The Truth about Grapefruit and Drugs


Ever wonder why a prescribed medicine has "avoid taking with Grapefruit" written on the bottle?

Well I did, and the prescribing information never says what the interaction is, or how it affects the drug. The reason, it turns out is that furanocoumarins (FC) in our grapefruit can INCREASE the activity of the medication by inhibiting an enzyme that metabolises certain drugs - which could be bad if it increases side-effects, or good if it improves effectiveness or reduces the dose needed and therefore the cost. FCs can occassionally lower some medication, such as fexofenadine (eg the antihistamine Fixofast).

The effect may be minimal with a glass of Grapefruit juice (250ml), while over a litre can produce significant results (apart from making your urine too acid).

Merck & Co who produce Lipex (simvastatin, an HMG-CoA reductase inhibitor that lowers cholesterol levels) state:

"Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma levels of medicines metabolised by CYP3A4. The effect of typical consumption (one 250ml glass daily) is minimal (13% increase in active plasma HMG-CoA reductase inhibitory activity as measured by the area under the concentration-time curve) and of no clinical relevance. However, very large quantities (over 1 litre daily) significantly increase the plasmas levels of HMGCoA reductase inhibitory activity during simvastatin therapy and should be avoided."

One might well ask but WHY? The slighly higher levels of simvastatin are unlikely to be toxic, given some people need up to 80mg/day, so if you are on 40mg/day and drink some grapefruit juice, you might just get a marginally better response!

Interactions that are significant

A list of interactions and a comment on them is available on-line at the Australian Prescriber in an article by Janet McNeece, Senior Pharmacist, Medicines Information Centre, Royal Adelaide Hospital, Adelaide (February 2002).

The important ones are listed below with a comment about their significance:

  • Amiodarone: Increased serum concentration - potentially harmful.
  • Amlodipine: Increased serum concentration - not thought significant.
  • Atorvastatin: Increased serum concentration by 20-50%, could be used to achieve a good response at a lower dose.
  • Carbamazepine: Increased serum concentration by 40%, could be used to achieve a good response at a lower dose, potential toxicity.
  • Cisapride: Some increased serum concentration, unkown significance.
  • Cyclosporin: Significantly increased serum concentration, could be used to lower dose & cost. potential toxicity
  • Diazepam: Increased serum concentration by 1.5x - not thought significant.
  • Felodipine: Increased serum concentration by 2-3x - potentially harmful.
  • Itraconazole: Decreased oral bioavailability - potentially less effective.
  • Nifedipine: Increased serum concentration by 33%, but little clinical effect.
  • Simvastatin: Increased serum concentration - of unknown significance.
  • Tacrolimus: Increased serum concentration - potentially harmful.
  • Warfarin: No change in serum concentration or effect!
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