Grapefruit Mixed With Prescription Drugs Have Severe Side Effects

Many prescription drugs have severe side effects when they are mixed with grapefruit, and the number of these medications is rapidly growing, however, doctors are often unaware of the side effects, according to a new study published in the Canadian Medical Association Journal (CMAJ).

28 Nov 2012 --- Paradoxically, in another study published earlier this year, researchers said that grapefruit juice can actually help anti-cancer drugs work better.

The new study is an analysis by the same experts who found these interactions over 20 years ago and provides evidence that may help doctors understand the consequential side effects that can come with consumption of grapefruit mixed with some prescription medications.

Dr. David Bailey, from the Lawson Health Research Institute in London, Ontario, and his team, commented:

  "Many of the drugs that interact with grapefruit are highly prescribed and are essential for the treatment of important or common medical conditions. Recently, however, a disturbing trend has been seen. Between 2008 and 2012, the number of medications with the potential to interact with grapefruit and cause serious adverse effects has increased from 17 to 43, representing an average rate of increase exceeding 6 drugs per year. This increase is a result of the introduction of new chemical entities and formulations."



Serious side effects of mixing grapefruit with certain prescription drugs include:
- respiratory failure
- gastrointestinal bleeding
- bone marrow suppression in patients with weak immune systems
- renal toxicity
- acute kidney failure
- sudden death

The researchers explained:

  "Unless health care professionals are aware of the possibility that the adverse event they are seeing might have an origin in the recent addition of grapefruit to the patient's diet. It is very unlikely that they will investigate it. In addition, the patient may not volunteer this information. Thus, we contend that there remains a lack of knowledge about this interaction in the general healthcare community."



According to the new findings, over 85 different medications may have interactions with grapefruit, and 43 can have harmful effects. Seville oranges, which is found in marmalade, as well as limes and pomelos have the active ingredients, or furanocoumarins - substances which naturally occur in grapefruit. They irreversibly inhibit the drug metabolizing CYP3A4 enzyme that inactivates the effects of approximately half of all medications.

Medications that mix with these substances have three traits:
- They are given as oral drugs.
- They possess very low to middle bioavailability (the percentage of the oral dose of the medication which is soaked into the blood circulation unaltered).
- They go through drug metabolism in the gastrointestinal tract by CYP3A4.

For low bioavailability drugs, consuming just one grapefruit can multiply the dosage effect of that medication several times, and this interaction can take place regardless of whether the grapefruit was eaten hours before the drug was taken. Therefore, a moderate amount of grapefruit can impact interacting medications which are taken only once a day at any hour during when the dose is taken.

Taking regular amounts of medications on a daily basis can increase side effects. For example, when Simvastin, a popular statin, is mixed with one 200-mL glass of grapefruit juice for 3 days, it results in a 330% systematic concentration of the medication in comparison with water.

Adults over the age of 45 are the most common buyers of grapefruit and also tend to be prescribed the most medications. The population of adults over 45 is extremely large, therefore, many of these interactions are likely to occur. The report notes that older adults are more likely to have decreased capability to endure extreme systematic drug concentrations, making them more likely to experience these adverse effects.

The authors concluded:

  "The current trend of increasing numbers of newly marketed grapefruit-affected drugs possessing substantial adverse clinical effects necessitates an understanding of this interaction and the application of this knowledge for the safe and effective use of drugs in general practice."