Some things just aren't meant to go together.  Doctors have long known that a combination of two or more prescription drugs can sometimes be lethal. A study just published in the Canadian Medical Association Journal warns that a certain kind of fruit - or the juice of that fruit - can sometimes be deadly if combined with the wrong prescription drug.

We're talking about the interaction between grapefruit in combination with one of a growing list of more than eighty-five drugs, most of which are available in Canada.  And we're talking about all forms of grapefruit: whole fruit, freshly squeezed grapefruit juice and frozen concentrate.

One whole grapefruit or two hundred ml of grapefruit is enough - when combined with one or more of the list of dangerous drugs - can cause side effects that range from annoying to serious and even lethal.  Seville oranges (the bitter variety often found in marmalade), limes and pomelos also cause this interaction. Fortunately, if you love citrus fruit, sweet oranges such as navel or Valencia are safe.

A large and growing list of prescription drugs are metabolized or broken down in the liver by an enzyme called CYP450 3A4. Grapefruit contains chemicals called furanocoumarins.  These bind to CYP3A4 and inactivate it irreversibly - meaning any drug that is ordinarily broken down by the enzyme does not get broken down and thus rises in the blood stream to toxic and even life threatening levels. There are eighty-five drugs on the list - forty three of which can cause serious side effects - up from just seventeen four years ago.

As more pharmaceutical drugs come onto the market with this effect, more and more patients are at risk.

The most serious is a heart rhythm disturbance called torsade de pointes.  It can occur when patients on certain heart drugs have grapefruit and can also occur in patients who do not have a heart condition but are taking some forms of cancer chemotherapy.  Some cholesterol-lowering drugs taken with grapefruit can cause severe damage to muscles and a condition called rhabdomyolysis - a condition that a cause the kidneys to fail.  Other drugs in combination with grapefruit can cause kidney failure. 

Other serious side effects include dizziness, over-sedation and low blood pressure.  Although the connection is considered uncertain and controversial, some studies have suggested that post-menopausal women on hormone replacement therapy might have an increased risk of breast cancer.  However, other studies have failed to demonstrate this link.

Some of the most serious cases of adverse effects have been reported for heart rhythm drugs like amiodarone and a drug for heart rhythm and blood pressure called verapamil. The cholesterol lowering drugs atorvastatin and simvastatin have reportedly caused the muscle damage condition I talked about called rhabdomyolysis. However, the drug rosuvastatin (known commercially as Crestor) is not metabolized by CYP3A4 and is therefore safe to take with grapefruit.

 A form of estrogen hormone replacement when taken with grapefruit has reportedly triggered a blood clot in the leg.  Certain sleeping pills can also trigger the heart rhythm disturbance I was talking about.

The authors of the CMAJ study say all patients age forty-five and up need to pay attention to the risk, since people in that age group are the main consumers of grapefruit and receive the most prescriptions for drugs.  Patients age seventy and up are more likely to have more extreme forms of the drug-grapefruit interaction.  Elderly patients are also less likely to have the capacity to compensate for elevated drug levels caused by eating grapefruit. 

Some doctors are not aware that the list of medications that react badly to grapefruit is growing.  Many patients do not volunteer that they like grapefruit and doctors may not ask.  So, if you like grapefruit and you want to be safe, tell your doctor every time you get a new prescription.  And if you want to be safe without having to think too much about it, you may want to consider choosing a new favorite fruit.