User:Kloub

'The Effect of Grapefruit Juice on Drug'''

by Dr. Osama Kloub
' The list of drugs is not exhaustive. As more drugs in combination with grapefruit juice are studied, the list of interactions may change

Grapefruit Juice Effect • Repeated doses of grapefruit juice markedly increase amiodarone levels. • Evaluated in controlled studies in healthy volunteers; increased AUC and Cmax

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for adverse effects associated with increased serum levels of amiodarone (e.g., bradycardia, elevation of liver enzymes).

Atorvastatin:

Grapefruit Juice Effect • Grapefruit juice may increase plasma levels of HMG CoA reductase inhibitors m.etabolized by CYP 3A4. • Atorvastatin appears to be affected to a lesser extent than lovastatin and simvastatin.

Management • Avoid consumption of grapefruit juice; other juices not known to interact. • Consider choosing a HMG CoA reductase inhibitor not m.etabolized by CYP 3A4 (e.g., pravastatin and fluvastatin). • If used in combination, monitor for adverse effects associated with increased serum levels of atorvastatin (e.g., myopathy, rhabdomyolysis).

Benzodiazepines, see diazepam, triazolam

Budesonide

Grapefruit Juice Effect • Substantial intake of grapefruit juice may increase systemic exposure to orally administered budesonide. • The bioavailability of orally administered budesonide was approximately doubled in male subjects taking 600 mL of concentrated grapefruit juice per day for 4 days.

Management • Avoid consumption of grapefruit juice; other juices not known to interact. • If used in combination, monitor for adverse effects associated with the use of glucocorticoids (e.g., hyperglycemia, Cushingoid features).

Buspirone:

Grapefruit Juice Effect • Repeated doses of grapefruit juice markedly increase buspirone serum concentration.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for adverse effects associated with increased serum levels of buspirone (e.g., sedation and psychomotor impairment).

Calcium Channel Blockers, see felodipine, nifedipine, nimodipine

Carbamazepine:

Grapefruit Juice Effect • May increase carbamazepine serum levels. • Evaluated in small controlled study of epileptic patients; increased AUC, peak and trough concentrations

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for signs of carbamazepine toxicity (e.g., drowsiness, dizziness, headache, unsteadiness on the feet, diplopia, nausea, vomiting).

Carvedilol:

Grapefruit Juice Effect • Can result in higher plasma levels of carvedilol due to reduced drug m.etabolism. • Evaluated in controlled studies; increased area under curve (AUC).

Management • Evidence of this interaction is limited. • If used in combination, monitor for adverse effects associated with increased serum levels of carvedilol (e.g., low blood pressure and bradycardia).

Clomipramine:

Grapefruit Juice Effect • May increase clomipramine serum levels. • The interaction between grapefruit juice and other tricyclic antidepressants has not been established.

Management • Avoid consumption of grapefruit juice; other juices not known to interact. • If used in combination, monitor for adverse effects associated with increased serum levels of clomipramine (e.g., drowsiness, hypotension, respiratory depression, cardiovascular disturbances, anticholinergic effects, agitation).

Cyclosporine:

Grapefruit Juice Effect • May increase plasma levels of cyclosporine. • Evaluated in controlled studies; increased AUC and increased plasma concentration.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for symptoms of toxicity (e.g., nephrotoxicity, hepatotoxicity, increased immunosuppression). • Monitor cyclosporine effect particularly when grapefruit juice is initiated, discontinued or the interval between drug and grapefruit juice ingestion changes. • Lower doses of cyclosporine may be required.

Diazepam:

Grapefruit Juice Effect • May increase diazepam levels. • Evaluated in controlled studies in healthy volunteers; increased AUC and Cmax.

Management • Clinical importance is unknown. • It is likely that some patients would be adversely affected especially those in whom diazepam levels are likely to be elevated (e.g., older individuals, those with liver impairment or concurrent use of other cytochrome P450-inhibitors). • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for increased sedation.

Erythromycin:

Grapefruit Juice Effect • Grapefruit juice may increase serum concentrations of erythromycin. • Evaluated in an open crossover study in six healthy subjects; increased Cmax and AUC.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for adverse effects that may be associated with erythromycin.

Ethinyl Estradiol:

Grapefruit Juice Effect • Appears to increase serum concentrations of ethinyl estradiol. • Theoretically, grapefruit juice may affect the m.etabolism of other estrogens.

Management • Clinical significance is not established. • Avoid consumption of grapefruit juice; other juices not known to interact. • If used in combination, suggest maintaining a consistent interval between drug and grapefruit juice ingestion when possible.

Felodipine:

Grapefruit Juice Effect • Can increase plasma levels and intensify the clinical effects of some 1,4-dihydropyridine calcium channel blockers. • Can significantly increase plasma felodipine levels. • May be affected to a greater extent than other dihydropyridine calcium channel blockers.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for adverse effects associated with increased serum concentrations of felodipine (e.g., decreased diastolic blood pressure, increased heart rate, flushing, headache and lightheadedness).

HMG CoA reductase inhibitors, see atorvastatin, lovastatin, simvastatin

Itraconazole:

Grapefruit Juice Effect • May decrease itraconazole serum levels. • Evaluated in controlled study in healthy volunteers; decreased AUC and Cmax. This effect has not been consistently shown in all studies. • May occur with ketoconazole but no data exists.

Management • Avoid consumption of grapefruit juice. • If used in combination, monitor patient for loss of efficacy.

Lovastatin:

Grapefruit Juice Effect • Repeated doses may result in increased lovastatin serum concentrations. • Simvastatin appears to be similarly affected by grapefruit juice; however, atorvastatin is not as greatly affected.

Management • Avoid consumption of grapefruit juice; other juices not known to interact. • Consider choosing a HMG CoA reductase inhibitor not m.etabolized by CYP 3A4 (e.g., fluvastatin and pravastatin). • If used in combination, monitor for signs of adverse effects associated with increased serum concentrations of lovastatin (e.g., myopathy, rhabdomyolysis).

Methylprednisolone:

Grapefruit Juice Effect • Grapefruit juice may increase serum concentrations and half-life of methylprednisolone. • Evaluated in a crossover study in ten healthy subjects; repeated administration of double-strength grapefruit juice increased AUC, Cmax and half-life of methylprednisolone. Clinical significance unknown. The effect on half-life shown in this study is likely a function of the large doses of grapefruit juice administered.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for adverse effects that may be associated with the use of corticosteroids (e.g., hyperglycemia, Cushingoid features).

Nifedipine:

Grapefruit Juice Effect • May lead to increased serum levels of nifedipine. • Evaluated in single dose controlled studies in healthy volunteers.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for signs of adverse effects associated with increased serum concentrations of nifedipine (e.g., decreased diastolic blood pressure, increased heart rate, flushing, headache and lightheadedness).

Nimodipine:

Grapefruit Juice Effect • May increase plasma concentrations of nimodipine. • Pharmacokinetics after a single dose of grapefruit juice are altered. • Pharmacodynamic effects may be augmented.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for increased hypotensive effect and side effects such as headache.

Pimozide:

Grapefruit Juice Effect • Can result in elevated levels due to decreased drug m.etabolism. • Elevated levels may enhance the risk of QT prolongation.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for signs of adverse effects associated with increased serum levels of pimozide (e.g., torsades de pointes, extrapyramidal symptoms, hypotension).

Protease inhibitors, see saquinavir

Saquinavir:

Grapefruit Juice Effect • Can increase absorption of saquinivir from hard gel capsules. Effect on soft gel capsules unknown, but may differ due to intrinsically better absorption from this formulation. • A decrease in AUC has been reported with indinavir; effect on ritonavir has not been studied.

Management • Clinical significance is unknown.

Sertraline:

Grapefruit Juice Effect • Grapefruit juice may increase serum concentrations of sertraline. • Evaluated in an open controlled study in five patients being treated for depression with 50-75 mg/day of sertraline; increased the mean trough concentration of sertraline. No subject was withdrawn from the study due to adverse effects or mood changes. Clinical significance unknown.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for adverse effects associated with increased serum levels of sertraline (e.g., insomnia or somnolence, tremor, dizziness).

Simvastatin:

Grapefruit Juice Effect • May increase simvastatin serum concentrations. • Lovastatin bioavailability is similarly increased by grapefruit juice; however, atorvastatin is not as greatly affected.

Management • Avoid consumption of grapefruit juice; other juices not known to interact. • Consider choosing a HMG CoA reductase inhibitor not m.etabolized by CYP 3A4 (e.g., fluvastatin and pravastatin). • If used in combination, monitor for signs of adverse effects associated with increased serum concentrations of simvastatin (e.g., myopathy, rhabdomyolysis).

Sirolimus:

Grapefruit Juice Effect • Grapefruit juice may have the potential to increase sirolimus blood concentrations

Management • Avoid grapefruit juice; the manufacturer of Rapamune® specifically recommends taking Rapamune® with either water or orange juice. • If used in combination, monitor for increased blood concentrations and for adverse effects associated with increased serum concentrations of sirolimus (e.g., thrombocytopenia, hyperlipidemia)

Tacrolimus:

Grapefruit Juice Effect • May have the potential to increase tacrolimus blood concentrations.

Management • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for increased blood levels and symptoms of toxicity (e.g., nephrotoxicity, hepatotoxicity, increased immunosuppression).

Triazolam:

Grapefruit Juice Effect • May increase triazolam serum levels. • Evaluated in controlled studies in healthy volunteers; increased AUC and Cmax and small increase in psychomotor impairment.

Management • It is likely that some patients would be adversely affected especially those in whom triazolam levels are likely to be elevated (e.g., older individuals, those with liver impairment or concurrent use of other cytochrome P450-inhibitors). • Avoid grapefruit juice; other juices not known to interact. • If used in combination, monitor for increased sedation. Significant increase in drowsiness has been reported