Where to get grapefruit juice

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The City field is Required. The State field is Required. The Zip Code field is Required. The Zip Code is not in a correct format. Sign in to the Cranberry Club. Sign In Forgot Password? Omission of any of the components resulted in decreased potency, suggesting that all major furanocoumarins contribute to the inhibitory effects of grapefruit juice [ 40 ]. However, others have suggested that DHB and Bergamottin are not the primary substances responsible for inhibition of CYP activity clinically [ 41 , 42 ].

For now, this topic also remains a subject of intense research. Since the effects of grapefruit juice were first noticed with felodipine, this class of drugs has been intensively studied with grapefruit juice. The degree to which the intestinal CYP system metabolizes this class of drugs and affects their oral bioavailability varies markedly. In a study done by Lundahl J et al. However, this study also found out that the intravenous pharmacokinetics of felodipine were not significantly altered with grapefruit juice.

The main acute effect of the grapefruit juice on the plasma concentrations of felodipine was believed to be mediated by inhibition of gut wall metabolism. Grapefruit juice-felodipine interaction increases with increasing frequency and amount of grapefruit juice ingestion, hence it has been determined that an interval of 2—3 days between grapefruit juice intake and felodipine administration is necessary if the interaction is to be avoided [ 44 ].

Blood pressure responses to felodipine with grapefruit juice have also been assessed in the elderly and the systolic and diastolic blood pressures were found to be lower with grapefruit juice in the single-dose state, whereas they were not different between treatments in the steady-state dose [ 45 ].

The different blood pressure results between the studies can be explained by felodipine concentration-blood pressure response relationships. The elderly should be particularly cautioned about concomitant grapefruit juice and felodipine ingestion. In the benzothiazepine calcium channel antagonists group, diltiazem has been found to have an increased bioavailability on co administration of a single intake of grapefruit juice.

However in contrast to this, another study showed the bioavailability to be unchanged with grapefruit juice suggesting that factors other than biotransformation may be contributing [ 47 ]. Compared with water, grapefruit juice increased the maximum concentration of nisoldipine and reduced the time to reach maximum nisoldipine concentration [ 48 ]. However, the effects of grapefruit pulp intake were smaller than those produced by grapefruit juice intake, indicating that grapefruit pulp and juice have different effects on the pharmacokinetics [ 49 ].

A clinical study was performed to see the duration of this interaction in the body. Eight healthy volunteers were given grapefruit juice at 14, 38, 72 and 96 hours. Compared with the control group, the maximum plasma concentration of nisoldipine was significantly increased after grapefruit juice intake in at 0 and 14 hours, and the plasma concentration was significantly increased at each time till 72 hours [ 50 ].

It is therefore necessary to withhold grapefruit juice for at least 3 days before administration of the drug to prevent grapefruit juice -nisoldipine interaction. Regarding verapamil, there are conflicting reports about its interaction with grapefruit juice. One study showed an increase in its bioavailability at steady state [ 51 ] while another showed no significant change in pharmacokinetics on a single administration. ACE-inhibitors like enalapril, captopril, lisinopril and ramipril have not shown any interaction with grapefruit juice although such an interaction might be possible with angiotensin II type 1 receptor antagonists like losartan and valsartan [ 18 ].

Thiazide diuretics and alph 1 adrenergic antagonists doxazosin, terazosin, prazosin have also shown no interaction with grapefruit juice [ 18 ].

On interaction with grapefruit juice, there has been shown to be complete inhibition of N-DEA production [ 52 ] leading to an overall decrease in the arrythmogenic side effects of amiodarone [ 17 ].

These results are in agreement with in vitro data pointing to the involvement of CYP3A in the metabolism of amiodarone and other Ca antagonists, suggesting that this interaction should be taken into account when prescribing this antiarrhythmic drug.

Similarly grapefruit juice has been found to increase oral nimodipine bioavailability [ 53 ]. The same cannot be said of amlodipine, on which grapefruit juice has no appreciable effect [ 54 ].

One of the possible active ingredients in commercial grapefruit juice is Bergamottin, as mentioned before.

This was determined after studying the effects of the furanocoumarin derivative on nifedipine NFP pharmacokinetics, suggesting that bergamottin in grapefruit might be the substance that elevates the NFP plasma concentrations [ 55 ].

Further studies have also been done to determine if even unprocessed grapefruit could cause drug interactions. It has been shown that unprocessed grapefruit can cause a drug interaction with felodipine [ 56 ]. With antivirals, authors concluded that concomitant administration of grapefruit juice increases gastric pH and delays indinavir absorption but does not uniformly affect the systemic bioavailability of indinavir in HIV-infected subjects [ 57 , 58 ].

Similarly grapefruit juice has been shown clinically to not significantly affect amprenavir pharmacokinetics [ 59 ]. It is suggested that this may be because the primary metabolism of these drugs is not in the small intestine. On the other hand regarding saquinavir, it has been shown that grapefruit juice increases the bioavailability of saquinavir without affecting its clearance, suggesting that inhibition of intestinal CYP3A4 may contribute [ 60 ].

And since the antiretroviral effect of saquinavir is dose-dependent, it has been suggested that inhibition of CYP3A4 may represent a way to enhance its effectiveness without increasing the dose. Amongst anti malarials, grapefruit juice significantly increases the oral bioavailability of artemether but does not prevent the time-dependent reduction in bioavailability or elimination half-life, suggesting a role for intestinal CYP3A4 in the presystemic metabolism of artemether [ 61 , 62 ].

Similar results have also been seen after a single oral dose of praziquantel with ml of grapefruit juice [ 63 ]. Quinine appears to be unaffected in its pharmacokinetics. Since quinine is a low clearance drug with a relatively high oral bioavailability, and is primarily metabolised by human liver CYP3A4, the lack of effect of grapefruit juice on quinine pharmacokinetics again supports the view that the site of CYP inhibition by grapefruit juice is mainly in the gut [ 17 , 64 ].

In antibiotics, administration of grapefruit juice increased the time to peak concentration of clarithromycin but did not affect other pharmacokinetic parameters [ 66 ] while in antiparasitics, albendazole showed an increase in bioavailability upon administration of grapefruit juice [ 67 ].

A marked interaction between oral midazolam and grapefruit juice has been found and the data is consistent again with a reduced first-pass metabolism of midazolam, resulting in increased bioavailability of midazolam [ 68 , 69 ]. The clinical importance of this is especially for patients with other causes for increased midazolam bioavailability such as advanced age, cirrhosis of the liver, and administration of other inhibitors of cytochrome P Thus, patients with liver cirrhosis are more dependent on the intestine for metabolism of CYP3A4 substrates than subjects with normal liver function.

Another important implication of this interaction is in dentistry. Oral midazolam is a frequently used sedative in pediatric dentistry. Although an oral form of midazolam is now commercially available, some practitioners continue to use the IV midazolam as an oral medication. If the injectible form of midazolam is administered orally, its bitter taste requires the use of a flavoring agent like grapefruit juice.

This results in increased blood plasma levels of midazolam causing excessive levels of sedation for the pediatric patient. Grapefruit juice therefore should be contraindicated for use with oral midazolam especially in such patients [ 70 ]. Similar results have also been seen with triazolam [ 71 ].

One study however, did show that grapefruit juice did not have any particular interaction with oral doses of 10 mg midazolam and 0. However, since more studies have determined increases in midazolam and triazolam bioavailbility, grapefruit juice should be administered with caution with these drugs.

However, alprazolam remains unaffected in pharmacokinetics or pharmacodynamics due to its high bioavailability [ 73 ]. Among antipsychotics, clozapine remained unaffected after consumption of regular-strength grapefruit juice, usually taken as mL b.

One reason for this is that enzymes other than CYP3A4 also mediate clozapine disposition. Haloperidol remains unaffected by grapefruit juice [ 75 ]. In anti convulsants, grapefruit juice increases the bioavailability of carbamazepine [ 76 ] but does not affect the pharmacokinetics of phenytoin [ 77 ].

Grapefruit juice considerably increases plasma buspirone concentrations [ 78 ] and also increases sertraline bioavailability [ 79 ]. Grapefruit juice therefore should be contraindicated during administration of buspirone and sertraline.

A number of studies have shown that a single glass of grapefruit juice produced an individual-dependent, variable increase in the systemic bioavailability of cisapride by inhibition of intestinal cytochrome P 3A4 CYP3A4 activity. The effect of grapefruit juice on racemic nitrendipine was also to increase its bioavailability and it was found that it inhibits the stereoselective metabolism of nitrendipine in humans [ 83 ].

Regarding terfenidine, the ingestion of grapefruit juice leads to its enhanced systemic bioavailability [ 84 , 85 ]. This is especially important because the raised levels of terfenidine can prolong the QT interval in the electrocardiogram sufficiently to precipitate the ventricular arrhythmia of Torsade-des-pointes [ 86 ].

Incidentally, both terfenidine and cisapride have been globally withdrawn from the market due to serious cardiac arrythmias precipitated by their interaction with other drugs if simultaneously taken. Taking simvastatin first, the active ingredient bergamottin has been shown to inhibit simvastatin SV metabolism and increase the serum concentrations of simvastatin and its active metabolite simvastatin acid, and, to a lesser extent, those of active and total HMG-CoA reductase inhibitors [ 87 , 88 ].

The probable mechanism of this interaction was also the inhibition of CYP3A4-mediated first-pass metabolism of simvastatin by grapefruit juice in the small intestine. Bergamottin BG and naringenin NRG could therefore be applied as markers in food-drug interaction studies in order to adjust posology and the dose of simvastatin should be accordingly reduced.

It was also shown that the interaction potential of even high amounts of grapefruit juice with CYP3A4 substrates dissipates within 3 to 7 days after ingestion of the last dose of grapefruit juice [ 89 ]. The grapefruit juice effect has also been studied on lovastatin. Lovastatin and its active metabolite, lovastatin acid had greatly increased serum concentrations after grapefruit juice administration [ 90 ].

However, one other study has shown a minimal effect of a glass of regular-strength grapefruit juice on plasma concentration after a 40 mg evening dose of lovastatin [ 91 ]. Although grapefruit juice also increases the AUC of atorvastatin, the actual increase in activity is fairly modest, possibly due to a simultaneous effect of decreasing the AUC of active metabolites of atorvastatin [ 17 ]. Regardless, grapefruit juice should not be concomitantly ingested with atorvastatin, lovastatin or simvastatin.

On the other hand, pravastatin, fluvastatin and rosuvastatin are three statin drugs that have been shown not to interact with grapefruit juice [ 18 ].

These may be useful alternatives in settings where there is a concern regarding potential interaction with grapefruit juice. Other cholesterol-lowering agents like nicotinic acid and common fibric acid derivatives and bile acid sequestrants have shown no interaction, and therefore may be safely used, with grapefruit juice [ 18 ]. In patients with autoimmune diseases, the effect of chronic grapefruit juice administration on steady state blood concentrations of cyclosporine and metabolites is an increase in both parent and metabolite profiles [ 92 ].

This interaction was studied in renal transplant recipients. Administration of cyclosporine with grapefruit juice compared with water induced a moderate, butsignificant increase in the systemic exposure of cyclosporine [ 93 , 94 ]. Most of these studies involving cyclosporine were done on adult patients.

Package type: Individual Item Multi-Serving. Percentage juice content 1: Net weight: 52 Ounces. Beverage container material: Plastic. TCIN : UPC : Grocery Disclaimer : Content on this site is for reference purposes only.

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