American Society of Endocrine Physician Assistants

 

 

GRAPEFRUIT JUICE AND DRUGS

HOW DOES GRAPEFRUIT JUICE AFFECT THE DRUGS I AM TAKING?

Grapefruit juice blocks cytochrome P-450 3A4 and Ia2 (CYP3A4 and CYP1A2) enzymes in your intestinal wall. Common to all living organisms, the body has evolved the cytochrome P-450 system, a superfamily of enzymes responsible for removing drugs and toxins from the body. The cytochrome P-450 3A4 subfamily, located predominantly in the liver and intestinal tract, is one of the most common enzyme systems for metabolizing drugs. Most drugs are lipid-soluble or"fat-loving", so that they are readily absorbed in your bloodstream. To eliminate these drugs, however, in the cytochrome P450 system either breaks them down in the gut or changes them in to a more water-soluble or "water-loving" version in the liver. The kidney can then eliminate them in the urine. Thus, the liver,gut, and kidney work together to prevent excessive amounts of drug and/or toxins from getting in to your bloodstream. Grapefruit juice blocks the cytochrome P450 3A4 enzyme systems in your gut. By inhibiting this defence mechanism, grapefruit juice may increase the blood levels of some drugs. Therefore, you may experience adverse effects from the drugs you are taking when taken with grapefruit juice.

WHICH SUBSTANCE IN THE GRAPEFRUIT JUICE IS RESPONSIBLE FOR THESE INTERACTIONS WITH DRUGS?

The precise chemical nature of the substance in the grapefruit juice that inhibits gut wall CTP 3A4 enzymes is unknown. It has been suggested that flavanoids, coumarin, or psoralen derivatives in the grapefruit juice could be the inhibitors. The amount of inhibiting substance in grapefruit juice may vary by brand, concentrations and storage conditions.

I DRINK ONE GLASS OF REGULAR GRAPEFRUIT JUICE WITH BREAKFAST IN THE MORNING, WILL THIS AFFECT THE DRUGS I AM TAKING?

Yes. Regular grapefruit juice is prepared by diluting frozen grapefruit juice with normal amount of water. Double-strength grapefruit juice is prepared by diluting frozen grapefruit juice with half the normal amount of water. One glass of regular grapefruit juice is enough to significantly raise the blood levels of the number of drugs.

FOR HOW LONG DOES THE GRAPEFRUIT JUICE INHIBIT CYP 3A4?

The inhibitory effect of grapefruit juice on CYP 3A4 can last for several hours. A recent study found increased blood levels of calcium-channel blocker felodipine (Plendil) even when the drug was given 24 hours after drinking grapefruit juice.

I TAKE AN EXTENDED RELEASE PRODUCT, IS THIS ALSO AFFECTED BY GRAPEFRUIT JUICE?

Yes. Grapefruit juice increases the blood levels of extended release preparations. Recent studies have shown increased blood levels of extended release felodipine,extended release nifedipine (Adalat, Procardia) when taken with grapefruit juice.

WHICH DRUGS ARE AFFECTED BY GRAPEFRUIT JUICE AND WHAT HAPPENS WHEN THEIR BLOOD LEVELS INCREASE?

CYP 3A4 is involved in the metabolism of many medications. When CYP 3A4 is inhibited by grapefruit juice, the blood levels of many medications may rise. Examples of drugs reported to interact are listed in the table below. Since many more drugs are likely to interact, it is important to ask your doctor or pharmacist if you drink grapefruit juice and are taking any medications.

DRUGS AFFECTED BY GRAPEFRUIT JUICE DRUGS AFFECTED BY GRAPEFRUIT JUICE
   
Calcium channel blockers

a) Felodipine (Plendil)

b) Nifedipine (Procardia XL, and Adalat CC)

c) Nimodipine (Nimotop)

d) Verapamil (Calan, Isoptin)

Flushing headache, increased heart rate
decreased blood pressure




Decreased heart rate, constipation,
decreased blood pressure

2. Nonsedating antihistamines

a) Terfenadine (Seldane) [currently off the market]

b) Astemizole (Hismanol)

EKG abnormalities (prolongation of QT
interval) and ventricular arrhythmias
3. Benzodiazepines

a) Alprazolam (Xanax)

b) Triazolam (Halcion)

c) Midazolam

Increased sedation






4. Cholesterol lowering drugs

Lovastatin (Mevocor)

[expect others such as Simvastatin (Zocor)
and atorvastatin (Lipitor)

Caffeine

Immunosuppressive agents

a) Cyclosporine (Sand immune and Neoral)

b) Tacrolimus (Prograf)

Headache, gastrointestinal complaints, and muscle pain.



Nervousness, over stimulation

Kidney toxicity and increased susceptibility to infections


 

WHAT DO YOU RECOMMEND?

Avoid grapefruit juice if you are taking any of the above medications. Since many other drugs may also be affected by grapefruit juice, consult your doctor or pharmacist regarding possible interactions between your medications and grapefruit juice.