FRUIT juice may not be a healthy choice when it comes to washing down pills – with grapefruit, orange and apple juices affecting drug absorption, according to new research from Canada.

University of Western Ontario clinical pharmacology professor David Bailey has continued his research into the area of fruit juice and drug interactions.
In the first controlled human study into the drug lowering interaction of juice, researchers found that grapefruit, orange and apple juice all have the ability to decrease the absorption of some drugs. Dr Bailey’s previous research into this area revealed that grapefruit juice was implicated in increasing the absorption of some drugs, via a different mechanism.

Juice and decreased drug absorption

The new research findings were presented at the 236th National Meeting of the American Chemical Society recently. Dr Bailey revealed that along with grapefruit juice, both orange and apple juice are implicated in decreasing the absorption of certain medication such as the anti-cancer agent etoposide.
Certain blood pressure lowering beta-blockers are also affected, such as atenolol, celiprolol and talinolol. Other drugs include the organ transplant rejection drug cyclosporine and some antibiotics including ciprofloxacin, levofloxacin and itraconazole.

During the study, healthy volunteers took the allergy-fighting antihistamine fexofenadine. The subjects took the drug with either grapefruit juice, water containing naringin (a component of grapefruit juice), or plain water.

Results showed that only half the drug was absorbed when taken with grapefruit juice compared to water. The effects of orange and apple juice on decreased drug absorption was drawn from Dr Bailey’s previous research.

It appears that the active ingredient of grapefruit juice, naringin, blocks OATP1A2. This is a key drug uptake transporter that moves the drug from the small intestines into the bloodstream. Therefore, drug absorption is reduced when naringin blocks the transporter.

According to the researchers, orange and apple juice also have naringin-like components that block OATP1A2. In orange juice the culprit is hesperidin but the chemical in apple juice is yet to be identified.

Juice and increased drug absorption

Dr Bailey was the first researcher 20 years ago to indentify the ability of grapefruit juice to increase the absorption of certain drugs. The initial research revealed that the “grapefruit juice effect” had the potential to turn a normal therapeutic dose of certain drugs into a toxic overdose.

Unlike the new findings, a component of grapefruit juice attaches to the intestinal enzyme CYP3A4. This enzyme would normally help to break down drugs such as cholesterol lowering statins and blood pressure lowering calcium channel-blockers.

This means there is more drug in the intestines to be absorbed, leading to a potentially toxic overdose. Subsequently, nearly 50 medications have been identified as being affected by the “grapefruit juice effect”, leading to label warnings on some drugs..

Significance of clinical effect
While the new research reveals the role of fruit juice in drug interactions, Pharmaceutical Society of Australia vice-president and University of Tasmania pharmacy research fellow Dr Shane Jackson cautions that while drug reactions may occur in theory, it is important to know the clinical significance of the effect.

“It is all well and good to find out with this research that there is an effect of juice on drugs, but we must also question if it is clinically significant,” he said.

“Most of the drugs that will have an effect with fruit juice are those drugs [with which] you won’t see a clinically significant effect. For example, you can increase the level of a blood pressure medication by 10 or 20 per cent but it will have limited effect on a person’s blood pressure.

“When you increase other medications, like anti-cancer drugs or digoxin, that have a narrow therapeutic range, then that may have a significant effect.”

Patient education joint responsibility
Educating patients on the risks of mixing certain drugs with fruit juice is important for minimising the potential harm and is a joint responsibility between doctors and other health professionals, according to Dr Jackson.

“Patient education in relation to medication is a joint responsibility between doctor and pharmacist. It is equally the responsibility of both to make sure that when they [the patient] are prescribed a drug, we’re ensuring that it is the appropriate drug for the individual,” he said.

“With drugs like digoxin, fruit juice can have an effect – again it is based on the clinical parameters of the patient. If the drug is not doing what it should be doing, then you need to look at why.

“Pharmacists will often counsel patients against taking grapefruit juice with statin medication and I’m sure GPs do the same. It is an equal responsibility to make sure patients know that there is a possible interaction and it is perhaps more up to the GP to make sure they are monitoring the patient to make sure they’re giving them the desired clinical benefit.”

Low incidence of interaction

When it comes to not mixing drugs and juice, Dr Jackson is confident that the message is getting through to patients.

“Since being a pharmacist, I have seen one or two episodes where grapefruit juice was causing a problem and that problem was to do with statin medication. The levels were getting too high and people were getting muscle pain,” he said.

“Certainly there’s been nothing too extreme and that was because in most cases GPs and pharmacists are warning patients about the possible side effects in relation to taking these medications with grapefruit juice.

“Currently it is not a big issue in practice because of the safeguards in place. There are prompts there to make sure that health professionals are warning their patients about the possible interactions. It is a matter of looking at the drugs with a narrow clinical indication like the cancer drugs and looking at the recommendations of the research that is coming out.”

Need for recommendations

While the researchers recommend patients swallow their medication with water to avoid a potential interaction, Dr Jackson feel more research is needed to clarify the risks between juices and specific medications.

“Once one study raises awareness, another study is needed to confirm the findings,” he said.

“We do know that grapefruit juice interacts with medications. But we need to know the clinical implications and we need that confirmed.

“We need organisations like TGA and the National Prescribing Service to come out with appropriate recommendations about the clinical impact.
“If it is of concern, those organisations will advise the professionals involved and that information will be passed on to patients. Essentially what we need to do is watch this space.”

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