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. Charac-
teristics 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
ALKALOID
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.
ANTIARRHYTHMICS
amiodarone Cordarone Inhibits CYP3A4-mediated metabolism of oral amiodarone resulting in increase plasma levels of amiodarone. 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 Cmax. Avoid co‑administration.
ANTIHELMINTHIC
praziquantel Biltricide 1.6-fold increase in the Cmax and a 1.9‑fold increase in the AUC of praziquantel.
ANTIPSYCHOTIC
pimozide Orap Inhibits CYP3A4-mediated metabolism of pimozide. Avoid co‑administration.
CALCIUM CHANNEL BLOCKERS
felodipine Plendil 2-fold increase in felodipine AUC and Cmax. Avoid co‑administration prior to and during treatment.
nifedipine Procardia 2-fold increase in nifedipine AUC and Cmax with no change in half‑life. Avoid co‑administration.
nisoldipine Sular 3-fold increase in nisoldipine Cmax and 2‑fold increase in nisoldipine AUC. Avoid co‑administration before and after dosing.
verapamil Verelan May significantly increase concentrations of verapamil. Increased S- and R‑verapamil AUC0−12 by 36% and 28%, respectively. Steady state Cmax and Cmin of S‑verapamil increased by 57% and 16.7%, respectively compared to control. Cmax and Cmin of R‑verapamil increased by 40% and 13%, respectively.
CHOLESTEROL-LOWERING MEDICATIONS
atorvastatin Lipitor Inhibits CYP3A4 and can increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption (>1.2L/day).
lovastatin Inhibits CYP3A4 and can increase plasma concentrations of lovastatin. Avoid large quantities of grapefruit juice (>1 quart daily).
simvastatin Zocor Inhibits CYP3A4 and can increase plasma concentrations of simvastatin and may increase risk of myopathy. Avoid large quantities of grapefruit juice (>1 quart daily).
CYSTIC FIBROSIS THERAPY
ivacaftor Kalydeco Co-administration may increase exposure of ivacaftor. Grapefruit or Seville oranges should be avoided during treatment.
ERGOT ALKALOIDS
dihydroergo-
tamine mesylate
D.H.E. 45 A potential risk for serious toxicity (including vasospasm) exists.
ergotamine 
tartrate + caffeine
A potential risk for serious toxicity (including vasospasm) exists.
H1-RECEPTOR ANTAGONIST
fexofenadine Allegra May reduce bioavailability and exposure of fexofenadine. In a bioequivalence study, the bioavailability of fexofenadine was reduced by 36%. Take with water.
HYPONATREMIA THERAPY
tolvaptan Samsca Co-administration results in a 1.8‑fold increase in exposure to tolvaptan.
IMMUNOSUPPRESSANTS
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 with concomitant use of everolimus and cyclosporine.
sirolimus Rapamune Reduces CYP3A4-mediated drug metabolism and must not be taken with or used for dilution of sirolimus.
tacrolimus Prograf Affects CYP3A-mediated metabolism and should be avoided.
temsirolimus Torisel May increase plasma concentrations of sirolimus, a major metabolite of temsirolimus, and should be avoided.
INTERMITTENT CLAUDICATION THERAPY
cilostazol Pletal Increase in the Cmax of cilostazol by ∼50%, but has no effect on AUC.
MYELOFIBROSIS THERAPY
ruxolitinib Jakafi The recommended starting dose of ruloxitinib is 10mg twice daily for patients with a platelet count ≥100 × 109/L. Concurrent administration of should be avoided in patients with platelet counts <100 × 109/L.
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.
everolimus Afinitor May increase exposures of everolimus and should be avoided.
ixabepilone Ixempra May increase plasma concentrations of ixabepilone 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.
sunitinib Sutent May increase plasma concentrations of sunitinib and should be avoided.
OPIOID
fentanyl Fentora May result in a potentially dangerous increase in fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.
PHOSPHODIESTERASE TYPE 5 INHIBITORS
tadalafil Cialis Likely increase of tadalafil exposure.
vardenafil Staxyn Do not use, as the systemic concentration of vardenafil is increased.
PSYCHOTROPIC AGENTS
buspirone 4.3 fold increase in Cmax; 9.2 fold increase in AUC. Avoid drinking large amounts (200mL double-strength three times daily) of grapefruit juice.
triazolam Halcion Increases the Cmax of triazolam by 25%, increases AUC by 48%, and increases half-life by 18%. Use with caution.
STEROID
budesonide Entocort 
EC
After extensive intake of grapefruit juice, the systemic exposure for oral budesonide increased about two times. Ingestion of grapefruit or grapefruit juice should be avoided.
REFERENCES

Stump AL, Mayo T, Blum A. Management of Grapefruit-Drug Interactions. Am Fam Physician. 2006 Aug 15;74(4):605–608.

(Rev. 9/2013)

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