Ask the Pharmacist

Q. I noticed there was a “Take with food” label on my naproxen prescription, an “empty stomach” label on my thyroid prescription and on my atorvastatin there is a warning to “avoid grapefruit”. Are these just loose suggestions or are they important to abide by?

A. What you are referring to are known collectively as drug/food interactions. Things are continually changing as more studies and research is done so what was believed 5, 10 even 25 years ago may have changed. Some medications are affected significantly by food since it may enhance or diminish the mechanism of action by which they work and thus the drug’s effectiveness (or lack thereof). In other cases, food may also be suggested to reduce side effects and/or help with respect to convenience and or remembering to take the medications.

For starters, let’s discuss some of the medications that are best taken with food.

For some medications such as the anti-inflammatories (known as the NSAID’s such as ibuprofen & naproxen), corticosteroids (prednisone), opioids (codeine, morphine) and metformin to name a few, the presence of food in the stomach helps to reduce the risk of gastric (stomach) irritation. The amount of food may vary from individual to individual but usually a meal or a full glass of milk is suggested rather than just a couple of crackers in order to protect the stomach.

There are also medications, such as lovastatin (Mevacor) and rivaroxaban (Xarelto), where food is recommended to increase absorption and therefore enhance their effectiveness. Of note, rivaroxaban is dose dependent when it comes to food. In other words, at a low dose of 10mg, it can be taken with or without food whereas at the 15 and 20mg doses results are better if it is taken with food.

Next, there are instances where taking your medication on an empty stomach is prudent to improve absorption.

In most scenarios, one hour before or two hours after signifies an empty stomach. The medications that fall into this category are iron (ferrous gluconate, ferrous sulfate, ferrous fumarate), levothyroxine (Eltroxin, Synthroid), some antibiotics (norfloxacin, tetracycline) and bisphosphonates (alendronate, and risedronate with the exception of Actonel DR which is recommended to be with food) and more.

Iron specifically requires a mildly acidic environment for the best absorption. To accomplish this, taking iron with ascorbic acid helps to provide the proper stomach environment to maximize effects. It is best to use a 500 – 1000mg vitamin C tablet which allows for a 10% increase in absorption as opposed to taking the iron with orange juice. One cup (250ml) of OJ only provides 124mg of vitamin C so that would mean one would have to consume many cups of juice to provide the same effect as a single Vitamin C tablet. As tasty as orange juice may be, it certainly isn’t good for your body to drink that volume of juice (which is chock full of sugar).

For those people that take both iron and levothyroxine, due to an interaction that occurs between them, not only is it important to take them both on an empty stomach but they also need to be separated by at least 4 hours from each other to maximize your results. This becomes increasingly difficult when calcium supplements are introduced to the mix as calcium needs to be at least 4 hours away from both iron and thyroid medications.

There are also instances when an empty stomach can help with increasing a drug’s effect such as is the case with proton pump inhibitors (pantoprazole, omeprazole). It is best to take this class of drugs 30 to 60 minutes before a meal to ensure you get the maximum benefit from them. One exception to this rule is dexlansoprazole (Dexilant); it has a dual-release mechanism which enables it to be taken without regard to meals.

Lastly, there is the well-documented and well-known interaction between grapefruit and medications. There are several mechanisms that are responsible for this interaction and the clinical significance depends on the mechanism.

People often inquire if they are allowed to eat or drink grapefruit in the morning if they take their affected medication later in the day. Well, that all depends on which mechanism the interaction is affected by. The most serious of grapefruit interactions is due to the inhibition of the CYP3 enzymes which affects the metabolism of a specific number of medications that also are eliminated from the body by this same pathway. For this interaction, full recovery from the enzyme interaction can take up to 72 hours (i.e. 3 days). So the answer to the question in this case would be to avoid grapefruit and its juice altogether.

A list of a few of the medications affected by this type of interaction are amiodarone (Cordarone), some calcium channel blockers (nifedipine, felodipine, and verapamil), some cholesterol medications (atorvastatin, lovastatin, simvastatin) and ticagrelor (Brilanta). Due to the fact that our body does change as we mature, there are some medications that grapefruit needs to be avoided due to this interaction, but in these cases, only in the elderly.

Some examples of medications that fall into this category are apixaban (Eliquis), domperidone, oxycodone and quetiapine (Seroquel). Interestingly, there is another mechanism of action that does allow for some affected medications to be dosed 4 hours later so that grapefruit and its juice need not be totally avoided. If taking levothyroxine, acebutolol (Sectral), fexofenadine (Allegra) or Rasilez, be sure to separate them from your grapefruit intake by at least the recommended 4 hours.

Lastly, some grapefruit interactions are volume dependent and therefore drinking/ consuming grapefruit is fine as long as less than 3 glasses of grapefruit juice in a single day are drank. This applies to only a few drugs like warfarin and methylprednisolone.