Expert Review: Pharmacotherapy

Food-Drug Interactions

The marketing and consumer use of herbs, food with “anti-oxidant” properties and dietary supplements has risen dramatically in the developed world over the past two decades. Although, the concept of a healthy diet does indeed play a major role in disease prevention, there are some underlying caveats associated with non-disclosed use, interactions with prescription medications or overuse of the same. The problem is more frequently encountered in patients with chronic illness such as cancer or cardiovascular disease.
According to a recent systematic review of the literature, the top five herbs/botanical products, which were documented to have the most interactions with individual medications, were St John’s Wort ( Hypericum perforatum), ginkgo ( Ginkgo biloba), kava ( Piper methysticum), digitalis ( Digitalis purpurea) and willow ( Salix alba). Similarly, the top five mineral/vitamin/amino-acid products were magnesium, calcium, iron, vitamin A and potassium, whereas the top-five dietary supplements were melatonin, coenzyme Q, DHEA (dehydroepiandrosterone) and creatine.
Another recent comprehensive review has highlighted the rising problem of grapefruit juice interaction with concomitant medications. Grapefruit as well as other related citrus-fruits, such as Seville oranges, pummelos, and some exotic orange varieties have been favoured by the public due to their “anti-oxidative” properties. This type of citrus-fruits contains furanocoumarins which irreversibly inhibit cytochrome P450 3A4 isoenzymes in the human body.
These enzymes are responsible for the biotransformation of several drugs leading to either activation of pro-drugs or in-activation of active drugs. In the case of active drugs, inactivation of P450-3A4 leads to lesser inactivation and thus greater amounts of the active drug to enter the systemic circulation. The resulting increase in drug levels can lead to an increase in therapeutic effect, adverse effects and/or toxicity. It has been found that furanocoumarins are capable of decreasing the pre-systemic metabolism of affected drugs taken up to 72 hours after grapefruit consumption. Interactions are most pronounced for drugs that normally undergo a large amount of pre-systemic metabolism (low oral bioavailability). Evidence indicates that following intake of grapefruit, the inactivation of the P450 3A4 isoenzyme is mainly observed in the gastro-intestinal tract and to a lesser extend in the liver. Drugs classes that seem to be affected by grapefruit juice consumption are anti-arrhythmics (amiodarone, dronedarone), anti-histamines (diphenydramine, fexofenadine, astemizole), calcium channel blockers, HMG-CoA reductase inhibitors (statins; lovastatin, simvastatin), sedatives (buspirone) and psychotropics/anti-depressants (carvamazepine, trazodone, fluvoxamine, setraline).
In conclusion, it is recommended that healthcare professionals should pay more attention towards those pairs of interactions and also patients are expected to disclose any information regarding the use of herbs, “anti-oxidant” property foods or dietary supplements.

Citation: H.-H. Tsai, H.-W. Lin, A. Simon Pickard, H.-Y. Tsai, G. B. Mahady. Evaluation of Documented Drug Interactions and Contraindications Associated With Herbs and Dietary Supplements. Int J Clin Pract. 2012;66(11):1056-1078 Bailey DG, Dresser G, Arnold JM. Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? CMAJ. 2012 Nov 26. [Epub ahead of print]

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