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Grapefruit Juice and Drug Interactions

Huyen-Vi Khong, Pharm. D. Candidate

This is a research paper written while on a clinical rotation in an anticoagulation clinic as student at the University of Colorado School of Pharmacy.

Please note that most of these interactions do not involve warfarin.  However, this paper was well researched and many of the readers of warfarinfo.com also take these other medications, so I thought it was important enough to include it on this website.

 Grapefruit juice has been found to interact with many different medicines that are often used by senior patients.  Grapefruit juice contains a substance (not well determined) that seems to be responsible for the drug interactions.  Orange juice, on the other hand, shows no such drug interactions when it is taken with medicines.  Therefore, orange juice is highly recommended for the same basic nutrients.  Approximately 1 glass of grapefruit juice 3 times daily for 2-3 days is enough to produce significant drug toxicity.  However, eating one grapefruit daily probably does not furnish enough of the interacting ingredient to cause a major problem. Grapefruit juice and its drug interactions can cause serious potential health problems with these medications:


Calcium Channel Blockers (CCB) for high blood pressure and heart rhythm:
· Felodipine (Plendil)
· Nifedipine (Adalat, Procardia)
· Nimodipine (Nimotop)
· Nisoldipine (Sular)
· Nitrendipine (Baypress)
· Verapamil (Calan)

Grapefruit juice with these can cause dangerously low blood pressure, very slow heart rate, irregular heart rate, fluid retention, chest pain (unstable angina), heart attack, or death.

Lipid -Lowering agents for high cholesterol:
· Astorvastatin (Lipitor)
· Lovastatin (Mevacor)
· Pravastatin (Pravachol)
· Simvastatin (Zocor)

Grapefruit juice with these can cause a severe muscle breakdown called rhabdomyolysis.  This can be a fatal condition.

Benzodiazepines for sleep or anxiety:
· Diazepam (Valium)
· Triazolam (Halcion)
· Midazolam (Versed)

Grapefruit juice with these can cause confusion, shortness of breath, slurred speech,  poor coordination, or coma.

Immunosuppresant agents for organ transplants:
· Cyclosporin (Neoral)
· Sirolimus (Rapamune)
· Tacrolimus (Prograf)

Grapefruit juice with these can cause organ rejection, kidney problems, liver problems and loss of sensation (usually in fingers or toes).

Antipsychotic agent:
· Pimozide (Orap)

Grapefruit juice with this can cause dizziness, sedation, irregular heart beat and sudden death.

Antianxiety agent:
· Buspirone (Buspar)

Grapefruit juice with this can cause dizziness, sedation, irregular heart beat and sudden death.

Anticonvulsant agent:
· Carbamazepine (Tegretol)

Grapefruit juice with this can cause dizziness, drowsiness, nausea, vomiting, tremor, agitation, seizures and coma.

Antifungal agent:
· Itraconazole (Sporanox)

Grapefruit juice with this can cause a treatment failure which could lead to death if an internal fungal infection is the problem being treated.

Anticoagulant agent:
· Warfarin (Coumadin)

There have been conflicting reports about the effect of grapefruit juice on warfarin.

Mr. Lodwick did see the following patient.  A middle-aged man with liver disease was taking warfarin and atorvastatin (Lipitor).  He consumed approximately two gallons of pink grapefruit juice over three days.  He developed severe muscle pain and cramps to the point that he was unable to eat.  His INR increased into the 6 to 7 range and he developed bloody diarrhea.  About three days after he finished the grapefruit juice, he was given a dose of vitamin K by mouth.  The next day the bloody diarrhea stopped and he began to return to normal.

References:  Lodwick, A. Warfarin Interactions: The Consequences of Upsetting the Balance Between Warfarin and Vitamin K.  Colorado Society of Health-System Pharmacists. Poster Presentation. Aurora  CO  October 1999.

Maudlin, R. Grapefruit Juice - Physiological Effect; Drug Interactions. Modern Medicine 1999;67:59

Micromedex Database. 

© 2000 Huyen-Vi Khong Used by Permission

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Last updated January 1, 2006