) may increase the serum concentration of sonidegib. Consider therapy modification.(Odomzo July 2015)
Sunitinib: Grapefruit juice may increase the serum concentration of sunitinib. No action needed.(van Erp 2011)
Suvorexant: CYP3A4 inhibitors (moderate) may increase the serum concentration of suvorexant. Consider therapy modification.(Belsomra August 2014)
Temsirolimus: Grapefruit Juice may increase serum concentrations of the active metabolite(s) of temsirolimus. Specifically, concentrations of sirolimus may be increased. No action needed.(Boni 2008, Greenblatt 2003, Lown 1997, Lundahl 1997, Torisel March 2018)
Tetrahydrocannabinol: CYP3A4 inhibitors (moderate) may increase the serum concentration of tetrahydrocannabinol. Monitor therapy.(Stott 2013, Watanabe 2007)
Tezacaftor: CYP3A4 inhibitors (moderate) may increase the serum concentration of tezacaftor. Consider therapy modification.(Symdeko June 2019)
Tezacaftor/Ivacaftor: Grapefruit juice may increase the serum concentration of tezacaftor and ivacaftor. Avoid combination.(Symdeko June 2019)
Ticagrelor: Grapefruit juice may increase the serum concentration of ticagrelor. Monitor therapy.(Holmberg 2013)
Tolvaptan: CYP3A4 inhibitors (moderate) may increase the serum concentration of tolvaptan. Avoid combination.(Jynarque April 2018, Samsca May 2009)
Toremifene: Grapefruit juice may increase the serum concentration of toremifene. Avoid combination.(Fareston March 2011)
Udenafil: CYP3A4 inhibitors (moderate) may increase the serum concentration of udenafil. Monitor therapy.(Shin 2010, Udenafil September 2014)
Ulipristal: CYP3A4 inhibitors (moderate) may increase the serum concentration of ulipristal. Avoid combination. Significance of this interaction is greater when ulipristal is used for treatment of uterine fibroid signs/symptoms (Canadian indication).(ella August 2010, Fibristal June 2013, Pohl 2013)
Venetoclax: Grapefruit juice may increase the serum concentration of venetoclax. Avoid combination.(Venclexta April 2016)
Verapamil: Grapefruit juice may increase the serum concentration of verapamil. Monitor therapy.(Fuhr 2002, Ho 2000, Zaidenstein 1998)
Vilazodone: CYP3A4 inhibitors (moderate) may increase the serum concentration of vilazodone. Monitor therapy.(Boinpally 2014, Viibryd January 2011)
Vincristine (liposomal): P-gp/ABCB1 inhibitors may increase the serum concentration of vincristine (liposomal). Avoid combination.(Marqibo August 2012)
Voclosporin: Grapefruit juice may increase the serum concentration of voclosporin. Avoid combination.(Ling 2014, Lupkynis January 2021)
Zuclopenthixol: CYP3A4 inhibitors (moderate) may increase the serum concentration of zuclopenthixol. Monitor therapy. Interaction most likely applies to poor CYP2D6 metabolizers or with use of strong CYP2D6 inhibitors.(Clopixol January 2011, Davies 2010)
Grapefruit juice interacts with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, amiodarone, and warfarin; avoid use in patients with heart failure.(Page 2016)
Some studies have reported clinically unimportant pharmacokinetic drug interactions with natural products. Limited information as well as potentially high interpatient variability in clinical response warrants cautious interpretation and/or application of these data in practice.
Fentanyl (transmucosal): Grapefruit juice minimally affected maximum plasma concentration, time to maximum plasma concentration, area under the curve (AUC), and maximal pupil diameter change after administration of oral transmucosal fentanyl. The onset or magnitude of analgesia was deemed unlikely to be affected by CYP3A-related drug interactions when treating breakthrough pain, particularly if careful attention is paid to minimal swallowing and maximal mucosal absorption.(Feng 2017)
Midazolam: Compared with regular grapefruit juice, low-furanocoumarin grapefruit juice was demonstrated to have no clinically relevant interaction on midazolam metabolism.(Kawaguchi-Suzuki 2017)
Nadolol: Grapefruit juice had no effect on the elimination half-life of nadolol and a nonstatistically significant decrease on AUC in healthy volunteers.(Misaka 2013)
Reports of adverse reactions related to grapefruit consumption are limited. Grapefruit juice has been associated with hypotensionOnakpoya 2017, Reshef 2005 and deep vein thrombosis (presumed to be due to an interaction with ethinyl estradiol).Grande 2009 Prolongation of the QTc interval has been demonstrated in healthy volunteers and patients with cardiomyopathy.Piccirillo 2008, Zitron 2005 Case reports of allergy to pectin and pectin-induced asthma exist.Ferdman 2006 Constipation and diarrhea have also been reported in one trial.Onakpoya 2017
Data collected between 2004 and 2013 from 8 US centers in the Drug-induced Liver Injury Network revealed that 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements, whereas 85% (709) of cases were related to prescription medications. Of the 130 cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanics/Latinos compared with non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the proportion of severe liver injury cases was significantly higher for supplements than for conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, 175 had identifiable ingredients, of which grapefruit was among the 32 (18%) single-ingredient products.Navarro 2014
Toxicological studies on whole grapefruit are lacking. A meta-analysis of 3 landmark studies evaluating associations between grapefruit consumption and risk of breast cancer (European Prospective Investigation into Cancer and Nutrition [EPIC], the Nurses' Health Study, and the Multiethnic Cohort Study of Diet and Cancer) found no increased risk of breast cancer (HR, 1.06 [95% CI, 0.95 to 1.19]); however, the possibility of an association could not be ruled out.Kim 2008, Monroe 2007, Spencer 2009 The grapefruit constituent d-limonene has GRAS status.Sun 2007 Grapefruit seed extract has been shown to be toxic to human skin fibroblast cells up to concentrations of 1:128 but not 1:512 in antibacterial studies.Heggers 2002
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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