Skip to Content

Grapefruit and Grapefruit Juice

Scientific Name(s): Citrus paradisi Macfad.
Common Name(s): Grapefruit

Clinical Overview

Use

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.

Dosing

Quality clinical trials upon which to base therapeutic dosing recommendations for grapefruit are limited.

Cardiovascular risk factors: 1 grapefruit daily for 30 days has been used in a clinical trial to improve lipid profiles. 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. 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.

Diabetes risk: 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.

Periodontitis: 2 grapefruits per day for 2 weeks were consumed in a trial evaluating effects on vitamin C status of patients with periodontitis.

Weight and related parameters: 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. 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.

Contraindications

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.

Pregnancy/Lactation

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.

Interactions

Grapefruit juice has been reported to interact with numerous drugs; however, case reports of clinically important interactions are rare.

Adverse Reactions

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.

Toxicology

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.

Botany

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

History

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

More recently, seed extracts have been used by the cosmetic and food industries.Onakpoya 2017

Chemistry

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

Uses and Pharmacology

Antimicrobial effects

In vitro data

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

Clinical data

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

Cancer

In vitro data

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

Cardiovascular risk factors

Clinical data

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

Cholelithiasis/Nephrolithiasis

Animal and in vitro data

Initial animal and in vitro studies showed the capacity of d-limonene to dissolve gallstones.Sun 2007

Clinical data

Limited human studies have confirmed this effect.Sun 2007 Decreased potential for renal stone formation has been suggested, but is debatable based on studies demonstrating that consumption of grapefruit juice increases the excretion of citrate, calcium, and magnesium similarly to acute loads of orange and apple juice.Goldfarb 2001, Honow 2003, Trinchieri 2002 No additional studies were subsequently identified for inclusion in a systematic review conducted by the CLU Working Group, which investigated dietary treatment of urinary risk factors for renal stone formation. Similar to other citrus fruits, grapefruit and its juice increase citrate excretion and have the potential to reduce the risk of stone formation in renal stone formers with hypocitraturia. However, the additional increase in oxalate excretion caused by grapefruit consumption is offset by the increase in citrate excretion.Prezioso 2015

Diabetes mellitus

Clinical data

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

Nutritional supplement

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

Periodontitis

Clinical data

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

Clinical data

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

Dosing

Quality clinical trials upon which to base therapeutic dosing recommendations are limited.

Cardiovascular risk factors

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

Diabetes risk

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

Periodontitis

2 grapefruits per day for 2 weeks were consumed in a trial evaluating effects on vitamin C status of patients with periodontitis.Staudte 2005

Weight and related parameters

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

Pregnancy / Lactation

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

Interactions

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

Albendazole: Grapefruit juice may increase serum concentrations of the active metabolite(s) of albendazole. Monitor therapy.Nagy 2002

Aliskiren: Grapefruit juice may decrease the serum concentration of aliskiren. Consider therapy modification.Glaeser 2007, Satoh 2005, Tapaninen 2010, Tekturna August 2010, Vaidyanathan 2008

Amiodarone: Grapefruit juice may decrease serum concentrations of the active metabolite(s) of amiodarone. Grapefruit juice may increase the serum concentration of amiodarone. Avoid combination.Cordarone December 2008, Libersa 2000

Amlodipine: Grapefruit juice may increase the serum concentration of amlodipine. Monitor therapy.Josefsson 1996, Josefsson 2002, Ohnishi 2006, Uesawa 2008, Vincent 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

Aripiprazole: CYP3A4 inhibitors (moderate) may increase the serum concentration of aripiprazole. Monitor therapy.Abilify February 2011, Aung 2010, Azuma 2012, Kubo 2005

Artemether: Grapefruit juice may increase the serum concentration of artemether. Monitor therapy.Coartem April 2009, El-Lakkany 2004, van Agtmael 1999a, van Agtmael 1999b

Avanafil: CYP3A4 inhibitors (moderate) may increase the serum concentration of avanafil. Consider therapy modification.Stendra April 2012

Axitinib: Grapefruit juice may increase the serum concentration of axitinib. Avoid combination.Inlyta January 2012, Pithavala 2012

Benzodiazepines (metabolized by oxidation): Grapefruit juice may decrease the metabolism of benzodiazepines (metabolized by oxidation) and their metabolites. Consider therapy modification.Hukkinen 1995, Kawaguchi-Suzuki 2017, Kupferschmidt 1995

Bosutinib: CYP3A4 inhibitors (moderate) and P-gp/ABCB1 inhibitors may increase the serum concentration of bosutinib. Avoid combination.Abbas 2011, Bosulif September 2012

Budesonide (systemic, oral inhalation): Grapefruit juice may increase the serum concentration of budesonide (systemic, oral inhalation). Avoid combination.Entocort June 2009, Pulmicort July 2010, Seidegard 2009

Buspirone: Grapefruit juice may decrease the metabolism of buspirone. Consider therapy modification.Lilja 1998

Cabozantinib: Grapefruit juice may increase the serum concentration of cabozantinib. Avoid combination.Cometriq December 2012

Carbamazepine: Grapefruit juice may decrease the metabolism of carbamazepine. Monitor therapy.Bonin 2001, Garg 1998

Cisapride: Grapefruit juice may increase the serum concentration of cisapride. Consider therapy modification.Desta 2001, Gross 1999, Kivisto 1999, Offman 2001

Clomipramine: Grapefruit juice may increase the serum concentration of clomipramine. Monitor therapy.Oesterheld 1997

Clopidogrel: Grapefruit juice may decrease the effect of clopidogrel. Avoid combination.Holmberg 2014

Colchicine: CYP3A4 inhibitors (moderate) and P-gp/ABCB1 inhibitors may increase the serum concentration of colchicine. Colchicine distribution into certain tissues (eg, brain) may also be increased. Consider therapy modification.Akdag 2006, Caraco 1992, Cheng 2005, Colcrys July 2009, Dogukan 2001, Dupont 2002, Eleftheriou 2008, Gruberg 1999, Hung 2005, Menta 1987, Noppen 1987, Rieger 1990, Rollot 2004, Rumpf 1990, Troger 2005, van der Velden 2008, Yussim 1994 In a small study evaluating pharmacokinetic values following a single dose of colchicine, increased colchicine levels in subjects receiving grapefruit juice 240 mL twice daily for 4 days were not observed.Wason 2012

Cortisone: Grapefruit juice may increase cortisol serum levels. Monitor therapy.Methlie 2011

Crizotinib: Grapefruit juice may increase the serum concentration of crizotinib. Avoid combination.Xalkori August 2011

Cyclosporine (systemic): Grapefruit juice may decrease the metabolism of cyclosporine (systemic). Consider therapy modification.Bistrup 2001, Brunner 1998, Brunner 2000, Ducharme 1993, Ducharme 1995, Edwards 1993, Edwards 1998, Hermann 2002, Hollander 1995, Ioannides-Demos 1997, Ku 1998, Lee 2001, Mehrsai 2003, Min 1996, Proppe 1996, Yee 1994, Yee 1995, Yee 1997

CYP3A4 substrates: CYP3A4 inhibitors (moderate) may decrease the metabolism of CYP3A4 substrates. Monitor therapy.Bjornsson 2003, Kawaguchi-Suzuki 2017

Dabigatran etexilate: P-gp/ABCB1 inhibitors may increase serum concentrations of the active metabolite(s) of dabigatran etexilate. Consider therapy modification.Pradax January 2012, Pradaxa November 2011

Diltiazem: Grapefruit juice may increase the serum concentration of diltiazem. Monitor therapy.Christensen 2002, Ohnishi 2006, Sigusch 1994

Docetaxel (oral): Grapefruit juice may reduce the clearance and increase the serum concentration of docetaxel (oral). Monitor closely.Valenzuela 2011

Dronedarone: Grapefruit juice may increase the serum concentration of dronedarone. Avoid combination.Multaq June 2009

Eplerenone: CYP3A4 inhibitors (moderate) may increase the serum concentration of eplerenone. Consider therapy modification.Inspra June 2012, Inspra August 2012

Everolimus: Grapefruit juice may increase the serum concentration of everolimus. Avoid combination.Afinitor October 2010, Zortress March 2010

Felodipine: Grapefruit juice may increase the serum concentration of felodipine. Consider therapy modification.Bailey 1991, Bailey 1993, Bailey 1995, Bailey 1996, Bailey 2000, Dresser 2000, Edgar 1992, Goosen 2004, Kakar 2004, Lown 1997, Lundahl 1995, Lundahl 1997, Malhotra 2001, Paine 2006, Plendil June 2008, Uesawa 2008

Fentanyl: CYP3A4 inhibitors (moderate) may increase the serum concentration of fentanyl. Consider therapy modification.Bower 1982, Hallberg 2006, Ibrahim 2003, ISMP 2008, Mercadante 2002, Olkkola 1999, Palkama 1998, Raucoules-Aime 1997, Saari 2008

Fexofenadine: Grapefruit juice may decrease the serum concentration of fexofenadine. Monitor therapy.Allegra July 2007, Bailey 2007, Cvetkovic 1999, Dresser 2002, Glaeser 2007

Fluvoxamine: Grapefruit juice may increase the serum concentration of fluvoxamine. Monitor therapy.Hori 2003

Halofantrine: CYP3A4 inhibitors (moderate) may increase the serum concentration of halofantrine. Consider therapy modification.Baune 1999a, Baune 1999b, Halfan October 2001, Halliday 1995, Khoo 1998

HMG-CoA reductase inhibitors: Grapefruit juice may increase the serum concentration of HMG-CoA reductase inhibitors. Consider therapy modification.Ando 2005, Butterweek 2009, Edwards 1996, Fukazawa 2004, Holtzman 2006, Kantola 1998, Lilja 1998, Lilja1998, Lilja 1999, Lilja 2000, Lilja 2004, Lipitor June 2009, Mercadante 2002, Mevacor May 2010, Omar 2001, Paine 2005, Schmiedlin 1997, Zocor June 2011

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 (oral): Grapefruit juice may increase the absolute bioavailability and serum concentrations of ibrutinib. Monitor therapy.de Vries 2016

Ivabradine: Grapefruit juice may increase the serum concentration of ivabradine. Consider therapy modification.Procoralan August 2010

Ivacaftor: Grapefruit juice may increase the serum concentration of ivacaftor. Avoid combination.Kalydeco January 2012

Lapatinib: Grapefruit juice may increase the serum concentration of lapatinib. Avoid combination.Smith 2009, Tykerb August 2011

Lomitapide: CYP3A4 inhibitors (moderate) may increase the serum concentration of lomitapide. Avoid combination.Juxtapid December 2012

Lurasidone: CYP3A4 inhibitors (moderate) may increase the serum concentration of lurasidone. Consider therapy modification.Latuda June 2012, Latuda December 2012

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

Montelukast: Grapefruit juice may increase the serum concentration of montelukast. Avoid combination.Cingi 2013

Nicardipine: Grapefruit juice may increase the serum concentration of nicardipine. Monitor therapy.Bruggemann 1998, Ohnishi 2006, Uesawa 2008

Nifedipine: Grapefruit juice may increase the serum concentration of nifedipine. Avoid combination.Adigun 2002, Grundy 1998, Lown 1997, Miniscalco 1992, Odou 2005, Ohnishi 2006, Pisarik 1996, Procardia March 2006, Rashid 1993, Rashid 1995, Sigusch 1994, Uesawa 2008

Nimodipine: Grapefruit juice may increase the serum concentration of nimodipine. Avoid combination.Bruggemann 1998, Nimotop February 2008, Ohnishi 2006, Uesawa 2008

Nisoldipine: Grapefruit juice may increase the serum concentration of nisoldipine. Avoid combination.Bailey 1993, Ohnishi 2006, Sular January 2008, Takanaga 2000, Uesawa 2008

Nitrendipine: Grapefruit juice may increase the serum concentration of nitrendipine. Monitor therapy.Ohnishi 2006, Soons 1991, Uesawa 2008

Oxycodone (oral): Grapefruit juice may increase the serum concentration and half-life of oxycodone (oral). Monitor therapy.Feng 2017

P-gp/ABCB1 substrates: P-gp/ABCB1 inhibitors may increase the serum concentration of P-gp/ABCB1 substrates. P-gp inhibitors may also enhance the distribution of P-gp substrates to specific cells/tissues/organs where P-gp is present in large amounts (eg, brain, T-lymphocytes, testes). Monitor therapy.Albermann 2005, Callagan 2008, Gurley 2008, Ho 2005, Kim 2002, Kivisto 2004, Leslie 2005, Teng 2008, Wakasugi 1998

Pazopanib: Grapefruit juice may increase the serum concentration of pazopanib. Avoid combination.Votrient October 2009

Pimozide: Grapefruit juice may increase the serum concentration of pimozide. Avoid combination.Desta 1998, Desta 1999, Flockhart 1996, Orap August 2011

Pirfenidone: CYP1A2 inhibitors may increase the serum concentration of pirfenidone. Avoid combination.Esbriet October 2017 Grapefruit juice may decrease serum concentrations of pirfenidone during a fasted state, as demonstrated in persons of Han Chinese descent.Hu 2016

Pomalidomide: P-gp/ABCB1 inhibitors may increase the serum concentration of pomalidomide. Avoid combination.Pomalyst February 2013

Ponatinib: Grapefruit juice may increase the serum concentration of ponatinib. Consider therapy modification.Iclusig December 2012

Prasugrel: Grapefruit juice may decrease the serum concentration of the active metabolite of prasugrel. Platelet inhibition may be affected. Monitor closely.Holmberg 2015

Propafenone: CYP3A4 inhibitors (moderate) may increase the serum concentration of propafenone. Monitor therapy.Rythmol SR November 2011

Prucalopride: P-gp/ABCB1 inhibitors may increase the serum concentration of prucalopride. Monitor therapy.Resotran December 2011

Ranolazine: CYP3A4 inhibitors (moderate) may increase the serum concentration of ranolazine. Consider therapy modification.Bjornsson 2003, Jerling 2005, Ranexa November 2008

Regorafenib: Grapefruit juice may increase the serum concentration of regorafenib. Avoid combination.Stivarga September 2012

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.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

Silodosin: P-gp/ABCB1 inhibitors may increase the serum concentration of silodosin. Avoid combination.Rapaflo September 2008

Sirolimus: Grapefruit juice may increase the serum concentration of sirolimus. Monitor closely when used strategically as adjunctive therapy.Cohen 2012

Sunitinib: Grapefruit juice may increase the serum concentration of sunitinib. Monitor closely.van Erp 2011

Tacrolimus (systemic): Grapefruit juice may decrease the metabolism of tacrolimus (systemic). Monitor closely when used strategically as adjunctive therapy.Fukatsu 2006, Liu 2009, Peynaud 2007, Prograf February 2012, Tsuji 2016

Tacrolimus (topical): Grapefruit juice may decrease the metabolism of tacrolimus (topical). Monitor therapy.Alaiti 1998, Allen 2001, Allen 2002, Beyerler 2006, Conrotto 2006, Draelos 2005, Ghislain 2004, Harper 2005, Kameda 2003, Kawashima 1996, Krueger 2007, Pitarch 2006, Protopic January 2009, Prot-Labarthe 2007, Rubins 2005, Russel 2001, Teshima 2003, Undre 2009

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.Samsca May 2009

Topotecan: P-gp/ABCB1 inhibitors may increase the serum concentration of topotecan. Avoid combination.Chen 1991, Hendricks 1992, Hycamtin October 2007, Jonker 2000, Kruijtzer 2002, Leggas 2004, Maliepaard 1999, Maliepaard 2001

Toremifene: Grapefruit juice may increase the serum concentration of toremifene. Avoid combination.Fareston March 2011

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.Viibryd January 2011

Vincristine (liposomal): P-gp/ABCB1 inhibitors may increase the serum concentration of vincristine (liposomal). Avoid combination.Marqibo August 2012

Zuclopenthixol: CYP3A4 inhibitors (moderate) may increase the serum concentration of zuclopenthixol. Monitor therapy.Clopixol January 2011, Davies 2010

Medications for heart failure

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

Other interaction data

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

Adverse Reactions

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 15.5% (n=130) of hepatotoxicity cases were caused by herbals and dietary supplements, whereas 85% (n=709) were related to medications. Of the 130 cases of liver injury related to supplements, 65% were from nonbodybuilding supplements and occurred most often in Hispanic/Latino populations compared with non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent in cases of toxicity from nonbodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher with supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, grapefruit was among the 22% (n=116) labeled as single-ingredient products.Navarro 2014

Toxicology

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

References

Abbas R, Hug BA, Leister C, Burns J, Sonnichsen D. Effect of ketoconazole on the pharmacokinetics of oral bosutinib in healthy subjects. J Clin Pharmacol. 2011;51(12):1721-1727.21148045
Abilify (amiodarone) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; February 2011.
Adigun AQ, Mudasiru Z. Clinical effects of grapefruit juice-nifedipine interaction in a 54-year-old Nigerian: a case report. J Natl Med Assoc. 2002;94(4):276-278.11991343
Afinitor (everolimus) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; October 2010.
Akdag I, Ersoy A, Kahvecioglu S, Gullulu M, Dilek K. Acute colchicine intoxication during clarithromycin administration in patients with chronic renal failure. J Nephrol. 2006;19(4):515-517.17048210
Alaiti S, Kang S, Fiedler C, et al. Tacrolimus (FK506) ointment for atopic dermatitis: a phase I study in adults and children. J Am Acad Dermatol. 1998;38(1)69-76.9448208
Albermann N, Schmitz-Winnenthal FH, Z'graggen K, et al. Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2, BCRP/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver. Biochem Pharmacol. 2005;70(6):949-958.16054595
Allegra (fexofenadine hydrochloride) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis; July 2007.
Allen A, Siegfried E, Silverman R, et al. Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome. Arch Dermatol. 2001;137(6)747-750.11405764
Allen DM, Esterly NB. Significant systemic absorption of tacrolimus after topical application in a patient with lamellar ichthyosis. Arch Dermatol. 2002;138(9):1259-1260.12225004
Ando H, Tsuruoka S, Yanagihara H, et al. Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin. Br J Clin Pharmacol. 2005;60(5):494-497.16236039
Aung GL, O'Brien JG, Tien PG, et al. Increased aripiprazole concentrations in an HIV-positive male concurrently taking duloxetine, darunavir, and ritonavir. Ann Pharmacother. 2010;44(11):1850-1854.20978219
Azuma J, Hasunuma T, Kubo M, et al. The relationship between clinical pharmacokinetics of aripiprazole and CYP2D6 genetic polymorphism: effects of CYP enzyme inhibition by coadministration of paroxetine or fluvoxamine. Eur J Clin Pharmacol. 2012;68(1):29-37.21739267
Bailey DG, Spence JD, Munoz C, Arnold JM. Interaction of citrus juices with felodipine and nifedipine. Lancet. 1991;337(8736):268-269.1671113
Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD. Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin Pharmacol Ther. 1993;54(6):589-594.8275614
Bailey DG, Arnold JM, Munoz C, Spence JD. Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. Clin Pharmacol Ther. 1993;53(6):637-642.8513655
Bailey DG, Arnold JM, Bend JR, Tran LT, Spence JD. Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. Br J Clin Pharmacol. 1995;40(2):135-140.8562295
Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD. Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice. Clin Pharmacol Ther. 1996;60(1):25-33.8689808
Bailey DG, Dresser GK, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit-felodipine interaction: effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther. 2000;68(5):468-477.11103749
Bailey DG, Dresser GK, Bend JR. Bergamottin, lime juice, and red wine as inhibitors of cytochrome p450 3a4 activity: comparison with grapefruit juice. Clin Pharmacol Ther. 2003;73(6):529-537.12811362
Bailey DG, Dresser GK, Leake BF, Kim RB. Naringin is a major and selective clinical inhibitor of organic anion-transporting polypeptide 1A2 (OATP1A2) in grapefruit juice. Clin Pharmacol Ther. 2007;81(4):495-502.17301733
Baune B, Flinois JP, Furlan V, et al. Halofantrine metabolism in microsomes in man: major role of CYP 3A4 and CYP 3A5. J Pharm Pharmacol. 1999;51(4):419-426.10385214
Baune B, Furlan V, Taburet AM, et al. Effect of selected antimalarial drugs and inhibitors of cytochrome P-450 3A4 on halofantrine metabolism by human liver microsomes. Drug Metab Dispos. 1999;27(5):565-568.10220483
Beyerler M, Schmid-Grendelmeier P, Hafner J. Significantly elevated systemic levels after occlusive application of topical tacrolimus in atopic dermatitis. Dermatology. 2006;212(3):260-261.16549924
Bistrup C, Nielsen FT, Jeppesen UE, Dieperink H. Effect of grapefruit juice on Sandimmune Neoral absorption among stable renal allograft recipients. Nephrol Dial Transplant. 2001;16(2):373-377.11158415
Bjornsson TD, Callaghan JT, Einolf HJ, et al; Pharmaceutical Research and Manufacturers of America Drug Metabolism/Clinical Pharmacology Technical Working Groups. The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective. J Clin Pharmacol. 2003;43(5):443-469.12751267
Bonin B, Vandel P, Vandel S, Kantelip JP. Effect of grapefruit intake on carbamazepine bioavailability: a case report. Therapie. 2001;56(1):69-71.11322025
Bosulif (bosutinib) [prescribing information]. New York, NY: Pfizer; September 2012.
Bower S, Hull CJ. Comparative pharmacokinetics of fentanyl and alfentanil. Br J Anaesth. 1982;54(8):871-877.6125162
Bruggemann A, Blume H, Muck W, et al. Grapefruit juice increases oral nimodipine bioavailability. Int J Clin Pharmacol Ther. 1998;36(3):126-132.
Brunner LJ, Pai KS, Munar MY, Lande MB, Olyaei AJ, Mowry JA. Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients. Pediatr Transplant. 2000;4(4):313-321.11079273
Brunner LJ, Munar MY, Vallian J, et al. Interaction between cyclosporine and grapefruit juice requires long-term ingestion in stable renal transplant recipients. Pharmacotherapy. 1998;18(1):23-29.9469677
Butterweck V, Zdrojewski I, Galloway C, Frye R, Derendorf H. Toxicological and pharmacokinetic evaluation of concomitant intake of grapefruit juice and simvastatin in rats after repeated treatment over 28 days. Planta Med. 2009;75(11):1196-1202.19350484
Callaghan R, Crowley E, Potter S, et al. P-glycoprotein: so many ways to turn it on. J Clin Pharmacol. 2008;48(3):365-378.18156365
Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E. Acute colchicine intoxication - possible role of erythromycin administration. J Rheumatol.1992;19(3):494-496.1578471
Carper J. Grapefruit. In: The Food Pharmacy: Dramatic New Evidence That Food is Your Best Medicine. New York, NY: Bantam Books; 1988:213-215.
Chen AY, Yu C, Potmesil M, Wall ME, Wani MC, Liu LF. Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells. Cancer Res. 1991;51(22):6039-6044.1682041
Cheng VC, Ho PL,Yuen KY. Two probable cases of serious drug interaction between clarithromycin and colchicine. South Med J. 2005;98(8):811-813.16144178
Christensen H, Asberg A, Holmboe AB, Berg KJ. Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers. Eur J Clin Pharmacol. 2002;58(8):515-520.12451428
Cingi C, Toros SZ, Gürbüz MK, et al. Effect of grapefruit juice on bioavailability of montelukast. Laryngoscope. 2013;123(4):816-819.22951980
Citrus xparadisi Macfad. USDA, NRCS. 2018. The PLANTS Database. (http://plants.usda.gov, 27 May 2018). National Plant Data Team, Greensboro, NC 27401-4901 USA.
Clopixol (zuclopenthixol) [product monograph]. Montreal, Quebec: Lundbeck Canada; January 2011.
Coartem (artemether/lumefantrine) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; April 2009.
Cohen EE, Wu K, Hartford C, et al. Phase I studies of sirolimus alone or in combination with pharmacokinetic modulators in advanced cancer patients. Clin Cancer Res. 2012;18(17):4785-4793.22872575
Colcrys (colchicine) [prescribing information]. Philadelphia, PA: AR Scientific; July 2009.
Cometriq (cabozantinib) [prescribing information]. San Francisco, CA: Exelixis; December 2012.
Conrotto D, Carrozzo M, Ubertalli AV, et al. Dramatic increase of tacrolimus plasma concentration during topical treatment for oral graft-versus-host disease. Transplantation. 2006;82(8):1113-1115.17060865
Cordarone (amiodarone) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals; December 2008.
Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB. OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999;277(8):866-871.10421612
Davidson A, Knox C. Grapefruit, pomelo, ugli. In: Fruit: A Connoiseur's Guide and Cookbook. New York, NY: Simon and Schuster; 1991:66.
Davies SJ, Westin AA, Castberg I, et al. Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies. Acta Psychiatr Scand. 2010;122(6):444-453.20946203
Desta Z, Kerbusch T, Soukhova N, Richard E, Ko JW, Flockhart DA. Identification and characterization of human cytochrome P450 isoforms interacting with pimozide. J Pharmacol Exp Ther. 1998; 285(2):428-437.9580580
Desta Z, Kerbusch T, Flockhart DA. Effect of clarithromycin on the pharmacokinetics and pharmacodynamics of pimozide in healthy, poor, and extensive metabolizers of cytochrome P450 2D6 (CYP2D6). Clin Pharmacol Ther. 1999;65(1):10-20.9951426
Desta Z, Kivisto KT, Lilja JJ, et al. Stereoselective pharmacokinetics of cisapride in healthy volunteers and the effect of repeated administration of grapefruit juice. Br J Clin Pharmacol. 2001;52(4):399-407.11678783
de Vries R, Smit JW, Hellemans P, et al. Stable isotope-labelled intravenous microdose for absolute bioavailability and effect of grapefruit juice on ibrutinib in healthy adults. Br J Clin Pharmacol. 2016;81(2):235-245.26382728
Dogukan A, Oymak FS, Taskapan H, Güven M, Tokgoz B, Utas C. Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (capd). possible role of clarithromycin administration. Clin Nephrol. 2001;55(2):181-182.11269688
Draelos Z, Nayak A, Pariser D, et al. Pharmacokinetics of topical calcineurin inhibitors in adult atopic dermatitis: a randomized, investigator-blind comparison. J Am Acad Dermatol. 2005;53(4):602-609.16198779
Dresser GK, Bailey DG,Carruthers SG. Grapefruit juice--felodipine interaction in the elderly. Clin Pharmacol Ther. 2000;68(1):28-34.10945313
Dresser GK, Bailey DG, Leake BF, et al. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther. 2002,71(1):11-20.11823753
Ducharme MP, Provenzano R, Dehoorne-Smith M, Edwards DJ. Trough concentrations of cyclosporine in blood following administration with grapefruit juice. Br J Clin Pharm. 1993;36(5):457-459.12959294
Ducharme MP, Warbasse LH, Edwards DJ. Disposition of intravenous and oral cyclosporine after administration with grapefruit juice. Clin Pharmacol Ther. 1995;57(5):485-491.7768070
Dupont P, Hunt I, Goldberg L, Warrens A. Colchicine myoneuropathy in a renal transplant patient. Transpl Int. 2002;15(7):374-376.12122515
Edgar B, Bailey D, Bergstrand R, Johnsson G, Regårdh CG. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance. Eur J Clin Pharmacol. 1992;42(3):313-317.1577050
Edwards DJ, Ducharme MP, Provenzano R, et al. Effect of grapefruit juice on blood concentrations of cyclosporine. Clin Pharmacol Ther. 1993;53:237.
Edwards D, Bellevue FH 3rd, Woster PM. Identification of 6',7' -dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug Metab Dispos. 1996;24(12):1287-1290.8971132
Edwards DJ, Woster PM, and Warbasse LH. Effect of grapefruit juice and seville orange juice on cyclosporine disposition. Clin Pharmacol Ther. 1998;63:149.
Eleftheriou G, Bacis G, Fiocchi R, Sebastiano R. Colchicine-induced toxicity in a heart transplant patient with chronic renal failure. Clin Toxicol (Phila). 2008;46(9):827-830.18608282
El-Lakkany NM, Seif el-Din SH, Badawy AA, et al. Effect of artemether alone and in combination with grapefruit juice on hepatic drug-metabolising enzymes and biochemical aspects in experimental schistosoma mansoni. Int J Parasitol. 2004;34(12):1405-1412.15542101
Ensminger ME, Ensminger AH. Grapefruit. In: Foods & Nutrition Encyclopedia. Vol 1. 2nd ed. Boca Raton, FL: CRC Press; 1993:1097-1099.
Entocort EC (budesonide) systemic [prescribing information]. San Diego, CA: Prometheus Laboratories; June 2009.
Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235.11950176
Esbriet (pirfenidone) [prescribing information]. South San Francisco, California: Genentech; October 2017.
Fareston (toremifene) [prescribing information]. Memphis, TN: GTx Inc; March 2011.
Feng XQ, Zhu LL, Zhou Q. Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management. J Pain Res. 2017;10:1225-1239.28579821
Ferdman RM, Ong PY, Church JA. Pectin anaphylaxis and possible association with cashew allergy. Ann Allergy Asthma Immunol. 2006;97(6):759-760.17201234
Flockhart DA, Richard E, Woosely RL, et al. A metabolic interaction between clarithromycin and pimozide may result in cardiac toxicity. Clin Pharmacol Ther. 1996;59:189.
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(1):45-53.11956673
Fujioka K, Greenway F, Sheard J, Ying Y. The effects of grapefruit on weight and insulin resistance: relationship to the metabolic syndrome. J Med Food. 2006;9(1):49-54.16579728
Fukatsu S, Fukudo M, Masuda S, et al. Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient. Drug Metab Pharmacokinet. 2006;21(2):122-125.16702731
Fukazawa I, Uchida N, Uchida E, Yasuhara H. Effects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in japanese. Br J Clin Pharmacol. 2004;57(4):448-455.15025743
Garg SK, Kumar N, Bhargava VK, Prabhakar SK. Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy. Clin Pharmacol Ther. 1998;64(3):286-288.9757152
Ghislain PD, De Decker I, Lachapelle JM. Efficacy and systemic absorption of topical tacrolimus used in pyoderma gangrenosum. Br J Dermatol. 2004;150(5):1052-1053.15149540
Giamperi L, Fraternale D, Bucchini A, Ricci D. Antioxidant activity of Citrus paradisi seeds glyceric extract. Fitoterapia. 2004;75(2):221-224.17215845
Glaeser H, Bailey DG, Dresser GK, et al. Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharmacol Ther. 2007;81(3):362-370.15030930
Goldfarb DS, Asplin JR. Effect of grapefruit juice on urinary lithogenicity. J Urol. 2001;166(1):263-267.11435883
Goosen TC, Cillie D, Bailey DG, et al. Bergamottin contribution to the grapefruit juice-felodipine interaction and disposition in humans. Clin Pharmacol Ther. 2004;76(6):607-617.15592332
Gorinstein S, Caspi A, Libman I, Katrich E, Lerner HT, Trakhtenberg S. Fresh israeli jaffa sweetie juice consumption improves lipid metabolism and increases antioxidant capacity in hypercholesterolemic patients suffering from coronary artery disease: studies in vitro and in humans and positive changes in albumin and fibrinogen fractions. J Agric Food Chem. 2004;52(16):5215-5222.15291499
Gorinstein S, Caspi A, Libman I, et al. Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. J Agric Food Chem. 2006;54(5):1887-1892.16506849
Grande LA, Mendez RD, Krug RT, Verschuyl EJ. Attention—grapefruit! Lancet. 2009;373(9670):1222.19345832
Gross AS, Goh YD, Addison RS, Shenfield GM. Influence of grapefruit juice on cisapride pharmacokinetics. Clin Pharmacol Ther. 1999;65(4):395-401.10223776
Gruberg L, Har-Zahav Y, Agranat O, Freimark D. Acute myopathy induced by colchicine in a cyclosporine treated heart transplant recipient: possible role of the multidrug resistance transporter. Transplant Proc. 1999;31(5):2157-2158.10455999
Grundy JS, Eliot LA, Kulmatycki KM, Foster RT. Grapefruit juice and orange juice effects on the bioavailability of nifedipine in the rat. Biopharm Drug Dispos. 1998;19(3):175-183.9570001
Gubbins PO, McConnell SA, Gurley BJ, et al. Influence of grapefruit juice on the systemic availability of itraconazole oral solution in healthy adult volunteers. Pharmacotherapy. 2004;24(4):460-467.15098799
Gubbins PO, Gurley BJ, Williams DK, et al. Examining sex-related differences in enteric itraconazole metabolism in healthy adults using grapefruit juice. Eur J Clin Pharmacol. 2008;64(3):293-301.18172627
Gurley BJ, Swain A, Williams DK, et al. Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. Mol Nutr Food Res. 2008;52(7):772-779.18214850
Habauzit V, Verny MA, Milenkovic D, et al. Flavanones protect from arterial stiffness in postmenopausal women consuming grapefruit juice for 6 mo: a randomized, controlled, crossover trial. Am J Clin Nutr. 2015;102(1):66-74.26016866
Halfan (halofantrine) [prescribing information]. Philadelphia, PA: SmithKline Beecham Pharmaceuticals; October 2001.
Hallberg P, Marten L, Wadelius M. Possible fluconazole-fentanyl interaction-a case report. Eur J Clin Pharmacol. 2006;62(6):491-492.16758267
Halliday RC, Jones BC, Smith DA, Kitteringham NR, Park BK. An investigation of the interaction between halofantrine, CYP2D6 and CYP3A4: studies with human liver microsomes and heterologous enzyme expression systems. Br J Clin Pharmacol. 1995;40(4):369-378.8554939
Harper J, Smith C, Rubins A, et al. A multicenter study of the pharmacokinetics of tacrolimus ointment after first and repeated application to children with atopic dermatitis. J Invest Dermatol. 2005;124(4):695-699.15816825
Heggers JP, Cottingham J, Gusman J, et al. The effectiveness of processed grapefruit-seed extract as an antibacterial agent: II. Mechanism of action and in vitro toxicity. J Altern Complement Med. 2002;8(3):333-340.12165191
Hendricks CB, Rowinsky EK, Grochow LB, Donehower RC, Kaufmann SH. Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Cancer Res. 1992;52(8):2268-22678.1348448
Hermann M, Asberg A, Reubsaet JL, Sather S, Berg KJ, Christensen H. Intake of grapefruit juice alters the metabolic pattern of cyclosporine a in renal transplant recipients. Int J Clin Pharmacol Ther. 2002;40(10):451-456.12395977
Ho PC, Ghose K, Saville D, et al. Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers. Eur J Clin Pharmacol. 2000;56(9-6):693-698.11214778
Ho RH, Kim RB. Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ther. 2005;78(3):260-277.16153397
Hollander AA, van Rooij J, Lentjes GW, et al. The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients. Clin Pharmacol Ther. 1995;57(3):318-324.7697949
Holmberg MT, Tornio A, Joutsi-Korhonen L, et al. Grapefruit juice markedly increases the plasma concentrations and antiplatelet effects of ticagrelor in healthy subjects. Br J Clin Pharmacol. 2013;75(6):1488-1496.23126367
Holmberg MT, Tornio A, Neuvonen M, Neuvonen PJ, Backman JT, Niemi M. Grapefruit juice inhibits the metabolic activation of clopidogrel. Clin Pharmacol Ther. 2014;95(3):307-313.24067745
Holmberg MT, Tornio A, Hyvärinen H, et al. Effect of grapefruit juice on the bioactivation of prasugrel. Br J Clin Pharmacol. 2015;80(1):139-145.25557052
Holtzman CW, Wiggins BS, Spinler SA. Role of P-glycoprotein in statin drug interactions. Pharmacotherapy. 2006;26(11):1601-1607.17064205
Hönow R, Laube N, Schneider A, Kessler T, Hesse A. Influence of grapefruit-, orange- and apple-juice consumption on urinary variables and risk of crystallization. Br J Nutr. 2003;90(2):295-300.12908889
Hori H, Yoshimura R, Ueda N, et al. Grapefruit juice-fluvoxamine interaction--is it risky or not? J Clin Psychopharmacol. 2003;23(4):422-424.12920426
Hu J, Shang D, Xu X, He X, Ni X, Zhang M, Wang Z, Qiu C, Deng S, Lu H, Zhu X, Huang W, Wen Y. Effect of grapefruit juice and food on the pharmacokinetics of pirfenidone in healthy Chinese volunteers: a diet-drug interaction study. Xenobiotica. 2016;46(6):516-521.26407124
Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ. Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice. Clin Pharmacol Ther. 1995;58(2):127-131.7648762
Hung IF, Wu AK, Cheng VC, et al. Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study. Clin Infect Dis. 2005;41(3):291-300.16007523
Hycamtin (topotecan) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; October 2007.
Ibrahim AE, Feldman J, Karim A, et al. Simultaneous assessment of drug interactions with low- and high-extraction opioids: application to parecoxib effects on the pharmacokinetics and pharmacodynamics of fentanyl and alfentanil. Anesthesiology. 2003;98(4):853-861.12657846
Iclusig (ponatinib) [prescribing information]. Cambridge, MA: Ariad Pharmaceuticals; December 2012.
Ifex (ifosfamide) [prescribing information]. Deerfield, IL: Baxter Healthcare; March 2012.
Inlyta (axitinib) [prescribing information]. New York, NY: Pfizer; January 2012.
Inspra (eplerenone) [prescribing information]. New York, NY: Pfizer; June 2012.
Inspra [prescribing information]. Kirkland, Quebec; August 2012.
Ioannides-Demos LL, Christophidis N, Ryan P, Angelis P, Liolios L, McLean AJ. Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases. J Rheumatol. 1997;24(1):49-54.9002010
Drug interaction incident with HIV post-exposure prophylaxis. ISMP Canada Safety Bulletin. 2008;8(3):1-2. http://www.ismp-canada.org/download/ISMPCSB2008-03HIVPEP.pdf. Accessed December 2, 2008.
Jakafi (ruxolitinib) [prescribing information]. Wilmington, DE: Incyte; November 2011.
Jerling M, Huan BL, Leung K, Chu N, Abdallah H, Hussein Z. Studies to investigate the pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem, or simvastatin during combined administration in healthy subjects. J Clin Pharmacol. 2005;45(4):422-433.15778423
Jonker JW, Smit JW, Brinkhuis RF, et al. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst. 2000;92(20):1651-1656.1348448
Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol. 1996;51(2):189-193.8911887
Josefsson M, Ahlner J. Amlodipine and grapefruit juice. Br J Clin Pharmacol. 2002;53(4):405; author reply 6.11966676
Juxtapid (lomitapide) [prescribing information]. Cambridge, MA: Aegerion Pharmaceuticals; December 2012.
Kakar SM, Paine MF, Stewart PW, Watkins PB. 6'7'-Dihydroxybergamottin contributes to the grapefruit juice effect. Clin Pharmacol Ther. 2004;75(6):569-579.15179411
Kalydeco (ivacaftor) [prescribing information]. Cambridge, MA: Vertex Pharmaceuticals Incorporated; January 2012.
Kameda G, Kramm C Niehues T, Hermsen D, Krutmann J, Niehues T. Unexpected high serum levels of tacrolimus after a single topical application in an infant. J Pediatr. 2003;143(4):462.12970650
Kantola T, Kivistö KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatic acid. Clin Pharmacol Ther. 1998;63(4):397-402.9585793
Kawaguchi-Suzuki M, Nasiri-Kenari N, Shuster J, et al. Effect of low-furanocoumarin hybrid grapefruit juice consumption on midazolam pharmacokinetics. J Clin Pharmacol. 2017;57(3):305-311.27503364
Kawakami M, Suzuki K, Ishizuka T, et al. Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects. Int J Clin Pharmacol Ther. 1998;36(6):306-308.9660036
Kawashima M, Nakagawaw H, Ohtsuki M, Tamaki K, Ishibashi Y. Tacrolimus concentrations in blood during topical treatment of atopic dermatitis. Lancet. 1996;348(9036):1240-1241.8898050
Kerbusch T, Jansen RL, Mathot RA, et al. Modulation of the cytochrome P450-mediated metabolism of ifosfamide by ketoconazole and rifampin. Clin Pharmacol Ther. 2001;70(2):132-141.11503007
Khoo SM, Porter JH, Edwards GA, Charman WN. Metabolism of halofantrine to its equipotent metabolite, desbutylhalofantrine, is decreased when orally administered with ketoconazole. J Pharm Sci. 1998;87(12):1538-1541.10189263
Kim RB. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev. 2002;34(1-2):47-54.11996011
Kim EH, Hankinson SE, Eliassen AH, Willett WC. A prospective study of grapefruit and grapefruit juice intake and breast cancer risk. Br J Cancer. 2008;98(1):240-241.18026192
Kivisto KT, Lilja JJ, Backman JT, Neuvonen PJ. Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride. Clin Pharmacol Ther. 1999;66(5):448-453.10579471
Kivisto KT, Niemi M, Fromm MF. Functional interaction of intestinal CYP3A4 and P-glycoprotein. Fundam Clin Pharmacol. 2004;18(6):621-626.15548232
Krueger GG, Eichenfield L, Goodman JJ, et al. Pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adult and pediatric patients with moderate to severe atopic dermatitis. J Drugs Dermatol. 2007;6(2):185-193.17373177
Kruijtzer CMF, Beijnen JH, Rosing H, et al. Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and p-glycoprotein inhibitor GF120918. J Clin Oncol. 2002;20(13):2943-2950.12089223
Ku YM, Min KE, Flanigan MJ. The effect of grapefruit juice on microemulsion cyclosporine (Neoral) pharmacokinetics in healthy volunteers. Pharmacotherapy. 1998;18:442.
Kubitza D, Mueck W, Becka M. No interaction between rivaroxaban - a novel, oral, direct factor Xa inhibitor - and atorvastatin [abstract PO62]. Pathophysiol Haemost Thromb. 2008;36(suppl 1):A40.
Kubo M, Koue T, Inaba A, et al. Influence of itraconazole co-administration and CYP2D6 genotype on the pharmacokinetics of the new antipsychotic aripiprazole. Drug Metab Pharmacokinet. 2005;20(1):55-64.15770075
Kupferschmidt HH, Ha RH, Ziegler WH, et al. Interaction between grapefruit juice and midazolam in humans. Clin Pharmacol Ther. 1995;58(1):20-28.7628179
Latuda (lurasidone) [product monograph]. Mississauga, Ontario: Sunovion Pharmaceuticals Canada; June 2012.
Latuda (lurasidone) [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals; December 2012.
Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BC. The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Clin Ther. 1999;21(11):1890-1899.10890261
Lee M, Min DI, Ku YM, Flanigan M.. Effect of grapefruit juice on pharmacokinetics of microemulsion cyclosporine in African American subjects compared with Caucasian subjects: does ethnic difference matter? J Clin Pharmacol. 2001;41(3):317-323.11269572
Leggas M, Adachi M, Scheffer GL, et al. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol Cell Biol. 2004;24(17):7612-7621.15314169
Leslie EM, Deeley RG, Cole SP. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol. 2005;204(3):216-237.15845415
Libersa CC, Brique SA, Motte KB, et al. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br J Clin Pharmacol. 2000;49(4):373-378.10759694
Lilja JJ, Kivisto KT, Backman JT, Lamberg TS, Neuvonen PJ. Grapefruit juice substantially increases plasma concentrations of buspirone. Clin Pharmacol Ther. 1998;64(6):655-660.9871430
Lilja JJ, Kivistö 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(5):477-483.9834039
Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther. 1999;66(2):118-127.10460065
Lilja JJ, Kivistö KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther. 2000;68(4):384-390.11061578
Lilja JJ, Neuvonen M, Neuvonen PJ. Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol. 2004;58(1):56-60.15206993
Lipitor (atorvastatin) [prescribing information]. New York, NY: Pfizer; June 2009.
Liu C, Shang YF, Zhang XF, et al. Co-administration of grapefruit juice increases bioavailability of tacrolimus in liver transplant patients: a prospective study. Eur J Clin Pharmacol. 2009;65(9):881-885.19629461
Lown KS, Bailey DG, Fontana RJ, et al. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest. 1997;99(10):2545-25539153299
Lundahl J, Regardh CG, Edgar B, Johnsson G. Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur J Clin Pharmacol. 1995;49(1-2):61-67.8751023
Lundahl J, Regårdh CG, Edgar B, Johnsson G. Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur J Clin Pharmacol. 1997;52(2):139-145.9174684
Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther. 2001;69(1):14-23.11180034
Maliepaard M, van Gastelen MA, de Jong LA, et al. Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res. 1999;59(18):4559-4563.10493507
Maliepaard M, van Gastelen MA, Tohgo A, et al. Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res. 2001;7(4):935-941.11309344
Manchee GR, Eddershaw PJ, Ranshaw LE, et al. The aliphatic oxidation of salmeterol to alpha-hydroxysalmeterol in human liver microsomes is catalyzed by CYP3A. Drug Metab Dispos. 1996;24(5):555-559.8723736
Marqibo (vincristine) [prescribing information]. South San Francisco, CA: Talon Therapeutics; August 2012
McCune JS, Risler LJ, Phillips BR, Thummel KE, Blough D, Shen DD. Contribution of CYP3A5 to hepatic and renal ifosfamide N-dechloroethylation. Drug Metab Dispos. 2005;33(7):1074-1081.15821045
Mehrsai AR, Pourmand G, Mansour D, et al. Effect of grapefruit juice on serum concentration of cyclosporine in Iranian renal transplant patients. Transplant Proc. 2003;35(7):2739-2741.14612100
Menta R, Rossi E, Guariglia A, David S, Cambi V. Reversible acute cyclosporine nephrotoxicity induced by colchicine administration. Nephrol Dial Transplant. 1987;2(5):380-381.3122121
Mercadante S, Villari P, Ferrera P. Itraconazole-fentanyl interaction in a cancer patient. J Pain Symptom Manage. 2002;24(3):284-286.12458106
Methlie P, Husebye EE, Hustad S, Lien EA, Løvås K. Grapefruit juice and licorice increase cortisol availability in patients with Addison's disease. Eur J Endocrinol. 2011;165(5):761-769.21896619
Mevacor (lovastatin) [prescribing information]. Whitehouse Station, NJ: Merck & Co; May 2010.
Min DI, Ku YM, Perry PJ, et al. The effect of grapefruit juice on cyclosporine pharmacokinetics in renal allograft recipients. Pharmacotherapy. 1996;16:516.
Miniscalco A, Lundahl J, Regårdh CG, Edgar B, Eriksson UG. Inhibition of dihydropyridine metabolism in rat and human liver microsomes by flavonoids found in grapefruit juice. J Pharmacol Exp Ther. 1992;261(3):1195-1199.1602384
Misaka S, Miyazaki N, Yatabe MS, et al. Pharmacokinetic and pharmacodynamic interaction of nadolol with itraconazole, rifampicin and grapefruit juice in healthy volunteers. J Clin Pharmacol. 2013;53(7):738-745.23677858
Monroe KR, Murphy SP, Henderson BE, et al. Dietary fiber intake and endogenous serum hormone levels in naturally postmenopausal Mexican American women: the Multiethnic Cohort Study. Nutr Cancer. 2007;58(2):127-135.17640158
Multaq (dronedarone) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US; June 2009.
Muraki I, Imamura F, Manson JE, et al. Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies. BMJ. 2013;347:f5001.23990623
Nagy J, Schipper HG, Koopmans RP, et al. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg. 2002;66(3):260-263.12139218
Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. drug-induced liver injury network. Hepatology. 2014;60(4):1399-1408.25043597
Nimotop (nimodipine) [prescribing information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals; February 2008.
Noppen M, Velkiniers B, Dierckx R, Bruyland M, Vanhaelst L. Cyclosporine and myopathy. Ann Intern Med. 1987;107(6):945-946.3688695
Odou P, Ferrari N, Barthélémy C, et al. Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms. J Clin Pharm Ther. 2005;30(2):153-158.15811168
Oesterheld J, Kallepalli BR. Grapefruit juice and clomipramine: shifting metabolic ratios. J Clin Psychopharmacol. 1997;17(1):62-63.9004067
Offman EM, Freeman DJ, Dresser GK, Munoz C, Bend JR, Bailey DG. Red wine-cisapride interaction: comparison with grapefruit juice. Clin Pharmacol Ther. 2001;70(1):17-23.11452240
Ohnishi A, Ohtani H, Sawada Y. Major determinant factors of the extent of interaction between grapefruit juice and calcium channel antagonists. Br J Clin Pharmacol. 2006;62(2):196-199.16842394
Olkkola KT, Palkama VJ, Neuvonen PJ. Ritonavir's role in reducing fentanyl clearance and prolonging its half-life. Anesthesiology. 1999;91(3):681-685.10485779
Omar MA, Wilson JP, Cox TS. Rhabdomyolysis and HMG-CoA reductase inhibitors. Ann Pharmacother. 2001;35(9):1096-1107.11573861
Onakpoya I, O'Sullivan J, Heneghan C, Thompson M. The effect of grapefruits (Citrus paradisi) on body weight and cardiovascular risk factors: A systematic review and meta-analysis of randomized clinical trials. Crit Rev Food Sci Nutr. 2017;57(3):602-612.25880021
Onglyza (saxagliptin) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; July 2009.
Orap (pimozide) [prescribing information]. Sellersville, PA: Teva Pharmaceuticals USA; August 2011.
Oyelami OA, Agbakwuru EA, Adeyemi LA, Adedeji GB. The effectiveness of grapefruit (Citrus paradisi) seeds in treating urinary tract infections. J Altern Complement Med. 2005;11(2):369-371.15865506
Page RL 2nd, O'Bryant CL, Cheng D, et al; American Heart Association Clinical Pharmacology and Heart Failure and Transplantation Committees of the Council on Clinical Cardiology; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Drugs That May Cause or Exacerbate Heart Failure: A Scientific Statement From the American Heart Association. Circulation. 2016;134(6):e32-e69.27400984
Paine MF, Criss AB, Watkins PB. Two major grapefruit juice components differ in time to onset of intestinal CYP3A4 inhibition. J Pharmacol Exp Ther. 2005;312(3):1151-1160.15485894
Paine MF, Widmer WW, Hart HL, et al. A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction. Am J Clin Nutr. 2006;83(5):1097-1105.16685052
Palkama VJ, Neuvonen PJ, Olkkola KT. The CYP 3A4 inhibitor itraconazole has no effect on the pharmacokinetics of I.V. fentanyl. Br J Anaesth. 1998;81(4):598-600.9924238
Patel CG, Li L, Girgis S, Kornhauser DM, Frevert EU, Boulton DW. Two-way pharmacokinetic interaction studies between saxagliptin and cytochrome P450 substrates or inhibitors: simvastatin, diltiazem extended-release, and ketoconazole. Clin Pharmacol. 2011;3:13-25.22287853
Penzak SR, Gubbins PO, Gurley BJ, et al. Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers. Ther Drug Monit. 1999;21(3):304-309.10365642
Peynaud D, Charpiat B, Vial T, Gallavardin M, Ducerf C. Tacrolimus severe overdosage after intake of masked grapefruit in orange marmalade. Eur J Clin Pharmacol. 2007;63(7):721-722.17530235
Piccirillo G, Magrì D, Matera S, et al. Effects of pink grapefruit juice on QT variability in patients with dilated or hypertensive cardiomyopathy and in healthy subjects. Transl Res. 2008;151(5):267-272.18433709
Pisarik P. Blood pressure-lowering effect of adding grapefruit juice to nifedipine and terazosin in a patient with severe renovascular hypertension. Arch Fam Med. 1996;5(7):413-416.8665000
Pitarch G, Torrijos A, Mahiques L, et al. Systemic absorption of topical tacrolimus in pyoderma gangrenosum. Acta Derm Venereol. 2006;86(1)64-65.16585995
Pithavala YK, Tong W, Mount J, et al. Effect of ketoconazole on the pharmacokinetics of axitinib in healthy volunteers. Invest New Drugs. 2012;30(1):273-281.20740300
Plendil (felodipine) [product monograph]. Mississauga, Ontario: AstraZeneca Canada; June 2008.
Pomalyst (pomalidomide) [prescribing information]. Summit, NJ: Celgene Corporation; February 2013.
Pradax (dabigatran etexilate) [product monograph]. Burlington, Ontario, Canada: Boehringer Ingelheim Canada; January 2012.
Pradaxa (dabigatran etexilate) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals; November 2011.
Prezioso D, Strazzullo P, Lotti T, et al; CLU Working Group. Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group. Arch Ital Urol Androl. 2015;87(2):105-120.26150027
Procardia (nifedipine) [prescribing information]. New York, NY: Pfizer; March 2006.
Procoralan (ivabradine) [prescribing information]. Suresnes Cedex, France: Les Laboratoires Servier; August 2010.
Prograf (tacrolimus) [prescribing information]. Deerfield, IL: Astellas Pharma US; February 2012.
Proppe D, Visser K, Bartels R, et al. Grapefruit juice selectively modifies cyclosporine a metabolite patterns in renal transplant patients. Clin Pharmacol Ther. 1996;59:138.
Prot-Labarthe S, Therrien R, Champagne MA, Duval M, Joubert C. Toxic serum levels of tacrolimus after topical administration in an infant with severe cutaneous graft-versus-host disease. Bone Marrow Transplant. 2007;40(3):295-296.17549052
Protopic (tacrolimus) topical [prescribing information]. Deerfield, IL: Astellas Pharma US; January 2009.
Pulmicort (budesonide) oral inhalation [prescribing information]. Wilmington, DE: AstraZeneca LP; July 2010.
Rampersaud GC, Valim MF. 100% citrus juice: Nutritional contribution, dietary benefits, and association with anthropometric measures. Crit Rev Food SciNutr. 2017;57(1):129-140.25831042
Ranexa (ranolazine) [prescribing information]. Palo Alto, CA: CV Therapeutics; November 2008.
Rapaflo (silodosin) [prescribing information]. Corona, CA: Watson Pharmaceuticals; September 2008.
Rashid J, McKinstry C, Renwick AG, Dirnhuber M, Waller DG, George CF. Quercetin, an in vitro inhibitor of CYP3A, does not contribute to the interaction between nifedipine and grapefruit juice. Br J Clin Pharmacol. 1993;36(5):460-463.12959295
Rashid TJ, Martin U, Clarke H, Waller DG, Renwick AG, George CF. Factors affecting the absolute bioavailability of nifedipine. Br J Clin Pharmacol. 1995;40(1):51-58.8527268
Raucoules-Aimé M, Kaidomar M, Levron JC, et al. Hepatic disposition of alfentanil and sufentanil in patients undergoing orthotopic liver transplantation. Anesth Analg. 1997;84(5):1019-1024.9141924
Reshef N, Hayari Y, Goren C, Boaz M, Madar Z, Knobler H. Antihypertensive effect of sweetie fruit in patients with stage I hypertension. Am J Hypertens. 2005;18(10):1360-1363.16202862
Resotran (prucalopride) [product monograph]. Toronto, Ontario, Canada: Janssen; December 2011.
Rieger EH, Halasz NA, Wahlstrom HE. Colchicine neuromyopathy after renal transplantation. Transplantation. 1990;49(6):1196-1198.2360262
Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kélaïdi C, Blanche P. Acute colchicine intoxication during clarithromycin administration. Ann Pharmacother. 2004;38(12):2074-2077.15494379
Romaszko E, Marzec-Wróblewska U, Badura A, Buciński A. Does consumption of red grapefruit juice alter naringenin concentrations in milk produced by breastfeeding mothers? PLoS One. 2017;12(10):e0185954.28982188
Rubins A, Gutmane R, Valdmane N, Stevenson P, Foster C, Undre N. Pharmacokinetics of 0.1% tacrolimus ointment after first and repeated application to adults with moderate to severe atopic dermatitis. J Invest Dermatol. 2005;125(1):68-71.15982304
Rumpf KW, Henning HV. Is myopathy in renal transplant patients induced by cyclosporine or colchicine? Lancet. 1990;335(8692):800-801.1969550
Russel RK, Richardson N, Wilson DC. Systemic absorption with complications during topical tacrolimus treatment for orofacial Crohn disease. J Pediatr Gastroenterol Nutr. 2001;32(2):207-208.11321395
Rythmol SR (propafenone) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; November 2011.
Saari TI, Laine K, Neuvonen M, et al. Effect of voriconazole and fluconazole on the pharmacokinetics of intravenous fentanyl. Eur J Clin Pharmacol. 2008;64(1):25-30.17987285
Samsca (tolvaptan) [prescribing information]. Tokyo, Japan: Otsuka Pharmaceutical; May 2009.
Satoh H, Yamashita F, Tsujimoto M, et al. Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos. 2005;33(4):518-523.15640378
Schmiedlin-Ren P, Edwards DJ, Fitzsimmons ME, et al. Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab Dispos. 1997;25(11):1228-1233.9351897
Seden K, Dickinson L, Khoo S, Back D. Grapefruit-drug interactions. Drugs. 2010;70(18):2373-2407.21142260
Seidegard J, Randvall G, Nyberg L, Borgå O. Grapefruit juice interaction with oral budesonide: equal effect on immediate-release and delayed-release formulations. Pharmazie. 2009;64(7):461-465.19694184
Serevent (salmeterol) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; March 2008.
Shi JG, Chen X, Emm T, et al. The effect of CYP3A4 inhibition or induction on the pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424 Phosphate) in healthy volunteers. J Clin Pharmacol. 2012;52(6):809-818.21602517
Sigusch H, Henschel L, Kraul H, Merkel U, Hoffmann A. Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects. Pharmazie. 1994;49(9):675-679.7972311
Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A. Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation. Pharmazie. 1994;49(7):522-524.8073064
Smith DA, Koch KM, Arya N, Bowen CJ, Herendeen JM, Beelen A. Effects of ketoconazole and carbamazepine on lapatinib pharmacokinetics in healthy subjects. Br J Clin Pharmacol. 2009;67(4):421-426.19371315
Soons PA, Vogels BA, Roosemalen MC, et al. Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans. Clin Pharmacol Ther. 1991;50(4):394-403.1914375
Spencer EA, Key TJ, Appleby PN, et al. Prospective study of the association between grapefruit intake and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control. 2009;20(6):803-809.19224379
Staudte H, Sigusch BW, Glockmann E. Grapefruit consumption improves vitamin C status in periodontitis patients. Br Dent J. 2005;199(4):213-217.16127404
Stendra (avanafil) [prescribing information]. Mountain View, CA: Vivus; April 2012.
Stivarga (regorafenib) [prescribing information]. Wayne, NJ: Bayer HealthCare Pharmaceuticals; September 2012.
Sular (nisoldipine) [prescribing information]. Atlanta, GA: Sciele Pharma; January 2008.
Sun J. D-Limonene: safety and clinical applications. Altern Med Rev. 2007;12(3):259-264.18072821
Takanaga H, Ohnishi A, Murakami H, et al. Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. Clin Pharmacol Ther. 2000;67(3):201-214.10741622
Tapaninen T, Neuvonen PJ, Niemi M. Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren. Clin Pharmacol Ther. 2010;88(3):339-342.20664534
Tekturna (aliskiren) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; August 2010.
Teng S, Piquette-Miller M. Regulation of transporters by nuclear hormone receptors: implications during inflammation. Mol Pharm. 2008;5(1):67-76.18072749
Teshima D, Ikesue H, Itoh Y, Urabe K, Furue M, Oishi R. Increased topical tacrolimus absorption in generalized leukemic erythroderma. Ann Pharmacother. 2003;37(10):1444-1447.14519034
Trinchieri A, Lizzano R, Bernardini P, et al. Effect of acute load of grapefruit juice on urinary excretion of citrate and urinary risk factors for renal stone formation. Dig Liver Dis. 2002;34(suppl 2):S160-S163.12408462
Troger U, Lins H, Scherrmann JM, Wallesch CW, Bode-Böger SM. Tetraparesis associated with colchicine is probably due to inhibition by verapamil of the p-glycoprotein efflux pump in the blood-brain barrier. BMJ. 2005;331(7517):613.16148013
Tsuji H, Ohmura K, Nakashima R, et al. Efficacy and safety of grapefruit juice intake accompanying tacrolimus treatment in connective tissue disease patients. Intern Med. 2016;55(12):1547-1552.27301503
Tykerb (lapatinib) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; August 2011.
Ueda N, Yoshimura R, Umene-Nakano W, Kornhauser DM, Frevert EU, Boulton DW. Grapefruit juice alters plasma sertraline levels after single ingestion of sertraline in healthy volunteers. World J Biol Psychiatry. 2009;10(4, pt 3):832-835.19172438
Uesawa Y, Mohri K. Relationship between lipophilicities of 1,4-dihydropyridine derivatives and pharmacokinetic interaction strengths with grapefruit juice. Yakugaku Zasshi. 2008;128(1):117-22.18176062
Undre NA, Moloney FJ, Ahmadi S, Stevenson P, Murphy GM. Skin and systemic pharmacokinetics of tacrolimus following topical application of tacrolimus ointment in adults with moderate to severe atopic dermatitis. Br J Dermatol. 2009;160(3):665-669.19076975
Vaidyanathan S, Camenisch G, Schuetz H, et al. Pharmacokinetics of the oral direct renin inhibitor aliskiren in combination with digoxin, atorvastatin, and ketoconazole in healthy subjects: the role of p-glycoprotein in the disposition of aliskiren. J Clin Pharmacol. 2008;48(11):1323-1338.18784280
Valenzuela B, Rebollo J, Pérez T, Brugarolas A, Pérez-Ruixo JJ. Effect of grapefruit juice on the pharmacokinetics of docetaxel in cancer patients: a case report. Br J Clin Pharmacol. 2011;72(6):978-981.21692829
van Agtmael MA, Gupta V, van der Graaf CA, et al. The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects. Clin Pharmacol Ther. 1999;66(4):408-414.10546925
van Agtmael MA, Gupta V, van der Wosten TH, et al. Grapefruit juice increases the bioavailability of artemether. Eur J Clin Pharmacol. 1999;55(5):405-410.10456492
van Breemen RB, Pajkovic N. Multitargeted therapy of cancer by lycopene. Cancer Lett. 2008;269(2):339-351.18585855
van der Velden W, Huussen J, Ter Laak H, de Sévaux R. Colchicine-induced neuromyopathy in a patient with chronic renal failure: the role of clarithromycin. Neth J Med. 2008;66(5):204-206.18490798
van Erp NP, Baker SD, Zandvliet AS, et al. Marginal increase of sunitinib exposure by grapefruit juice. Cancer Chemother Pharmacol. 2011;67(3):695-703.20512335
Viibryd (vilazodone) [prescribing information]. New Haven, CT: Trovis Pharmaceuticals; January 2011.
Vincent J, Harris SI, Foulds G, et al. Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine. Br J Clin Pharmacol. 2000;50(5):455-463.11069440
Votrient (pazopanib) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; October 2009.
Xalkori (crizotinib) [prescribing information]. New York, NY: Pfizer; August 2011.
Xarelto (rivaroxaban) [product monograph]. Toronto, Canada: Bayer; September 2008.
Wakasugi H, Yano I, Ito T, et al. Effect of clarithromycin on renal excretion of digoxin: interaction with P-glycoprotein. Clin Pharmacol Ther. 1998;64(1):123-128.9695727
Wason S, DiGiacinto JL, Davis MW. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther. 2012;34(10):2161-2173.22940371
Yee GC, Stanley DL, Ruiz J, et al. Effect of grapefruit juice on oral cyclosporine pharmacokinetics. Pharmacotherapy. 1994;14:377.
Yee GC, Stanley DL, Pessa LJ, et al. Effect of grapefruit juice on blood cyclosporine concentration. Lancet. 1995;345(8955):955-956.7715295
Yee GC, Adams VR, Pessa L, et al. Comparison on one versus two doses of grapefruit juice on oral cyclosporine pharmacokinetics. Pharmacotherapy. 1997;17:1112.
Yussim A, Bar-Nathan M, Lustig S, et al. Gastrointestinal, hepatorenal, and neuromuscular toxicity caused by cyclosporine-colchicine interaction in renal transplantation. Transplant Proc. 1994;26(5):2825-2826.7940890
Zaidenstein R, Dishi V, Gips M, et al. The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil. Eur J Clin Pharmacol. 1998;54(4):337-340.9696960
Zitron E, Scholz E, Owen RW, et al. QTc prolongation by grapefruit juice and its potential pharmacological basis: HERG channel blockade by flavonoids. Circulation. 2005;111(7):835-838.15710766
Zocor (simvastatin) [prescribing information]. Whitehouse Station, NJ: Merck and Co; June 2011.
Zortress (everolimus) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; March 2010.

Disclaimer

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

More about grapefruit

Consumer resources

Hide