Many drugs are known to have interactions with foods and beverages. But are patients educated well enough about these interactions, especially about one of the most common ones--the interaction between grapefruit juice and many drugs?
“You can slap incredibly large auxiliary labels or have it typed on the labels, but I don’t think it is good enough.” said Steve Plogsted, PharmD, BCNSP, CNSC, Clinical Pharmacist with the Nutrition Support Service at Nationwide Children’s Hospital, Columbus, OH. “They have all those patient inserts and patient folders, and the information is in there. But is anyone going to take the time to read it all?” he asked.
A warning label on the prescription vial may be enough for some patients, but not for everyone, said Tana N. Kaefer, PharmD, Clinical Coordinator with Bremo Pharmacies in Richmond, VA. Some patients will do fine, but those who have low health literacy will need more explanation and education about food or juice interactions, she said.
Some commercials aimed at consumers now give a warning about an interaction with grapefruit juice, but even that information may not be enough, said Plogsted. Those warnings are “the fast talking at the end of the commercial” to which people have become immune, he said.
Up next: What you can do to educate yourself and your patients
More than 85 drugs are known to have interactions with grapefruit juice, according to the American Pharmacists Association website.1 Grapefruit plays hob with the metabolism of these drugs because it contains furanocoumarins. Furanocoumarins are metabolized by the intestinal cytochrome P450 (CYP)3A4 enzyme into reactive intermediates that then bond covalently to the active site of the enzyme, which irreversibly inactivates it. This inactivation leads to the increased bioavailability of the affected drugs and a potential for toxic effects. Intravenous drugs are usually not affected because grapefruit primarily targets intestinal CYP3A4 and not liver CYP3A4. This interaction is also seen with citrus fruits similar to grapefruit, such as pomelos and tangelos, which are eaten fresh, and Seville oranges, which are primarily used to make marmalade.
Grapefruit products also interact with efflux transporter P-glycoprotein and uptake transporters such as organic anion-transporting polypeptides (OATPs). This reduces absorption, which leads to decreases in blood levels of certain drugs. Apple and orange juice also appear to inhibit OATPs. There have been reports of interactions between warfarin and cranberry juice, as well, possibly due to salicylic acid in cranberries.
The identification of isoenzymes and isoenzyme pathways has led to a larger number of juice/drug interactions being identified, Plogsted said. “Blood levels go up or go down or the drug doesn’t get absorbed.”
The interactions between grapefruit and medications that cause decreased blood levels may be less well known, said Kaefer. Much of the information on these interactions has come out in the last several years or so, she noted.
Plogsted noted that grapefruit juice can be used to enhance absorption for some drugs, such as cyclosporine or tacrolimus. “When we were having bad absorption, we were asking people to take cyclosporine with grapefruit juice rather than escalate their dose and increase the drug costs,” he explained.
“In theory that makes sense, but in practice I don’t know that I would recommend that,” said Kaefer. If a patient suddenly takes a dislike to grapefruit juice or they run out, it can throw everything off, she noted.
But Plogsted admitted that it is probably simpler for a pharmacist to tell a patient not to drink grapefruit juice while taking a medication rather than go into any exceptions to that advice that could confuse the patient.
When it comes to other food and medication interactions, there is also some confusion, Plogsted said. Patients taking anticoagulants may be confused about which vegetables are the leafy green ones—even when given a list of the vegetables to avoid. The message that needs to be heard by these patients is to not change their daily eating habits once blood levels have stabilized, Plogsted said. If they eat broccoli twice a week and everything is stable, they should not change the routine, he explained. Kaefer asks patients about what vegetables they usually eat and explains that they can have some broccoli or Brussels sprouts as long as they are consistent about it. “Don’t suddenly go on an all-salad diet if you don’t ever eat salad,” she said.
Instructions like “take with food” or “take on an empty stomach” may also be open to wrong interpretations, Plogsted added. The gold standard advice for taking a medication on an empty stomach is to avoid taking the drug for one hour before a meal or two hours afterward, he said, but this may not be helpful for people who eat several small meals during the day or don’t eat at the times a medication needs to be taken.
One food and drug interaction now seen less commonly is between MAOIs and foods high in the amino acid tyramine, Kaefer noted. MAOIs are being used less often, but patients taking these drugs should be counseled to avoid cured meats and aged cheeses, among other foods.
Another food and medication issue is potassium intake with ACE inhibitors in elderly patients, both Kaefer and Plogsted said. Patients who may have compromised kidneys must be counseled to avoid high-potassium foods and especially to avoid salt substitutes that contain high levels of potassium. “Grapefruit juice gets all the press and green leafy vegetables with warfarin gets a lot press. But people don’t pay much attention to potassium with the ACE inhibitors.”
1. American Pharmacists Association. Juice interactions: What patients need to know. Available at https://www.pharmacist.com/juice-interactions-what-patients-need-know. Accessed on Jan. 24, 2017.