PEN® eNews 15(4) April 2025 - Food-Drug Interactions

Do Non-Warfarin Anticoagulant Medications Still Interact With Grapefruit?

Which foods/ dietary supplements interact with warfarin or other anticoagulant medications?

Although non-vitamin K antagonist oral anticoagulants (NOACs) offer an alternative to warfarin therapy, their interactions with food and dietary supplements have rarely been examined in human in vivo studies. Given the theoretical potential of foods and supplements that strongly potentiate or inhibit P-glycoprotein or CYP3A4 metabolism to adversely interact with NOACs, individuals taking NOACs would be prudent to avoid foods and supplements that strongly potentiate or inhibit these mechanisms and to only consume foods and supplements with moderate or minor theoretical effects under close supervision.

Examples of NOACs include dabigatran, rivaroxaban, apixaban and edoxaban.

To see the full practice question, including the Evidence Statements, Remarks and References, click here.

Which Fruits and Juices Commonly Interact With Medications?

Are there any fruit or fruit juices that should be avoided when taking medications?

Drugs that can be expected to interact with grapefruit and grapefruit juice are drugs that:  

• are taken orally,

• have incomplete (i.e. very low to intermediate) bioavailability and

• are largely metabolized by CYP3A4.  

The magnitude of this response will vary widely across the population and may or may not be clinically important. Seville orange and pomelo juice also affect CYP3A4 metabolism, although these fruits were not seen to have as many interactions or as large effects as grapefruit juice did. 

If all three of the above criteria are met, it would be prudent for individuals to avoid grapefruit and grapefruit juice or to switch to an alternate drug (if possible/ preferred). If one or two of the above criteria are met, it would be prudent to allow grapefruit and grapefruit juice consumption as long as side-effects are monitored closely. 

Although non-grapefruit fruits and juices can interact with some medications, none have been found to have deadly impacts the way that grapefruit can. 

To see the full practice question, including the Evidence Statements, Remarks and References, click here.

Does a Ketogenic Diet Affect Medication Efficacy?

How does following a ketogenic diet affect the efficacy and safety of certain medications (e.g. anti-epileptic, anti-diabetic, cardiovascular)?

It is possible that a ketogenic diet may interfere with the efficacy and increase the adverse effects of some medications. Although some effects may be positive (e.g. may augment the antipsychotic effects of some psychiatric medications), individuals who take medications chronically should not follow a ketogenic diet without first discussing the possible interactions with a specialist.

It should be noted that KD side-effects (e.g. constipation, dehydration, fatigue, acidosis) can lead to discontinuation of the diet, especially in children and individuals with autism spectrum disorder or bipolar disorder. 

See Additional Content: Nervous System-Pediatric Epilepsy: Ketogenic Diet Knowledge Pathway 

To see the full practice question, including the Evidence Statements, Remarks and References, click here.

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