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.
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
Abbas R, Hug BA, Leister C, Burns J, Sonnichsen D. Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects.
Br J Clin Pharmacol. 2011;71(4):522-527.21395644
Abdlekawy KS, Donia AM, Elbarbry F. Effects of grapefruit juice and pomegranate juice on the pharmacokinetic properties of dapoxetine and midazolam in healthy subjects.
Eur J Drug Metab Pharmacokinet. 2017;42(3):397-405.27294349
Abilify (amiodarone) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; February 2011.
Abilify Maintena (aripiprazole) [prescribing information]. Rockville, MD: Otsuka America Pharmaceutical, Inc., February 2013.
Acetaminophen and Codeine Phosphate Oral Solution [prescribing information]. Morton Grove, IL: Morton Grove Pharmaceuticals, Inc.; November 2017.
Addyi (flibanserin) [prescribing information]. Raleigh, NC: Sprout Pharmaceuticals Inc; August 2015.
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.
Agosti S, Casalino L, Bertero G, et al. A dangerous fruit juice.
Am J Emerg Med. 2012;30(1):248.e5-248.e8.20970282
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
Alderman CP, Gebauer MG, Gilbert AL, Condon JT. Possible interaction of zopiclone and nefazodone.
Ann Pharmacother. 2001;35(11):1378-1380. [PubMed 11724087]9448208
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
Altoprev (lovastatin) extended-release tablet [prescribing information]. Zug, Switzerland: Covis Pharma; September 2020.
Alunbrig (brigatinib) [prescribing information]. Cambridge, MA: Takeda Pharmaceutical Company Limited; April 2017.Alunbrig.2017.04
Ando A, Oshida K, Fukuyama S, Watanabe A, Hashimoto H, Miyamoto Y. Identification of human cytochrome P450 enzymes involved in the metabolism of a novel kappa-opioid receptor agonist, nalfurafine hydrochloride.
Biopharm Drug Dispos. 2012;33(5):257-264.22581509
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
Apadaz (benzhydrocodone and acetaminophen) [prescribing information]. Coralville, IA: KemPharm Inc; February 2018.
Apo-Domperidone (domperidone) [product monograph]. Toronto, Ontario, Canada: Apotex Inc.; March 2015.
Aranko K, Luurila H, Backman JT, Neuvonen PJ, Olkkola KT. The effect of erythromycin on the pharmacokinetics and pharmacodynamics of zopiclone.
Br J Clin Pharmacol. 1994;38(4):363-367.7833227
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. Fruit juice inhibition of uptake transport: a new type of food-drug interaction.
Br J Clin Pharmacol. 2010;70(5):645-655.21039758
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, 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, 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, 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, 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, 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, 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
Bailey DG, Spence JD, Munoz C, Arnold JM. Interaction of citrus juices with felodipine and nifedipine.
Lancet. 1991;337(8736):268-269.1671113
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
Becquemont L, Mouaijah S, Escaffre O, Beaune P, Funck-Brentano C, Jaillon P. Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism.
Drug Metab Dispos. 1999;27(9):1068-1073.10460808
Belsomra (suvorexant) [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; August 2014.
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
Bidstrup TB, Damkier P, Olsen AK, Ekblom M, Karlsson A, Brosen K. The impact of CYP2C8 polymorphism and grapefruit juice on the pharmacokinetics of repaglinide.
Br J Clin Pharmacol. 2006;61(1):49-57.16390351
Biltricide (praziquantel) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; January 2019.
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
Blondin MC, Beauregard H, Serri O. Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review.
Endocr Pract. 2013;19(6):e138-e141.23807527
Boinpally R, Gad N, Gupta S, Periclou A. Influence of CYP3A4 induction/inhibition on the pharmacokinetics of vilazodone in healthy subjects.
Clin Ther. 2014;36(11):1638-1649.25236915
Bolland MJ, Bagg W, Thomas MG, Lucas JA, Ticehurst R, Black PN. Cushing's syndrome due to interaction between inhaled corticosteroids and itraconazole.
Ann Pharmacother. 2004;38(1):46-49.14742792
Boni JP, Leister C, Burns J, Hug B. Differential effects of ketoconazole on exposure to temsirolimus following intravenous infusion of temsirolimus.
Br J Cancer. 2008;98(11):1797-1802.18458675
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 2015.
Bower S, Hull CJ. Comparative pharmacokinetics of fentanyl and alfentanil.
Br J Anaesth. 1982;54(8):871-877.6125162
Braftovi (encorafenib) [prescribing information]. Boulder, CO: Array BioPharma Inc.; April 2020.
Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel.
J Thromb Haemost. 2007;5:2429-2436.17900275
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
Buspirone [prescribing information]. Laurelton, NY: Epic Pharma LLC; May 2020.
Cabometyx (cabozantinib) tablets [prescribing information]. South San Francisco, CA: Exelixis Inc; April 2016.
Calquence (acalabrutinib) [prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; October 2017.
Carper J. Grapefruit. In:
The Food Pharmacy: Dramatic New Evidence That Food is Your Best Medicine. New York, NY: Bantam Books; 1988:213-215.
Castro N, Jung H, Medina R, Gonzalez-Esquivel D, Lopez M, Sotelo J. Interaction between grapefruit juice and praziquantel in humans.
Antimicrob Agents Chemother. 2002;46(5):1614-1616.11959616
Cenestin (synthetic conjugated estrogens, A) [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA Inc; November 2020.
Cerdelga (eliglustat) [prescribing information]. Waterford, Ireland: Genzyme Ireland Ltd; August 2014.
Chang SH, Chou IJ, Yeh YH, et al. Association between use of non-vitamin K oral anticoagulants with and without concurrent medications and risk of major bleeding in nonvalvular atrial fibrillation.
JAMA. 2017;318(13):1250-1259.28973247
Charbit B, Becquemont L, Lepere B, Peytavin G, Funck-Brentano C. Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine.
Clin Pharmacol Ther. 2002;72(5):514-523.12426515
Chateal EQ (ethinyl estradiol and levonorgestrel) [prescribing information]. Charleston, SC: Afaxys Pharma, LLC; June 2021.
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
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
Choudhury L, Grais IM, Passman RS. Torsades de pointes due to drug interaction between disopyramide and clarithromycin.
Heart Dis. 1999;1(4):206-207.11720625
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.
Clemens JQ, Erickson DR, Varela NP, Lai HH. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome.
J Urol. 2022;208(1):34-42. doi:10.1097/JU.000000000000275635536143
Clopixol (zuclopenthixol) [product monograph]. Montreal, Quebec: Lundbeck Canada; January 2011.
Coartem (artemether and lumefantrine) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; August 2019.
Codipin (benidipine hydrochloride) tablets [Korea KR prescribing information]. Available at: http://drug.mfds.go.kr/html/bxsSearchDrugProduct.jsp?item_Seq=199300958. Accessed October 26, 2017.
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: Mutual Pharmaceutical Company Inc; July 2009.
Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study.
Lancet. 2009;373(9660):309-317.19108880
Cometriq (cabozantinib) [prescribing information]. San Francisco, CA: Exelixis; November 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
Corlanor (ivabradine) [prescribing information]. Thousand Oaks, CA: Amgen Inc.; May 2019.
Cotellic (cobimetinib) [prescribing information]. South San Francisco, CA: Genetech USA Inc; November 2015
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
Cycloset (bromocriptine) [prescribing information]. Tiverton, RI: VeroScience, LLC; October 2015.
Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine.
Br J Clin Pharmacol. 1999;48(6):829-838.10594487
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
de Jong J, Skee D, Murphy J, et al. Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants.
Pharmacol Res Perspect. 2015;3(4):e00156.26171235
Demerol (meperidine) [prescribing information]. Lake Forest, IL: Hospira, Inc.; December 2016.
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 Wachter E, Malfroot A, De Schutter I, Vanbesien J, De Schepper J. Inhaled budesonide induced Cushing's syndrome in cystic fibrosis patients, due to drug inhibition of cytochrome P450.
J Cyst Fibros. 2003;2(2):72-75.15463853
De Wachter E, Vanbesien J, De Schutter I, Malfroot A, De Schepper J. Rapidly developing Cushing syndrome in a 4-year-old patient during combined treatment with itraconazole and inhaled budesonide.
Eur J Pediatr. 2003;162(7-8):488-489.12719971
Diflucan (fluconazole) [prescribing information]. New York, NY: Pfizer Inc.; September 2020.
Dirix L, Swaisland H, Verheul HM, et al. Effect of itraconazole and rifampin on the pharmacokinetics of olaparib in patients with advanced solid tumors: results of two phase I open-label studies.
Clin Ther. 2016;38(10):2286-2299.27745744
Dixit V, Hariparsad N, Li F, Desai P, Thummel KE, Unadkat JD. Cytochrome P450 enzymes and transporters induced by anti-human immunodeficiency virus protease inhibitors in human hepatocytes: implications for predicting clinical drug interactions.
Drug Metab Dispos. 2007;35(10): 1853-1859.17639026
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
Dreier JP, Endres M. Statin-associated rhabdomyolysis triggered by grapefruit consumption.
Neurology. 2004;62(4):670.14981197
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
Dutreix C, Munarini F, Lorenzo S, Roesel J, Wang Y. Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers.
Cancer Chemother Pharmacol. 2013;72(6):1223-1234.24085261
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 DJ, 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.
Effient (prasugrel) [prescribing information]. Indianapolis, IN: Eli Lily and Company; July 2009.
Eissing T, Lippert J, Willmann S. Pharmacogenomics of codeine, morphine, and morphine-6-glucuronide: model-based analysis of the influence of CYP2D6 activity, UGT2B7 activity, renal impairment, and CYP3A4 inhibition.
Mol Diagn Ther. 2012;16(1):43-53.22352453
Eliquis (apixaban) [prescribing information]. New York, NY: Pfizer Inc; July 2016.
Eliquis (apixaban) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada Inc.; June 2016.
ella (ulipristal acetate) [prescribing information]. Morristown, NJ: Watson Pharma Inc; August 2010.
Emend (aprepitant) [prescribing information]. Whitehouse Station, NJ: Merck & Co Inc; August 2015.
Emend (fosaprepitant) [prescribing information]. Whitehouse Station, NJ: Merck & Co Inc; April 2018.
Emflaza (deflazacort) [prescribing information]. South Plainfield, NJ: PTC Therapeutics Inc.; June 2021.
Enjuvia (synthetic conjugated estrogens, B) [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA Inc; March 2010.
Ensminger ME, Ensminger AH. Grapefruit. In:
Foods & Nutrition Encyclopedia. Vol 1. 2nd ed. Boca Raton, FL: CRC Press; 1993:1097-1099.
Entocort EC (budesonide) capsules [prescribing information]. San Diego, CA: Prometheus Laboratories Inc; December 2011.
Envarsus XR (tacrolimus extended-release tablets) [prescribing information]. Cary, NC: Veloxis Pharmaceuticals, Inc.; September 2020.
Epidiolex (cannabidiol) oral solution [prescribing information]. Carlsbad, CA: Greenwich Biosciences Inc; June 2018.
Ernst E. Herbal medicinal products during pregnancy: are they safe?
BJOG. 2002;109(3):227-235.11950176
Esbriet (pirfenidone) [product monograph]. Mississauga, Ontario, Canada: Hoffmann-La Roche Limited; August 2021.
Esbriet (pirfenidone) [prescribing information]. South San Francisco, CA: Genentech USA Inc; July 2019.
Estrace (estradiol) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co.; March 2005.
Estragyn (estrone) vaginal cream [prescribing information]. Montreal, Quebec, Canada: Searchlight Pharma Inc; August 2016.
Fareston (toremifene) [prescribing information]. Memphis, TN: GTx Inc; March 2011.
Farid NA, Payne CD, Small DS, et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently.
Clin Pharmacol Ther. 2007;81(5):735-741.17361128
Farydak (panobinostat) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; February 2015.
Felodipine extended-release tablets [prescribing information]. Las Vegas, NV: Yiling Pharmaceutical Ltd; July 2018.
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
Fibristal (ulipristal acetate) [product monograph]. Mississauga, ON: Actavis Specialty Pharmaceuticals Co; June 2013.
Flockhart DA, Drici MD, Kerbusch T, et al. Studies on the mechanism of a fatal clarithromycin-pimozide interaction in a patient with Tourette syndrome.
J Clin Psychopharmacol. 2000;20(3):317-324.10831018
Flomax (tamsulosin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; October 2014.
Frankel JK, Packer CD. Cushing's syndrome due to antiretroviral-budesonide interaction.
Ann Pharmacother. 2011;45(6):823-824.21558486
Fuhr U, Klittich K, Staib AH. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man.
Br J Clin Pharmacol. 1993;35(4):431-436.8485024
Fuhr U, Maier A, Keller A, Steinijans VW, Sauter R, Staib A. Lacking effect of grapefruit juice on theophylline pharmacokinetics.
Int J Clin Pharmacol Ther. 1995;33(6):311-314.7582380
Fuhr U, Maier-Bruggemann A, Blume H, et al. Grapefruit juice increases oral nimodipine bioavailability.
Int J Clin Pharmacol Ther. 1998;36(3):126-132.9562227
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
Fujiwara Y, Toyoda M, Chayahara N, et al. Effects of aprepitant on the pharmacokinetics of controlled-release oral oxycodone in cancer patients.
PLoS One. 2014;9(8):e104215.25121773
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
Fyarro (sirolimus) protein-bound [prescribing information]. Pacific Palisades, CA: Aadi Bioscience Inc; November 2021.
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
Gasche Y, Daali Y, Fathi M, et al. Codeine intoxication associated with ultrarapid CYP2D6 metabolism.
N Engl J Med. 2004;351(27):2827-2831.15625333
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
Gleevec (imatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; August 2020.
Gloperba (colchicine) oral solution [prescribing information]. Woburn, MA: ROMEG Therapeutics, LLC; January 2019.
Goel S, Cohen M, Comezoglu SN, et al. The effect of ketoconazole on the pharmacokinetics and pharmacodynamics of ixabepilone: a first in class epothilone B analogue in late-phase clinical development.
Clin Cancer Res. 2008;14(9):2701-2709.18451235
Goldbart A, Press J, Sofer S, Kapelushnik J. Near fatal acute colchicine intoxication in a child. A case report.
Eur J Pediatr. 2000;159(12):895-897.11131346
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
Gowarty JL, Herrington JD. Verapamil as a culprit of palbociclib toxicity.
J Oncol Pharm Pract. 2019;25(3):743-746.29523051
Grande LA, Mendez RD, Krug RT, Verschuyl EJ. Attention—grapefruit!
Lancet. 2009;373(9670):1222.19345832
Gray D, Roux P, Carrihill M, Klein M. Adrenal suppression and Cushing's syndrome secondary to ritonavir and budesonide.
S Afr Med J. 2010;100(5):296-297.20460021
Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice.
Clin Pharmacol Ther. 2003;74(2):121-129.12891222
Gross AS, Goh YD, Addison RS, Shenfield GM. Influence of grapefruit juice on cisapride pharmacokinetics.
Clin Pharmacol Ther. 1999;65(4):395-401.10223776
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
Gu H, Dutreix C, Rebello S, et al. Simultaneous physiologically based pharmacokinetic (PBPK) modeling of parent and active metabolites to investigate complex CYP3A4 drug-drug interaction potential: a case example of midostaurin.
Drug Metab Dispos. 2019;46(2):109-121.29117990
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
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
Hamberg P, Woo MM, Chen LC, et al. Effect of ketoconazole-mediated CYP3A4 inhibition on clinical pharmacokinetics of panobinostat (LBH589), an orally active histone deacetylase inhibitor.
Cancer Chemother Pharmacol. 2011;68(3):805-813.21706316
Hanley MJ, Masse G, Harmatz JS, et al. Effect of blueberry juice on clearance of buspirone and flurbiprofen in human volunteers.
Br J Clin Pharmacol. 2013;75(4):1041-1052.22943633
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
Hayashi Y, Ikeda U, Hashimoto T, Watanabe T, Mitsuhashi T, Shimada K. Torsades de pointes ventricular tachycardia induced by clarithromycin and disopyramide in the presence of hypokalemia.
Pacing Clin Electrophysiol. 1999;22(4 pt 1):672-674.10234723
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
Hermans K, Stockman D, Van den Branden F. Grapefruit and tonic: a deadly combination in a patient with the long QT syndrome.
Am J Med. 2003;114(6):511-512.12727589
Ho PC, Chalcroft SC, Coville PF, Wanwimolruk S. Grapefruit juice has no effect on quinine pharmacokinetics.
Eur J Clin Pharmacol. 1999;55(5):393-398.10456490
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 PC, Saville DJ, Wanwimolruk S. Inhibition of human CYP3A4 activity by grapefruit flavonoids, furanocoumarins and related compounds.
J Pharm Pharm Sci. 2001;4(3):217-227.11737987
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, 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
Hsyu PH, Pignataro DS, Matschke K. Effect of aprepitant, a moderate CYP3A4 inhibitor, on bosutinib exposure in healthy subjects.
Eur J Clin Pharmacol. 2017;73(1):49-56.27718000
Hu J, Shang D, Xu X, et al. 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
Hughes TE, Stansfield L, Kumar P, Worthy TY, Tian X, Childs RW. A prospective evaluation on the interaction of fluconazole and voriconazole on serum concentrations of budesonide in patients treated for gastrointestinal GVHD.
Bone Marrow Transplant. 2020;55(6):1085-1092.31953533
Hulot JS, Bura A, Villard E, et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects.
Blood. 2006;108:2244-2247.16772608
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
Ibrance (palbociclib) capsule [prescribing information]. New York, NY: Pfizer Inc; September 2019.
Ibrance (palbociclib) tablet [prescribing information]. New York, NY: Pfizer Inc; November 2019.
Iclusig (ponatinib) [prescribing information]. Cambridge, MA: Millennium Pharmaceuticals; December 2020.
Ieiri I, Doi Y, Maeda K, et al. Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose.
J Clin Pharmacol. 2012;52(7):1078-1089.21593283
Ilaxten (bilastine) [summary of product characteristics]. Buckinghamshire, United Kingdom: A Menarini Farmaceutica Internazionale SRL; January 2012.
Ifex (ifosfamide) [prescribing information]. Deerfield, IL: Baxter Healthcare; March 2012.
Iida H, Morita T, Suzuki E, Iwasawa K, Toyo-oka T, Nakajima T. Hypoglycemia induced by interaction between clarithromycin and disopyramide.
Jpn Heart J. 1999;40(1):91-96.10370402
Imbruvica (ibrutinib) [prescribing information]. Horsham, PA: Janssen Biotech Inc; August 2017.
Imovane (zopiclone) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada Inc; October 2014.
Inlyta (axitinib) [prescribing information]. New York, NY: Pfizer; January 2020.
Inrebic (fedratinib) [prescribing information]. Summit, NJ: Celgene Corporation; August 2019.
Inspra (eplerenone) [prescribing information]. New York, NY: Pfizer; May 2016.
Inspra (eplerenone) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada Inc; June 2014.
Intuniv (guanfacine) [prescribing information]. Wayne, PA: Shire US Inc; July 2016.
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
Ixempra (ixabepilone) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; October 2011.
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.
Jalava KM, Olkkola KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone.
Eur J Clin Pharmacol. 1996;51(3-4):331-334.9010708
Jalyn (dutasteride and tamsulosin) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; November 2017.
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
Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil.
Clin Pharmacol Ther. 2002;71(1):21-29.11823754
Johnson FM, Agrawal S, Burris H, et al. Phase 1 pharmacokinetic and drug-interaction study of dasatinib in patients with advanced solid tumors.
Cancer. 2010;116(6):1582-1591.20108303
Johnson BF, Cheng SL and Venitz J. Transient kinetic and dynamic interactions between verapamil and dofetilide, a class III antiarrhythmic.
J Clin Pharmacol. 2001;41(11):1248-1256.11697758
Jones W, Chastain CA, Wright PW. Iatrogenic cushing syndrome secondary to a probable interaction between voriconazole and budesonide.
Pharmacotherapy. 2014;34(7):e116-e119.24757038
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):1651-1656.11036110
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.
Jynarque (tolvaptan) [prescribing information]. Rockville, MD: Otsuka America Pharmaceutical, Inc.; April 2018.
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
Kazui M, Nishiya Y, Ishizuka T, et al. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite.
Drug Metab Dispos. 2010;38(1):92-99.19812348
Kedem E, Shahar E, Hassoun G, Pollack S. Iatrogenic Cushing's syndrome due to coadministration of ritonavir and inhaled budesonide in an asthmatic human immunodeficiency virus infected patient.
J Asthma. 2010;47(7):830-831.20653496
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
Kharasch ED, Whittington D, Hoffer C. Influence of hepatic and intestinal cytochrome P4503A activity on the acute disposition and effects of oral transmucosal fentanyl citrate.
Anesthesiology. 2004;101(3):729-737.15329598
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
Kimura S, Kako S, Wada H, et al. Can grapefruit juice decrease the cost of imatinib for the treatment of chronic myelogenous leukemia?
Leuk Res. 2011;35(1):e11-e12.20952061
Kisqali (ribociclib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2020.
Kivisto KT, Lilja JJ, Backman JT, et al. 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
Korlym (mifepristone) [prescribing information]. Menlo Park, CA: Corcept Therapeutics Incorporated; November 2019.
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, Meier PJ, Krähenbühl S. Interaction between grapefruit juice and midazolam in humans.
Clin Pharmacol Ther. 1995;58(1):20-28.7628179
Lalovic B, Phillips B, Risler LL, Howald W, Shen DD. Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes.
Drug Metab Dispos. 2004;32(4):447-454.15039299
Latuda (lurasidone) [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals; July 2013.
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. Determination of sildenafil citrate in plasma by high-performance liquid chromatography and a case for the potential interaction of grapefruit juice with sildenafil citrate.
Ther Drug Monit. 2001;23(1):21-26.11206038
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
Lefevre G, Carpenter P, Souppart C, et al. Pharmacokinetics and electrocardiographic pharmacodynamics of artemether-lumefantrine (Riamet) with concomitant administration of ketoconazole in healthy subjects.
Br J Clin Pharmacol. 2002;54(5):485-492.12445027
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
Lercanidipine [summary of product characteristics]. Devon, UK: Arrow Generics Limited; November 2013.
Levotension (levamlodipine) [Korean product monograph]. Anguk Pharmaceutical; February 2010.
Lexiva (fosamprenavir) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; March 2019.
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, Backman JT, Laitila J, Luurila H, Neuvonen PJ. Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol.
Clin Pharmacol Ther. 2003;73(3):192-198.12621384
Lilja JJ, Juntti-Patinen L, Neuvonen PJ. Orange juice substantially reduces the bioavailability of the beta-adrenergic-blocking agent celiprolol.
Clin Pharmacol Ther. 2004;75(3):184-190.15001969
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 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. 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, 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
Ling SY, Huizinga RB, Mayo PR, et al. Cytochrome P450 3A and P-glycoprotein drug-drug interactions with voclosporin.
Br J Clin Pharmacol. 2014;77(6):1039-1050.24330024
Lipitor (atorvastatin) [prescribing information]. New York, NY: Pfizer; June 2009.
Lipitor (atorvastatin) [prescribing information]. New York, NY: Pfizer Inc; November 2020.
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
Lonasen (blonanserin) [KR prescribing information]. Available at: http://drug.mfds.go.kr/html/bxsSearchDrugProduct.jsp?item_Seq=200906540. Accessed September 22, 2014.
Lovastatin [prescribing information]. Baltimore, MD: Lupin Pharmaceuticals, Inc.; June 2019.
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):2545-2553.9153299
Lu WJ, Huang K, Lai ML, Huang JD. Erythromycin alters the pharmacokinetics of bromocriptine by inhibition of organic anion transporting polypeptide C-mediated uptake.
Clin Pharmacol Ther. 2006;80(4):421-422.17015059
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
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
Lupkynis (voclosporin) [prescribing information]. Rockville, MD: Aurinia Pharma US Inc; January 2021.
Lynparza (olaparib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; January 2018.
Main KM, Skov M, Sillesen IB, et al. Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient.
Acta Paediatr. 2002;91(9):1008-1011.12412882
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
Mazokopakis EE. Unusual causes of rhabdomyolysis.
Intern Med J. 2008;38(5):364-367.18402564
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
Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel.
N Engl J Med. 2009;360(4):354-362.19106084
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
Menest (esterified estrogens) [prescribing information]. New York, NY: Pfizer Inc; April 2019.
Menna P, Salvatorelli E, Del Principe MI, et al. Choosing antifungals for the midostaurin-treated patient: does CYP3A4 outweigh recommendations? A brief insight from real life.
Chemotherapy. 2021;66(1-2):47-52. doi:10.1159/00051398933677444
Mevacor (lovastatin) [prescribing information]. Whitehouse Station, NJ: Merck & Co; February 2014.
Mifeprex (mifepristone) [prescribing information]. New York, NY: Danco Laboratories, LLC; April 2019.
Mignat C, Wille U, Ziegler A. Affinity profiles of morphine, codeine, dihydrocodeine and their glucuronides at opioid receptor subtypes.
Life Sci. 1995;56(10):793-799.7885194
Min DI, Ku YM, Geraets DR, Lee H. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers.
J Clin Pharmacol. 1996;36(5):469-476.8739026
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
Mitigare (colchicine) capsule [prescribing information]. Memphis, TN: Hikma Americas, Inc.; September 2014.
Molto J, Rajoli R, Back D, et al. Use of a physiologically based pharmacokinetic model to simulate drug-drug interactions between antineoplastic and antiretroviral drugs.
J Antimicrob Chemother. 2017;72(3):805-811.27999009
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
Motens (lacidipine) [summary of product characteristics]. Middlesex, United Kingdom: GSK UK; September 2013.
Movantik (naloxegol) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; September 2014.
Multaq (dronedarone) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US LLC; March 2014.
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
Mvix 50 mg tablet (mirodenafil) [KR prescribing information]. http://drug.mfds.go.kr/html/bxsSearchDrugProduct.jsp?item_Seq=200708298. Accessed April 7, 2016.
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
Nakagawa K, Goto T. Effects of ingestion of grapefruit juice or grapefruit on the hypotensive effect and plasma concentrations of dihydropyridine calcium antagonists (amlodipine and nifedipine): a case study.
Clin Exp Hypertens. 2010;32(2):71-75.20374180
Narasimhan NI, Dorer DJ, Niland K, Haluska F, Sonnichsen D. Effects of ketoconazole on the pharmacokinetics of ponatinib in healthy subjects.
J Clin Pharmacol. 2013;53(9):974-981.23801357
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
Nelson MV, Berchou RC, Kareti D, LeWitt PA. Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine.
Clin Pharmacol Ther. 1990;47(6):694-697.2357864
Nerlynx (neratinib) [prescribing information]. Los Angeles, CA: Puma Biotechnology Inc; July 2017.
Nexterone (amiodarone) [prescribing information]. Deerfield, IL: Baxter Healthcare Corporation; November 2016.
Nguyen D, Mizne S. Effects of ketoconazole on the pharmacokinetics of mifepristone, a competitive glucocorticoid receptor antagonist, in healthy men.
Adv Ther. 2017;34(10):2371-2385.29022184
Nieminen TH, Hagelberg NM, Saari TI, et al. Grapefruit juice enhances the exposure to oral oxycodone.
Basic Clin Pharmacol Toxicol. 2010;107(4):782-788.20406214
Nisoldipine [prescribing information]. Morgantown, WV: Mylan Pharmaceuticals, Inc; June 2017.
Norpace (disopyramide) [prescribing information]. New York, NY: Pfizer Inc; August 2016.
NuvaRing (etonogestrel and ethinyl estradiol) vaginal ring [prescribing information]. Whitehouse Station, NJ: Merck & Co Inc; January 2020.
Nymalize (nimodipine) [prescribing information]. Atlanta, GA: Arbor Pharmaceuticals Inc; May 2013.
Odomzo (sonidegib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; July 2015.
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
Ogen (estropipate) [prescribing information]. New York, NY: Pfizer Inc; May 2019.
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
Olysio (simeprevir) [prescribing information]. Titusville, NJ: Janssen Products, LP, November 2013.
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]. Horsham, PA: Teva Pharmaceuticals USA; March 2014.
Orladeyo (berotralstat) [prescribing information]. Durham, NC: BioCryst Pharmaceuticals, Inc.; December 2020.
Ortikos (budesonide) extended-release capsules [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; June 2019.
OxyContin (oxycodone hydrochloride controlled-release) [prescribing information]. Stamford, CT: Purdue Pharma L.P.; August 2015.
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
Paar D, Terjung B, Sauerbruch T. Life-threatening interaction between clarithromycin and disopyramide.
Lancet. 1997;349(9048):326-327.9024381
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
Parlodel (bromocriptine) [prescribing information]. Suffern, NY: Novartis Pharmaceuticals Corporation; January 2012.
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
Peltoniemi MA, Saari TI, Hagelberg NM, Laine K, Neuvonen PJ, Olkkola KT. S-ketamine concentrations are greatly increased by grapefruit juice.
Eur J Clin Pharmacol. 2012;68(6):979-986.22286159
Penzak SR, Acosta EP, Turner M, et al. Effect of Seville orange juice and grapefruit juice on indinavir pharmacokinetics.
J Clin Pharmacol. 2002;42(10):1165-1170.12362932
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
Piscitelli SC, Kress DR, Bertz RJ, et al. The effect of ritonavir on the pharmacokinetics of meperidine and normeperidine.
Pharmacotherapy. 2000;20:549-553.10809341
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
Pletal (cilostazol) [prescribing information]. Rockville, MD: Otsuka America Pharmaceutical, Inc.; July 2015.
Pohl O, Osterloh I, Gotteland JP. Effects of erythromycin at steady-state concentrations on the pharmacokinetics of ulipristal acetate.
J Clin Pharm Ther. 2013;38(6):512-517.24102384
Pomalyst (pomalidomide) [prescribing information]. Summit, NJ: Celgene Corporation; February 2013.
Premarin (conjugated estrogens) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals, Inc.; December 2014.
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
Priligy (dapoxetine) [summary of product characteristics]. Wooburn Green, Buckinghamshire, United Kingdom: A. Menarini Farmaceutica Internazionale SRL; December 2013.
Priligy (dapoxetine) [summary of product characteristics]. Mapletree Business City, Singapore: A. Menarini Singapore Pte. Ltd.; September 2013.
Procardia (nifedipine) [prescribing information]. New York, NY: Pfizer Inc; January 2015.
Procardia XL (nifedipine) [prescribing information]. New York, NY: Pfizer Inc; January 2015.
Prograf (tacrolimus) [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc.; February 2015.
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.
Qualaquin (quinine) [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries Inc; June 2019.
Quinidine gluconate [prescribing information]. Philadelphia, PA: Mutual Pharmaceutical Co; February 2010.
Raaska K, Niemi M, Neuvonen M, Neuvonen PJ, Kivisto KT. Plasma concentrations of inhaled budesonide and its effects on plasma cortisol are increased by the cytochrome P4503A4 inhibitor itraconazole.
Clin Pharmacol Ther. 2002;72(4):362-369.12386638
Ragosta M, Weihl AC, Rosenfeld LE. Potentially fatal interaction between erythromycin and disopyramide.
Am J Med. 1989;86(4):465-466.2467560
Rakhit A, Pantze MP, Fettner S, et al. The effects of CYP3A4 inhibition on erlotinib pharmacokinetics: computer-based simulation (SimCYP) predicts in vivo metabolic inhibition.
Eur J Clin Pharmacol. 2008;64(1):31-41.18000659
Ramirez J, Innocenti F, Shuetz EG, et al. CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes.
Drug Metab Dispos. 2004;32:930-936.15319333
Ramitch (nalfurafine) capsule [KR prescribing information]. Available at: http://drug.mfds.go.kr/html/bxsSearchDrugProduct.jsp?item_Seq=201307707. Accessed May 2017.
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.
Rapamune (sirolimus) [prescribing information]. Philadelphia, PA: Pfizer Inc.; April 2017.
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
Reddy P, Ellington D, Zhu Y, et al. Serum concentrations and clinical effects of atorvastatin in patients taking grapefruit juice daily.
Br J Clin Pharmacol. 2011;72(3):434-441.21501216
Reif S, Nicolson MC, Bisset D, et al. Effect of grapefruit juice intake on etoposide bioavailability.
Eur J Clin Pharmacol. 2002;58(7):491-494.12389073
Relpax (eletriptan) [prescribing information]. New York, NY: Pfizer Inc; November 2013.
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.
Rexulti (brexpiprazole) [prescribing information]. Rockville, MD: Otsuka America Pharmaceuticals, Inc.; July 2015.
Rogers JD, Zhao J, Liu L. Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
Clin Pharmacol Ther. 1999;66(4):358-366.10546919
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
Rozlytrek (entrectinib) [prescribing information]. South San Francisco, CA: Genentech USA, Inc.; August 2019.
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
Rupafin (rupatadine) [Singapore prescribing information]. Alcobendas, Madrid, Spain: Italfarmaco, S.A.; October 2015.
Rupall (rupatadine) [product monograph]. Verdun, Quebec, Canada: Medexus Pharmaceuticals Inc; June 2020.
Rupatadine [UK summary of product characteristics]. Palau-solita i Plegamans, Spain: J. Uriach & Cia., S.A.; September 2020.
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
Rydapt (midostaurin) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; April 2017.
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
Samant TS, Huth F, Umehara K, et al. Ribociclib drug-drug interactions: clinical evaluations and physiologically-based pharmacokinetic modeling to guide drug labeling.
Clin Pharmacol Ther. 2020;108(3):575-585.32557601
Samsca (tolvaptan) [prescribing information]. Tokyo, Japan: Otsuka Pharmaceutical; May 2009.
Sativex (tetrahydrocannabinol and cannabidiol oromucosal spray) [UK summary of product characteristics]. Wiltshire, UK: GW Pharma Ltd; February 2014.
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
Schubert W, Cullberg G, Edgar B, Hedner T. Inhibition of 17 beta-estradiolmetabolism by grapefruit juice in ovariectomized women.
Maturitas. 1994;20(2-3):155-163.7715468
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
Seidegard J. Reduction of the inhibitory effect of ketoconazole on budesonide pharmacokinetics by separation of their time of administration.
Clin Pharmacol Ther. 2000;68(1):13-17.10945311
Selectol (celiprolol) [KR product information]. Available at: http://drug.mfds.go.kr/html/bxsSearchDrugProduct.jsp?item_Seq=200001290. Accessed July 13, 2017.
Serevent (salmeterol) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; March 2008.
Shang DW, Wang ZZ, Hu HT, et al. Effects of food and grapefruit juice on single-dose pharmacokinetics of blonanserin in healthy Chinese subjects.
Eur J Clin Pharmacol. 2018;74(1):61-67.28975417
Shelton MJ, Wynn HE, Hewitt RG, DiFrancesco R. Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects.
J Clin Pharmacol. 2001;41(4):435-442.11304900
Sheu MT, Wu AB, Yeh GC, Hsia A, Ho HO. Development of a liquid chromatographic method for bioanalytical applications with sildenafil.
J Chromatogr B Analyt Technol Biomed Life Sci. 2003;791(1-2):255-262.12798185
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
Shin KH, Chung YJ, Kim BH, et al. Effect of ketoconazole on the pharmacokinetics of udenafil in healthy Korean subjects.
Br J Clin Pharmacol. 2010;69(3):307-310.20233203
Shin KH, Kim BH, Kim TE, et al. The effects of ketoconazole and rifampicin on the pharmacokinetics of mirodenafil in healthy Korean male volunteers: an open-label, one-sequence, three-period, three-treatment crossover study.
Clin Ther. 2009;31(12):3009-3020.20110038
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
Simard C, Michaud V, Gibbs B, et al. Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone.
Xenobiotica. 2004;34(11-12):1013-1023.15801545
Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events.
N Engl J Med. 2009;360(4):363-375.19106083
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
Soderberg Lofdal KC, Andersson ML, Gustafsson LL. Cytochrome p450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications.
Drugs. 2013;73(6):533-543.23605691
Sohonos (palovarotene) [product monograph]. Mississauga, ON, Canada: Ipsen Biopharmaceuticals Canada Inc.; January 2022.
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
Sprycel (dasatinib) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; November 2017.
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; August 2018.
Stivarga (regorafenib) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; June 2020.
Stott C, White L, Wright S, Wilbraham D, Guy G. A phase I, open-label, randomized, crossover study in three parallel groups to evaluate the effect of rifampicin, ketoconazole, and omeprazole on the pharmacokinetics of THC/CBD oromucosal spray in healthy volunteers.
Springerplus. 2013;2(1):236.23750331
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
Sunvepra (asunaprevir) [product monograph]. Montreal, Canada: Bristol-Myers Squibb Canada; March 2016.
Supect (radotinib) capsules [KR prescribing information]. http://drug.mfds.go.kr/html/bxsSearchDrugProduct.jsp?item_Seq=201200121. Accessed September 1, 2014.
Suri A, Forbes WP, Bramer SL. Effects of CYP3A inhibition on the metabolism of cilostazol.
Clin Pharmacokinet. 1999;37(suppl 2):61-68.10702888
Symdeko (tezacaftor and ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Inc; June 2019.
Symproic (naldemedine) [prescribing information]. Florham Park, NJ: Shionogi Inc; March 2017.
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
Tanaka S, Uchida S, Miyakawa S, et al. Comparison of inhibitory duration of grapefruit juice on organic anion-transporting polypeptide and cytochrome P450 3A4.
Biol Pharm Bull. 2013;36(12):1936-1941.24292052
Taniguchi K, Ohtani H, Ikemoto T, Miki A, Hori S, Sawada Y. Possible case of potentiation of the antiplatelet effect of cilostazol by grapefruit juice.
J Clin Pharm Ther. 2007;32(5):457-459.17875111
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
Tarceva (erlotinib) [prescribing information]. Northbrook, IL: OSI Pharmaceuticals, LLC; October 2016.
Tarpeyo (budesonide) delayed release capsules [prescribing information]. Stockholm, Sweden: Calliditas Therapeutics AB; December 2021.
Tasigna (nilotinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; July 2018.
Tassaneeyakul W, Guo LQ, Fukuda K, Ohta T, Yamazoe Y. Inhibition selectivity of grapefruit juice components on human cytochromes P450.
Arch Biochem Biophys. 2000;378(2):356-363.10860553
Taysofy (ethinyl estradiol and norethindrone) [prescribing information]. Bridgewater, NJ: Amneal Pharmaceuticals LLC; May 2021.
Tekturna (aliskiren) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; August 2010.
Terbinafine [prescribing information]. Peachtree City, GA: Exelan Pharmaceuticals Inc; April 2012.
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
Thomas AR, Chan LN, Bauman JL, Olopade CO. Prolongation of the QT interval related to cisapride-diltiazem interaction.
Pharmacotherapy. 1998;18(2):381-385.9545159
Tibsovo (ivosidenib) [prescribing information]. Cambridge, MA: Agios Pharmaceuticals Inc; July 2018.
Tikosyn (dofetilide) [prescribing information]. New York, NY: Pfizer Inc, February 2011.
Torisel (temsirolimus) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals Inc; March 2018.
Trikafta (elexacaftor, tezacaftor, and ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; October 2019.
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
Troost J, Tatami S, Tsuda Y, et al. Effects of strong CYP2D6 and 3A4 inhibitors, paroxetine and ketoconazole, on the pharmacokinetics and cardiovascular safety of tamsulosin.
Br J Clin Pharmacol. 2011;72(2):247-256.21496064
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
Turalio (pexidartinib) [prescribing information]. Basking Ridge, NJ: Daiichi Sankyo, Inc.; August 2019.
Tykerb (lapatinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; December 2018.
Uceris (budesonide) extended release tablets [prescribing information]. San Diego, CA: Santarus Inc; January 2013.
Uceris (budesonide) rectal foam [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals; April 2020.
Udenafil 100/200 mg tablets [KR prescribing information]. http://drug.mfds.go.kr/html/bxsSearchDrugProduct.jsp?item_Seq=20050025. Accessed September 22, 2014.
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
Uno T, Ohkubo T, Motomura S, Sugawara K. Effect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects.
Br J Clin Pharmacol. 2006;61(5):533-537.16669846
Uno T, Ohkubo T, Sugawara K, Higashiyama A, Motomura S, Ishizaki T. Effects of grapefruit juice on the stereoselective disposition of nicardipine in humans: evidence for dominant presystemic elimination at the gut site.
Eur J Clin Pharmacol. 2000;56(9-10):643-649.11214770
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, van Boxtel CJ. 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, Rutten JP, van Boxtel CJ. 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 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
Vaxar (lacidipine) [KR prescribing information]. http://drug.mfds.go.kr/html/bxsSearchDrugProduct.jsp?item_Seq=200511002. Accessed August 19, 2014.
Veilleux O, Lee TC, McDonald EG. Rebound adrenal insufficiency after withdrawal of ritonavir in a 65-year-old man using inhaled budesonide.
CMAJ. 2017;189(37):E1188-E1191.28923796
Venclexta (venetoclax) [prescribing information]. North Chicago, IL: AbbVie Inc; April 2016.
Verzenio (abemaciclib) [prescribing information]. Indianapolis, IN: Lilly USA LLC; August 2018.
Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) [prescribing information]. North Chicago, IL: AbbVie Inc.; June 2016.
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
Vitrakvi (larotrectinib) [prescribing information]. Stamford, CT: Loxo Oncology, Inc.; November 2018.
Votrient (pazopanib) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; October 2009.
Walker DK, Alabaster CT, Congrave GS, et al. Significance of Metabolism in the Disposition and Action of the Antidysrhythmic Drug, Dofetilide. In Vitro Studies and Correlation With In Vivo Data.
Drug Metab Dispos, 1996;24(4):447-455.8801060
Walsh SL, Heilig M, Nuzzo PA, Henderson P, Lofwall MR. Effects of the NK1 antagonist, aprepitant, on response to oral and intranasal oxycodone in prescription opioid abusers.
Addict Biol. 2013;18(2):332-343.22260216
Ward BA, Morocho A, Kandil A, et al. Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro.
Br J Clin Pharmacol. 2004;58(3):277-287.15327587
Wason S, DiGiancinto JL, Davis MW. Effects of grapefruit juice and Seville orange juice on the pharmacokinetic properties of colchicine in healthy subjects.
Clin Ther. 2012;34(10):2161-2173.22940371
Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes.
Life Sci. 2007;80(15):1415-1419.17303175
Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability?
Contraception. 1996;53(1):41-47.8631189
Xalkori (crizotinib) [prescribing information]. New York, NY: Pfizer Inc, September 2021.
Xarelto (rivaroxaban) [product monograph]. Toronto, Canada: Bayer; September 2008.
Xelenta (lefamulin) [prescribing information]. Ireland: Nabriva Therapeutics US, Inc.; August 2019.
Yasui N, Kondo T, Furukori H, et al. Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam.
Psychopharmacology (Berl). 2000;150(2):185-190.10907671
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.
Yeoh SW. Iatrogenic cushing syndrome from interaction between ritonavir and oral budesonide during direct acting hepatitis C therapy.
J Clin Exp Hepatol. 2016;6(3):246-249.27746623
Yin OQ, Gallagher N, Li A, Zhou W, Harrell R, Schran H. Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants.
J Clin Pharmacol. 2010;50(2):188-194.19948946
Yoganathan K, David L, Williams C, Jones K. Cushing's syndrome with adrenal suppression induced by inhaled budesonide due to a ritonavir drug interaction in a woman with HIV infection.
Int J STD AIDS. 2012;23(7):520-521.22844010
Yoshizato T, Kotegawa T, Imai H, et al. Itraconazole and domperidone: a placebo-controlled drug interaction study.
Eur J Clin Pharmacol. 2012;68(9):1287-1294.22418831
Yu Y, Loi CM, Hoffman J, Wang D. Physiologically based pharmacokinetic modeling of palbociclib.
J Clin Pharmacol. 2017;57(2):173-184.27402157
Zahir H, Greenberg J, Shuster D, Hsu C, Watanabe K, LaCreta F. Evaluation of absorption and metabolism-based DDI potential of pexidartinib in healthy subjects.
Clin Pharmacokinet. 2022;61(11):1623-1639. doi:10.1007/s40262-022-01172-936264536
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; February 2015.
Zocor (simvastatin) [prescribing information]. Whitehouse Station, NJ: Merck & Co., Inc.; September 2020.
Zohydro ER (hydrocodone bitartrate) [prescribing information]. San Diego, CA: Zogenix Inc; August 2014.
Zortress (everolimus) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; March 2010.
Zykadia (ceritinib) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; March 2019.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.