While you would expect that interactions could take place between drugs and indeed between herbal medicines and drugs, drug interactions with fruit do not immediately jump to mind. And while I was aware that grapefruit juice did not mix well with a couple of medicines, I had no idea how many drugs actually can interact with the humble grapefruit.
According to an article in the latest issue of the Canadian Medical Association Journal written by the researchers who discovered a potential link some 20 years ago, there are more than 85 drugs that may interact with the fruit, 45 of which can have serious side-effects. These include sudden death, acute kidney failure, respiratory failure, gastrointestinal bleeding, and bone marrow suppression in immunocompromised people.
“Many of the drugs that interact with grapefruit are highly prescribed and are essential for the treatment of important or common medical conditions,” writes Dr David Bailey of the Lawson Health Research Institute in London, Ontario. “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. This increase is a result of the introduction of new chemical entities and formulations.”
It turns out an interaction can occur even if grapefruit is consumed many hours before taking the medication. Frequent daily consumption of a regular amount can further worsen the effect. For example, simvastatin, a commonly used lipid-lowering statin, combined with a 200ml glass of grapefruit juice once a day for three days, produces a 330 per cent rise in the systemic concentration of the drug compared with someone who drinks water.
And it seems that other fruits such as Seville oranges and limes also contain the furanocoumarins that lie at the heart of the problem. These chemicals are innate to the fruit and cause the interaction by irreversible inhibition of the CYP3A4 liver enzyme that normally inactivates the effects of an estimated 50 per cent of all medication. So with the decreased amount of this enzyme, drug levels in the blood can shoot up dramatically.
The medications that interact with furanocoumarins have three characteristics: they are taken orally; they have what’s known as low bioavailability (the percentage of the oral dose of a drug absorbed into the blood circulation unchanged) and they undergo drug metabolism in the gastrointestinal tract by CYP3A4. Benzodiazepines, used as sleeping tablets and anxiolytics, and certain antihistamines are affected. For drugs with very low bioavailability, ingestion of a single normal amount of grapefruit can be analogous to consuming multiple doses of the drug alone.
Grapefruit juice and Viagra can make you breathless, it seems. Or at least cause flushing, headaches and upset your tummy. Cardiac drugs such as nifedipine and amlodipine, mixed with grapefruit juice, can cause low blood pressure and a high heart rate.
The authors of the review say there is a lack of knowledge among doctors about the extent of the drug/grapefruit interaction. “Unless healthcare 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.”
Never a particular fan of the sour-tasting grapefruit, I recall its starring role in “posh” hotel dinners of the 1970s. It looks like its popularity may fall, certainly among those obliged to take multiple medications on a daily basis.