How Much Grapefruit Can You Safely Consume On Lipitor (Atorvastatin)?

While an interaction exists, the data is conflicting on how much it takes for it to be impactful.

Question

Is there a safe amount of grapefruit to consume if I'm taking atorvastatin? I'm interested specifically in Spindrift grapefruit sparkling water, which contains 10% grapefruit juice (so 1.2 ounces per can). Thank you.

Asked by nomen nescio On Jun 13, 2019

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jun 17, 2019
Grapefruit Cut Up On Table With Text - How Much Is Safe To Take With Lipitor?

Overview

It has been fairly well documented that grapefruit juice can interact with several drugs, including Lipitor (atorvastatin), a 'statin' medication used to lower cholesterol.

However, how much grapefruit juice one needs to consume to produce a clinically significant drug interaction isn't entirely known.

Several sources report eating as little as one grapefruit can cause issues. In terms of the actual juice, some studies have shown that less than one cup (~240 mL) of 100% grapefruit juice can cause an interaction.

Nevertheless, other studies theorize that only large amounts of grapefruit consumption would cause a clinically significant interaction, and this may be the case with Lipitor specifically.

The FDA-approved prescribing information for Lipitor does warn about a grapefruit juice interaction, but only when consuming very large amounts (1.2 liters of juice!):

Grapefruit Juice: Contains one or more components that inhibit CYP 3A4 and can increase plasma concentrations of atorvastatin [Lipitor], especially with excessive grapefruit juice consumption (>1.2 liters per day).

Overall, it's extremely difficult, if not impossible, to make a definitive determination of how much grapefruit juice you can safely consume if you take Lipitor due to conflicting data.

There is also the very real chance that any one individual may have variability in how the drug they metabolize the drug or whether or not they may be more susceptible to certain side effects...all of which could play a significant factor in the clinical importance of grapefruit interactions.


Why Does Grapefruit Interact?

Grapefruit can interact with drug metabolism via two main mechanisms:

  • Inhibition of the CYP3A metabolizing enzymes
  • Inhibition of organic anion-transporting polypeptides (OATPs)

As it concerns Lipitor, the mechanism behind the interaction is the inhibition of CYP3A enzymes.

Lipitor is metabolized in our body via these enzymes and if their activity is inhibited (by grapefruit consumption), they won't metabolize the drug as efficiently.

This will increase overall drug concentrations in the body, increasing the risk of side effects.

The side effects experienced can certainly vary and may be minor (e.g. headache or GI problems), but the risk of major side effects is there as well.

Perhaps the most concerning potential side effect is rhabdomyolysis, which results in the breakdown of skeletal muscle. Rhabdomyolysis which has strongly been associated with 'statin' drugs, especially in those receiving too high of a dose.

Countless case studies have been published documenting drug interactions with statin drugs that have resulted in rhabdomyolysis. Being aware of potential interactions with 'statin' drugs (and avoiding them) is extremely important for individuals taking these drugs.


How Much Does It Take?

As mentioned, the data is conflicting in terms of how much grapefruit juice you would need to consume to produce an interaction with Lipitor.

Some studies suggest very small amounts will produce an interaction (as little as one grapefruit or one cup of juice).

In fact, one study reported the following:

A daily glass of grapefruit juice increases blood levels of simvastatin and lovastatin by about 260% if taken at the same time (about 90% if taken 12 hours apart), and atorvastatin [Lipitor] by about 80% (whenever taken).

Others state larger amounts are needed to produce a clinically significant interaction. Remember that the prescribing information for Lipitor states that only very large amounts (over 1.2 liters of juice) are of concern.

Unforuntanutely, as you can see, there certainly is conflicting data on the safety of grapefruit juice consumption with 'statin' drugs, like Lipitor.


How Long Does The Interaction Last?

It is important to point out that you cannot avoid the interaction between Lipitor and grapefruit by simply separating their administration time.

This is because grapefruit isn't directly interfering with Lipitor per se, but decreasing its metabolism via CYP3A enzyme inhibition.

Studies report that grapefruit inhibits CYP3A for an extended period of time.

In fact, multiple studies report that it often takes up to three days for enzyme activity to return to normal! The following is reported from two different evaluations on the matter

Recovery [of enzyme activity] is largely complete within 3 days, consistent with enzyme regeneration after mechanism-based inhibition.
Therefore the effect of grapefruit juice decreased time dependently and lasted for at least 3 days after intake. Furthermore, our model gave predicted values in good agreement with the observed values. It is therefore necessary to withhold grapefruit juice for at least 3 days before administration of the drug to prevent grapefruit juice-nisoldipine interaction.

What Are The Recommendations?

It is best to discuss whether or not it is safe to consume grapefruit juice with your doctor.

Like much of the data concerning the interaction, recommendations vary.

One study stated that although there is a known interaction between 'statin' drugs like Lipitor and grapefruit juice, it likely isn't significant for most people. It concluded:

The increased rhabdomyolysis risk from grapefruit juice consumption due to the increased effective statin dose is minimal compared with the greater effect in preventing heart disease. Grapefruit juice should not be contraindicated in people taking statins.

A different study gives a conflicting recommendation, stating that avoiding grapefruit is the only way to entirely prevent a drug interaction from occurring:

Although altered drug response is variable among individuals, the outcome is difficult to predict and avoiding the combination will guarantee toxicity is prevented.

Final Words

The amount of grapefruit juice you stated in your question, around 1.2 ounces, is definitely at the low-end. When studies report interactions, the smallest amount they typically use is around one cup (~240 mL).

Nevertheless, you can't rule out an interaction with Lipitor, even with that small amount.

You should discuss your therapy with your doctor. They may be fine with consuming such a small amount, but will likely monitor you for side effects, just in case.


Summary

Grapefruit and grapefruit juice can inhibit CYP3A metabolizing enzymes, which are responsible for Lipitor (atorvastatin) metabolism. Studies offer conflicting data on just how much grapefruit it takes to produce a clinically significant interaction.

References
  1. Time course of recovery of cytochrome p450 3A function after single doses of grapefruit juice. PubMed
  2. Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. PubMed
  3. Interactions between grapefruit juice and cardiovascular drugs. PubMed
  4. Lipitor Prescribing Information. Access FDA
  5. Grapefruit Juice and Statins. PubMed

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