PHARMACOLOGICAL EFFECTS OF COMMON MEDICATIONS WITH GRAPEFRUIT JUICE

PHARMACOLOGICAL EFFECTS OF COMMON MEDICATIONS WITH GRAPEFRUIT JUICE
Grapefruit is a healthy addition to a well-balanced diet. However, the fruit or 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 24–72 hours.1 This list is based on manufacturer's prescribing information and is not a complete 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.
Brand	Generic	Clinical Implications of Co-administration with Grapefruit or Grapefruit Juice
ANTIARRHYTHMICS
Cordarone	amiodarone	Inhibits CYP3A4-mediated metabolism of oral amiodarone resulting in increase plasma levels of amiodarone. Avoid co-administration.
Multaq	dronedarone	Moderate inhibitor of CYP3A, results in a 3-fold increase in dronedarone exposure and a 2.5-fold increase in Cmax. Avoid co-administration.
Ranexa	ranolazine	Moderate CYP3A inhibitor. Limit dose of Ranexa to 500mg twice daily.
Tikosyn	dofetilide	Inhibitor of the CYP3A4 isoenzyme, thus could increase systemic dofetilide exposure. If co-administration is necessary, use with caution.
ANTIMALARIAL
Coartem	artemether/lumefantrine	May increase concentrations of artemether and/or lumefantrine and potentiate QT prolongation.
ANTIPSYCHOTIC
Orap	pimozide	Inhibits CYP3A4-mediated metabolism of pimozide. Avoid co-administration.
CALCIUM CHANNEL BLOCKERS
Nimotop	nimodipine	Elevates plasma concentrations and prolongs action of nimodipine due to a decreased first pass metabolism or reduced clearance. Avoid co-administration.
Plendil	felodipine	2-fold increase in felodipine AUC and Cmax. Avoid co-administration prior to and during treatment.
Procardia	nifedipine	2-fold increase in nifedipine AUC and Cmax with no change in half-life. Avoid co-administration.
Sular	nisoldipine	3-fold increase in nisoldipine Cmax and 2-fold increase in nisoldipine AUC. Avoid co-administration before and after dosing.
CHOLESTEROL-LOWERING MEDICATIONS
Lipitor	atorvastatin	Inhibits CYP3A4 and can increase plasma concentrations of atorvastatin, especially with excessive grapefruit juice consumption (>1.2 liters per day).
Mevacor	lovastatin	Inhibits CYP3A4 and can increase plasma concentrations of lovastatin. Avoid large quantities of grapefruit juice (>1 quart daily).
Zocor	simvastatin	Inhibits CYP3A4 and can increase plasma concentrations of simvastatin and may increase risk of myopathy. Avoid large quantities of grapefruit juice (>1 quart daily).
H1-RECEPTOR ANTAGONIST
Allegra	fexofenadine	May reduce bioavailability and exposure of fexofenadine. In a bioequivalence study, the bioavailability of fexofenadine was reduced by 36%. Take with water.
IMMUNOSUPPRESSANTS
Neoral	cyclosporine	Affects metabolism and increases blood concentrations of cyclosporine. Avoid co-administration.
Prograf	tacrolimus	Affects CYP3A-mediated metabolism and should be avoided.
Torisel	temsirolimus	May increase plasma concentrations of sirolimus, a major metabolite of temsirolimus, and should be avoided.
INTERMITTENT CLAUDICATION THERAPY
Pletal	cilostazol	Increase in the Cmax of cilostazol by ∼50%, but has no effect on AUC.
KINASE INHIBITORS
Gleevec	imatinib	May increase plasma concentrations of imatinib and should be avoided.
Sprycel	dasatinib	May increase plasma concentrations of dasatinib and should be avoided.
Sutent	sunitinib	May increase plasma concentrations of sunitinib and should be avoided.
Tarceva	erlotinib	Dose reduction in 50mg decrements should be considered if severe adverse reactions occur. Use with caution.
Tasigna	nilotinib	May increase plasma concentrations of nilotinib and should be avoided.
PSYCHOTROPIC AGENTS
BuSpar	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.
Halcion	triazolam	Increases the Cmax of triazolam by 25%, increases AUC by 48%, and increases half-life by 18%. Use with caution.
Tegretol	carbamazepine	Inhibits carbamazepine metabolism and may increase plasma carbamazepine levels. Use with caution.
Versed	midazolam	Caution is advised when midazolam is administered concomitantly with drugs that are known to inhibit the P450-3A4 enzyme system