Why does grapefruit interfere with certain medications?

I’m on a medication that basically makes grapefruits toxic to me-- eating one could cause the level of the medication in my system to spike to about 600%, enough to kill me. (I really wonder why the doctor never mentioned that particular side effect. I like grapefruit! I used to drink Ruby Red in college before I was on this medication!)

What causes grapefruit to harmfully interact with medications, in layman’s terms?

Many drugs are broken down (metabolized) with the help of a vital enzyme called CYP3A4 in the small intestine. Grapefruit juice can block the action of intestinal CYP3A4, so instead of being metabolized, more of the drug enters the blood and stays in the body longer. The result: too much drug in your body.


I never heard of this until you posted it. Weird! search “grapefruit interaction” and there are some articles.
I was just about to post that same fda.gov article.

Because of this statement in the article: “the juice lets more of the drug enter the blood” I’m wondering if grapefruit can help ppl save money on prescription drugs: Take a fraction of the dose and a slice of grapefruit every day and voila! Poor people can now afford statins, anti-anxiety meds, and others previously out of their price range. This should be studied!

The exact amount that ends up absorbed will vary wildly based on how much grapefruit juice consumed, how much o the enzyme blocker it contains, the amount of intestinal surface area of the person in question, what other foods they took with the med and grapefruit at the same time, etc. Drug-food interactions are not easily quantified. Easier to say "in the average person who avoids grapefruit, this amount of drug works this effectively. Avoid Grapefruit while on this med.

Hopefully you aren’t on any of the medications affected - I would expect that your physician would have told you about the interactions, and they are also going to be on the label of the pill bottles.

Grapefruit interacts with so many different commonly prescribed medications, that are used for so many different things, and in so many ways, that it really should be a cultural expectation that if you’re taking any pill at all you avoid grapefruit until and unless you’ve discussed it with a doctor or pharmacist. Think of how recent some of the (hopefully) common knowledge about widely used drugs is - “don’t give aspirin to infants” and “be very careful about dosing Tylenol or mixing it with alcohol” were not well-known by people outside the medical profession until the late 70s. This really needs to be part of that general health education.

To add, many medications come in an extended release version, designed to metre out delivery over a long period. Grapefruit can wreck this. That isn’t going to be a happy thing.

My oncologist allows me half a grapefruit now and then, but it does utilize the same pathway as Tamoxifen. So does Benadryl, which I’ve simply been told not to use.

So do I. I’d heard about this in connection with statins, and when the time came for my doctor to prescribe one for me, he made a point of saying I couldn’t have grapefruit any more.

I hadn’t heard of the same effect with other drugs, but surely it’s s basic professional duty for a doctor to be proactive in warning someone about a potential serious side-effect, even when it might be common knowledge, and is indicated in the patient information leaflet.

I am humbled. I had no idea that grapefruit interaction was a thing.

Ignorance (mine) fought.

Too bad it’s not that simple!

Am I remembering this right? Those taking statins can’t have Earl Grey tea, either. One of the flavorings in Earl Grey is bergamot, a citrus related to grapefruit. It has been a long while since I was first prescribed statin drugs, though, so this might be off.

Why only grapefruit, among all other delicious citrus? Oranges, lemons, limes, etc. do not carry this warning. What is it about grapefruit?

I know, right? Why can’t it be broccoli? It’s already poisonous and tries to warn you with it’s horrible taste!*

I got put on some cholesterol meds and the doctor explained to me pretty much what’s been posted on this thread. All I could hear is “what a drag it is getting old”

*With apologies to The Simpsons and the Stones.

As Bette Davis said, old age is not for sissies. Once you’re on longstanding medications, it’s a constant process of checking for clashing side-effects (I’m right in the middle of such at the moment - I feel fine, but my GP practice get in a tizz if anything is even slightly variable outside the normal range: sometimes I think it ought to be me saying “Well, when you get to my age”, but I should be grateful they are taking care of such things with all the Covid pressures going on).

LOL, I have the opposite problem with my patients. They go nuts over having any lab value that’s not ‘euboxic’ (within the declared normal range) and I have to tell them it’s perfectly normal for their age/condition.

I’d say I wish I had you for my patient, but I wouldn’t wish that one anyone here. (Well, maybe a few people here)

Heh. (For new Dopers: Qadgop treats patients who are prisoners.)

I must find a way to work that word into conversation. Frequently.

The peels of other citrus are also a potential issue. Not so much the juice. I have never been warned about Earl Grey, though I switched away from lemon and orange peel-based cleansing products as well as grapefruit.

Arrgh. This post has brought me out of SD retirement. My second career, no, third career was in a clinical chemistry research lab, which started and spun off a commercial pharmacogenetic (AKA PGX in the biz) testing lab. CYP3A4 is an enzyme that metabolizes certain drugs, and several compounds in grapefruit juice attach themselves permanently to the enzyme, jamming it up. Enough jammed enzymes reduces metabolic capacity, and the active parent drug is not metabolized as quickly as it would be otherwise. So, someone can overdose on a normal dose of medication when eating or drinking grapefruit.

But that’s just half of the story. There are other drug metabolizing enzymes: CYP1A2, 2D6, 2C9, and 2C19. They can be interfered with by other drugs or compounds, creating other unwanted reactions and potential overdoses. Point mutations in the genes that code for the enzymes can also occur that reduce the speed at which an enzyme can metabolize a drug. Back in the day, we were all over creating a dosing algorithm for Warfarin based on these point mutations in CYP2D6 (I think) and VKORC1. Today, as I understand it, PGX testing is most effective for dosing psychiatric and some chemotherapeutic drugs.

I have a mutation in CYP2C19 that makes me a slower metabolizer of some drugs, like Prilosec. I used that to my advantage years ago when I had intractable heartburn from a hernia. I could take 1 OTC Prilosec every 36 hours instead of the usual 18-24 hours.

Going even further (indulge me here), some Asian populations have a slow ADH1 enzyme that is part of the alcohol metabolic process. They have a lower tolerance for alcohol and more adverse effects. Native North Americans descended from Asians with this slow ADH1 have long struggled with alcoholic products introduced by people with European ancestry who have a normally functioning ADH1 enzyme.

My doctor (and my pharmacist) didn’t say a thing when I started statins last year. I’m going to have to bring this up next time I see her. I read about grapefruit here on some other thread and stayed away, but she should have mentioned it