Pharmacological Effects of Grapefruit Juice with Medications

Pharmacological Effects of Grapefruit Juice With Medications

PHARMACOLOGICAL EFFECTS OF GRAPEFRUIT JUICE WITH MEDICATIONS
Grapefruit or grapefruit juice has been shown to affect the metabolism of many medications, increasing the risk of toxicity and adverse events. Characteristics of oral medications that may interact with grapefruit include extensive metabolism through the intestinal cytochrome P450 3A4 (CYP3A4) system, low bioavailability, and a narrow therapeutic index. Grapefruit juice interacts through the intestinal CYP3A4 system and can inhibit the concentration for 24–72hrs. Not an exclusive list of medications that may interact with grapefruit. Caution should be taken by both patient and physician and monitor adverse reactions when taking medications that may interact with grapefruit or juice.
Generic	Brand	Clinical Implications of Co‑administration with Grapefruit or Grapefruit Juice
ANTI-INFECTIVES
erythromycin	Ery-Tab, Eryped, E.E.S.	Inhibits CYP3A4-mediated metabolism resulting in increased erythromycin bioavailability.
maraviroc	Selzentry	May increase plasma concentrations of maraviroc and should be avoided.
praziquantel	Biltricide	1.6-fold increase in the C_max and a 1.9-fold increase in the AUC of praziquantel. The effect of this increase on the efficacy and safety of praziquantel has not been systemically evaluated.
primaquine phosphate	Primaquine	Increases bioavailability of primaquine resulting in increased adverse effects. Avoid co-administration.
rilpivirine	Edurant	May increase plasma concentrations of rilpivirine and should be avoided.
CARDIOVASCULAR AGENTS
amiodarone	—	Inhibits CYP3A4-mediated metabolism of oral amiodarone resulting in increase plasma levels of amiodarone. Avoid co‑administration.
apixaban	Eliquis	May moderately inhibit CYP3A4-mediated metabolism of apixaban. If co-administration is necessary, use with caution.
atorvastatin	Lipitor	Inhibits CYP3A4 and can increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption (>1.2L/day).
clopidogrel	Plavix	May impair the efficacy of clopidogrel. Avoid co-administration.
dofetilide	Tikosyn	Inhibitor of the CYP3A4 isoenzyme, thus could increase systemic dofetilide exposure. If co-administration is necessary, use with caution.
dronedarone	Multaq	Moderate inhibitor of CYP3A, results in a 3-fold increase in dronedarone exposure and a 2.5-fold increase in C_max. Avoid co-administration.
eplerenone	Inspra	May increase plasma concentrations of eplerenone resulting in hyperkalemia and serious arrhythmias.
felodipine	—	2-fold increase in felodipine AUC and C_max with no prolongation of half-life. Avoid co-administration prior to and during treatment.
lovastatin	—	Inhibits CYP3A4 and can increase plasma concentrations of lovastatin. Avoid co-administration.
nifedipine	Procardia	2-fold increase in nifedipine AUC and C_max with no change in half-life. Avoid co-administration.
nisoldipine	Sular	3-fold increase in nisoldipine C_max and 2-fold increase in nisoldipine AUC. Avoid co-administration.
simvastatin	Zocor	Inhibits CYP3A4 and can increase plasma concentrations of simvastatin and may increase risk of myopathy. Avoid co-administration.
verapamil	Verelan	May significantly increase concentrations of verapamil. Increased S-and R-verapamil AUC0-12 by 36% and 28%, respectively. Steady state C_max and C_min of S-verapamil increased by 57% and 16.7%, respectively compared to control. C_max and C_min of R-verapamil increased by 40% and 13%, respectively. No clinical consequences expected.
ticagrelor	Brilinta	Increases ticagrelor exposure by more than 2-fold, resulting to an enhanced and prolonged antiplatelet effect.
IMMUNOSUPRESSANTS
cyclosporine	Neoral	Affects metabolism and increases blood concentrations of cyclosporine. Avoid co-administration.
everolimus	Zortress	Inhibits CYP3A4 and P-gp activity and should therefore be avoided.
sirolimus	Rapamune	Reduces CYP3A4-mediated drug metabolism and must not be taken with or used for dilution of sirolimus.
tacrolimus	Prograf	Inhibits CYP3A-mediated metabolism resulting in increased tacrolimus whole blood trough concentrations. Avoid co-administration.
ONCOLOGY AGENTS
axitinib	Inlyta	May increase plasma concentrations of axitinib and should be avoided.
crizotinib	Xalkori	May increase plasma concentrations of crizotinib and should be avoided.
dasatinib	Sprycel	May increase plasma concentrations of dasatinib and should be avoided.
erlotinib	Tarceva	May increase plasma concentrations of erlotinib and should be avoided.
everolimus	Afinitor	May increase exposures of everolimus and should be avoided.
lapatanib	Tykerb	May increase plasma concentrations of lapatinib and should be avoided.
nilotinib	Tasigna	May increase plasma concentrations of nilotinib and should be avoided.
pazopanib	Votrient	May increase plasma concentrations of pazopanib and should be avoided.
ruxolitinib	Jakafi	The recommended starting dose of ruxolitinib is 10mg twice daily for patients with a platelet count ≥100 × 10⁹/L. Concurrent administration of ruxolitinib should be avoided in patients with platelet counts <100 × 10⁹/L.
sunitinib	Sutent	May increase plasma concentrations of sunitinib and should be avoided.
vandetanib	Caprelsa	May increase plasma concentrations of vandetanib and should be avoided.
vemurafenib	Zelboraf	May increase plasma concentrations of vemurafenib and should be avoided.
PAIN MEDICATIONS
dihydroergotamine mesylate	—	A potential risk for serious toxicity (including vasospasm) exists.
ergotamine tartrate + caffeine	—	A potential risk for serious toxicity (including vasospasm) exists.
fentanyl (oral)	Fentora	May result in a potentially dangerous increase in plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.
oxycodone	Oxycontin	May result in a potentially dangerous increase in plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.
PSYCHOTROPIC AGENTS
buspirone	—	4.3 fold increase in C_max; 9.2 fold increase in AUC. Avoid drinking large amounts (200mL double-strength 3 times daily) of grapefruit juice.
lurasidone	Latuda	May increase plasma concentrations of lurasidone resulting in increased adverse effects.
pimozide	—	Inhibits CYP3A4-mediated metabolism of pimozide. Avoid co-administration.
quetiapine	Seroquel	May increase plasma concentrations of quetiapine resulting in increased adverse effects.
triazolam	Halcion	Increases the C_max of triazolam by 25%, increases AUC by 48%, and increases half-life by 18%. Avoid co-administration.
ziprasidone	Geodon	May increase plasma concentrations of ziprasidone resulting in increased adverse effects.
UROLOGIC AGENTS
tadalafil	Cialis	Likely increases of tadalafil exposure.
vardenafil	—	Increased systemic concentration of vardenafil. Avoid co-administration.
OTHERS
budesonide	Entocort EC	After extensive intake of grapefruit juice, the systemic exposure for oral budesonide increased about 2 times. Ingestion of grapefruit or grapefruit juice should be avoided.
cilostazol	—	Increase in the C_max of cilostazol by ~ 50%, but has no effect on AUC. Avoid or reduce dose to 50mg with co-administration.
colchicine	Colcrys	Increases the risk of colchicine-induced toxic effects; significant increase in colchicine plasma concentration is anticipated. Grapefruit and grapefruit juice should not be consumed during colchicine treatment.
dextromethorphan	Robitussin	Increases bioavailability of dextromethorphan resulting in increased adverse effects.
fexofenadine	Allegra	May reduce bioavailability and exposure of fexofenadine. In a bioequivalence study, the bioavailability of fexofenadine was reduced by 36%. Take with water.
ivacaftor	Kalydeco	Co-administration may increase exposure of ivacaftor. Grapefruit or Seville oranges should be avoided during treatment.
tolvaptan	Samsca	Co-administration results in a 1.8-fold increase in exposure to tolvaptan.
REFERENCES
Bailey DG, Dresser G, Arnold JMO. Grapefruit–medication interactions: Forbidden fruit or avoidable consequences? CMAJ. 2013 March 05; 185(4): 309-316. doi: https://doi.org/10.1503/cmaj.120951. Stump AL, Mayo T, Blum A. Management of Grapefruit-Drug Interactions. Am Fam Physician. 2006 Aug 15; 74(4): 605-608. (Rev. 2/2023)

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