Published: 5 March 2015

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Fruit Interactions with Common Medicines

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Prescriber Update 36(1): 4-5
March 2015

Medicine interactions with grapefruit juice are well-known. Research shows that other fruit juices as well as whole fruit, fruit pulp and fruit extracts have also been associated with altered drug metabolism and subsequent interactions. Variability in fruit strains, environmental conditions, processing procedures, and patient factors make it difficult to predict whether a fruit or fruit product will lead to a medicine interaction. ¹

Why do these interactions occur?

Some fruits contain flavanoids and furanocoumarins which can interfere with medicine metabolism.
The cytochrome p450 isoenzyme, CYP3A4, is inhibited by the flavonoid, naringin, as well the furanocoumarins bergamottin and 6',7'-dihydroxybergamottin.¹ When CYP3A4 is inhibited, it can result in increased concentrations of medicines that are metabolised by this enzyme. Another cytochrome p450 isoenzyme, CYP2C9, may be inhibited by pomegranate and cranberry juices.¹

Furanocoumarins can inhibit P-glycoproteins that are also involved in medicine metabolism (www.medsafe.govt.nz/profs/PUArticles/P-glycoproteinSept2011.htm).

Organic anion-transporting polypeptides (OATPs) are membrane transport proteins which facilitate substance uptake. ¹ These proteins can be inhibited by orange, apple, and grapefruit juices. ¹

Which fruit and fruit products can cause these interactions?

Fruits associated with medicine interactions include orange, pomelo, pomegranate, cranberry, grape, apple, and grapefruit. These whole fruit and their products including fruit juices, fruit concentrates, fruit pulp, fruit jams/marmalades, fruit extracts and even cooked products such as sauces (for example apple and cranberry sauce) may have an impact on the clinical effect of affected medicines. It is important to note that apple and orange juices or concentrates are frequently used as bases for fruit drinks, often advertised as other flavours. The effect of alcohol made from fruit has not been investigated.

Which medicines are affected by these interactions and how should patients be advised?

The table below lists some of the better established interactions with medicines, it is not a complete list.

Table 1. Possible fruit, juice and supplement interactions with commonly prescribed drugs^{2, 3}

Fruit/Juice/Supplement	Drug	Recommended Actions
Cranberry	Warfarin	Avoid drinking cranberry juice or taking cranberry capsules/concentrates where possible
Grapefruit	Amiodarone	Avoid grapefruit juice
	Atorvastatin	Avoid large quantities (more than 1.2 litres daily) of grapefruit juice
	Carbamazepine	Avoid grapefruit juice and the whole fruit
	Felodipine	Avoid grapefruit juice and the whole fruit
	Simvastatin	Avoid grapefruit juice and the whole fruit
	Tacrolimus	Avoid grapefruit juice and the whole fruit

Adapted from New Zealand Formulary - Interactions

Further information about fruit/medicine interactions is available in Stockley's Drug Interactions.

Please report any suspected adverse medicine reactions and interactions to the Centre for Adverse Reactions Monitoring (CARM).

References

1. Jones S., Preston C.L., Sandhu H. 2014. How fruit juice interacts with common medicines. Pharmaceutical Journal 293 (7831): 369-372.
2. Stockley IH. 2002. Stockley's Drug Interactions. London: Pharmaceutical Press.
3. NZF - Interactions Stockleys. http://nzf.org.nz/nzf_9751