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Grapefruit Juice-Medication Interactions
Karen Shalansky, Pharm.D.

May 1999 Drug & Therapeutics Newsletter
(C) 1999, CSU-Pharmaceutical Sciences
Vancouver Hospital & Health Sciences Centre

When ingested together, grapefruit juice can interact with various medications, resulting in potentially toxic drug levels and adverse effects.

Certain bioflavonoids contained in citrus juices can affect drug metabolism. The major bioflavonoid in grapefruit juice is naringin, which is partially metabolized by enteral bacteria to form naringenin.1,2 Naringenin is a potent inhibitor of the cytochrome p450 liver enzymes: CYP1A2, CYP3A3 and CYP3A4. There is however, considerable inter-individual variability in the effects of grapefruit juice on drug metabolism, in part due to 1) amount of naringenin formed by an individual, 2) amount of naringin present in a brand of grapefruit juice, 3) dilution of grapefruit juice used, and 4) other substances in grapefruit juice accounting for the interaction.2

Table 4 lists drugs whose levels may significantly increase if given concomitantly with grapefruit juice. CSU Pharmaceutical Sciences will place a label stating "Do not take with grapefruit juice" if a patient is ordered any drug listed below.

Table 4. Grapefruit Juice-Drug Interactions

Drug

Significance

Dihydropyridine Calcium Channel Blockers:
-amlodipine†
-felodipine
-nicardipine
-nifedipine†

AVOID grapefruit juice OR monitor for decreased BP, increased HR if taken together

Terfenadine

AVOID grapefruit juice as may result in cardiotoxicity (prolonged QT interval)

Cyclosporine†

AVOID grapefruit juice, unless prescribed to specifically increase cyclosporine levels

HMG-CoA Reductase Inhibitors (Statins)‡:
-atorvastatin
-cerivastatin
-lovastatin
-simvastatin†

AVOID grapefruit juice as potential for myopathy or rhabdomyolysis¶

Cisapride†

AVOID grapefruit juice as potential for cardiotoxicity (torsades de pointes, prolonged QT interval)¶

Benzodiazepines
-triazolam
-oral midazolam†

AVOID grapefruit juice or monitor for increased sedation if used together

Quinidine†

AVOID; significance unknown

Saquinavir

AVOID; signficance unknown

Estrogens
-ethinyl estradiol†
-17ß estradiol

AVOID - significance unknown

† formulary drugs at VHHSC
‡ fluvastatin and pravastatin are not affected by CYP3A4 inhibitors3
¶ theoretical risk as these adverse reactions have occurred with other CYP3A4 inhibitors4

For further information on this topic on line, refer to: www.powernetdesign.com/grapefruit/

 References

1. McInnes K. Drug interactions with grapefruit juice. CPJ/RPC 1998;131:30-2.

2. Ameer B et al. Drug interactions with grapefruit juice. Clin Pharmacokinet 1997;33:103-21.

3. McEvoy GK (ed). AHFS Drug Information, Bethesda:American Society of Health-System Pharmacists;1999:1555.

4. Sukkari SR. An update on cisapride adverse drug reactions. Can J Hosp Pharm 1999;52:33-4.