Simvastatin & Grapefruit: Fatal Interaction?

[Jimmy Snyder]

Man am I angry. I was just perusing the instructions that come with my medicine, simvistatin, and it says I shouldn't drink more than 1 quart of grapefruit juice a day or eat large amounts of grapefruits. My doctor never mentioned this. I went on the web and found out that the interaction between simvistatin and grapefruit is dangerous in the extreme. Grapefruit blocks the action of the drug which then builds to dangerous and even fatal levels in the body. I eat one a day most days. That is, I did. Now I have to go to my doctor and explain to him why I am switching to another doctor. I'm off grapefruit for the rest of my life.

 

[Monique]

Grapefruit does that to many drugs. You should ALWAYS read the instructions of the drugs you are taking, you should also ALWAYS check whether the instructions have changed between uses. I'm glad you did read the package insert.

 

[lisab]

What are you doing eating grapefruit, anyway ? Anything that you have to coat in sugar to make palatable, you shouldn't be eating.

 

[hypatia]

You could be ask to switch to non-statin cholesterol-lowering medication. The risk of statins and Grapefruit is very well known, your Doctor AND/OR Pharmacist should of mentioned it to you.

 

[zoobyshoe]

What are you doing eating grapefruit, anyway ? Anything that you have to coat in sugar to make palatable, you shouldn't be eating.

I never put sugar on grapefruit. I love it as is. People grow it in their backyards here, and you will never taste such wonderful grapefruit as that if you're limited to store-bought.

 

[Moonbear]

As a grapefruit lover too, I would also be inquiring about switching medications.

Ideally, both doctor and pharmacist should have informed you of the interactions, but definitely the pharmacist should explain any common food interactions with a new prescription. I would choose a different pharmacy before choosing a different doctor.

 

[Evo]

One of my medications supposedly can't be taken with grapefruit, it can be fatal. I drink red grapefruit juice all of the time, I'd been taking the medication and drinking large amounts of grapefruit juice almost daily for 10 years before I found out.

 

[Jimmy Snyder]

What are you doing eating grapefruit, anyway ? Anything that you have to coat in sugar to make palatable, you shouldn't be eating.

My mother puts sugar on grapefruit, and that's how she served it to me when I was a child. But now I eat them plain, except that I don't eat them at all. After I change doctors I will ask for a substitute medicine that allows me to eat them again. As for my pharmacist, I don't have one, I get my meds in the mail.

 

[Evo]

My mother puts sugar on grapefruit, and that's how she served it to me when I was a child. But now I eat them plain, except that I don't eat them at all. After I change doctors I will ask for a substitute medicine that allows me to eat them again. As for my pharmacist, I don't have one, I get my meds in the mail.

I've never had a doctor ask me if I eat grapefruit and they all know I take that medication.

When you change doctors over this, don't mention that you eat grapefruit. They will ask you what meds you are on. I guarantee you that they will not ask you if you eat grapefruit. Are you going to keep searching until someone asks you about grapefruit? I'm serious.

Are you going to get rid of the company that sends you the medication? Do they include warnings about the grapefruit with the medication?

You would not believe how many known interactions there are that are not mentioned.

 

[Jimmy Snyder]

I've never had a doctor ask me if I eat grapefruit and they all know I take that medication.

When you change doctors over this, don't mention that you eat grapefruit. They will ask you what meds you are on. I guarantee you that they will not ask you if you eat grapefruit. Are you going to keep searching until someone asks you about grapefruit? I'm serious.

Are you going to get rid of the company that sends you the medication? Do they include warnings about the grapefruit with the medication?

You would not believe how many known interactions there are that are not mentioned.

The point is not what he asked me. If I said no, how would he follow up? Rather the point is that he should have told me avoid grapefruit while taking this medicine regardless of whether I had ever eaten one in the past. I can't dye my hair red because some rat died after having 5 gallons of the stuff poured down its throat, why should I be allowed to eat grapefruit? When I change doctors, I will not wait for him or her (but at my age, it will definitely be him) to ask me anything. I will make it clear to him what I expect up front. Funny thing is, when I am in the hospital I ask everyone who comes near me who I am and I don't give up until I hear my name. Most of the personel seems to be aware of what I am doing. As for my man, he did include warnings, I just didn't read them. That's my fault and won't happen again, but it does not excuse the doctor.

Surely there is some board that oversees doctors. I have every intention of finding out tomorrow where they are and to complain about this episode.

 

[Evo]

Surely there is some board that oversees doctors. I have every intention of finding out tomorrow where they are and to complain about this episode.

jimmy, have you ever had a doctor that prescribed a medication, then whipped out the drug interaction page and read it to you? It doesn't happen. I think you're over reacting.

And your "man" with the drugs, did he slap a "don't eat grapefruit" warning label on the bottle or just include the flyer? I think you should be reporting the pharmacist, or whatever they are, that send you the drugs. It's a rare reaction.

 

[Jimmy Snyder]

jimmy, have you ever had a doctor that prescribed a medication, then whipped out the drug interaction page and read it to you? It doesn't happen. I think you're over reacting.

My doctor knows all of the drugs I am taking and doesn't need to consult me concerning their interactions. This is an interaction between a drug and a food item. And a potentially fatal one.

 

[Evo]

My doctor knows all of the drugs I am taking and doesn't need to consult me concerning their interactions. This is an interaction between a drug and a food item.

I'm well aware of it, like I said, I found out 3 years ago I am taking a daily medication that has a possibly fatal reaction with grapefruit, been taking them both together for over 10 years, no problems. It's very rare. I'm probably more likely to be killed by a meteor.

Also, you just said that your doctor doesn't need to consult you about interactions, so why are you complaining?

I can understand you being upsaet if you just read something on the internet. Do you seriously drink more than a QUART of grapefruit juice a day? Even I only have a couple of glasses.

 

[Proton Soup]

maybe the risk isn't that high. do you actually eat large amounts of grapefruit, or do you eat a normal amount?

 

[Evo]

Here are the real risks of grapefruit and your medication. You can relax jimmy. Your medication seems to have the least side effects.

Statins
Atorvastatin (Lipitor), lovastatin (Mevacor), simvastatin (Zocor)
Increased plasma concentration may cause headaches, gastrointestinal complaints, hepatic inflammation, and myopathies (e.g., rhabdomyolysis).21–24

http://www.aafp.org/afp/2006/0815/p605.html

 

[mcknia07]

Well, as someone who works in a pharmacy, I know, that you should ask a pharmacist (any will do), that if you normally have a grapefruit, should you stop it cold turkey. Some meds, that will do more harm if you stop, if your body is used to it. Just ask before you do anything. If nothing else, I could inquire at my job...

 

[Proton Soup]

Here are the real risks of grapefruit and your medication. You can relax jimmy. Your medication seems to have the least side effects.



http://www.aafp.org/afp/2006/0815/p605.html

that last effect is pretty severe, but perhaps it isn't common

 

[Jimmy Snyder]

I have already lodged a complaint with the Board of Medical Examiners. I will abide by their decision concerning the seriousness of this matter. However I will certainly change doctors in any case. It seems I was unclear on the following points, so I will try to amplify.

1. Doctors are aware of interactions between one prescription drug and another and so are pharmacies. Until now, I have relied on them to avoid dangerous cocktails because they are able to do so. I will no longer, but that doesn't change the fact that the doctor controls the ingredients of the cocktail and can do the interaction matrix without telling me about it. But when it comes to interactions between prescription drugs and non-prescription drugs, or food items, the doctor cannot know what the patient is eating and cannot assume that the patient knows the interaction matrix. In my opinion they MUST tell the patient what interactions of this kind exist and I can't imagine why that isn't a no brainer. The fact, if indeed true, that it isn't commonly done does in no way molify me.

2. I have been taking the drug for about 9 months already. Today I read the warning for the first time. It says:

DO NOT DRINK LARGE AMOUNTS OF GRAPEFRUIT JUICE (greater than 1 quart daily) or eat large amounts of grapefruit while taking this medicine.

Emphasis theirs. I do not drink that much juice. In fact, although I had a 4 oz. glass yesterday morning and an 8 oz. glass this morning just before I read the warning, I do not normally drink juice at all. There are good reasons to avoid fruit juices in favor of the fruit itself. I eat a grapefruit a day when I can get them, rarely two. I still don't know how many is 'large amounts'. While surfing the net looking for information I have found all manner of warnings including one that said that I should not have any grapefruit and the drug at the same time. I am not unaware that I have not been under a great danger from my behavior. My issue is not that I almost died, that is indeed ridiculous. It is that I had no clue what I was doing.

What is more, as I implied earlier, many products are removed from the consumer market because some rat died after taking obscene amounts of it. If red dye #4 was taken off the shelf for everyone, then why wasn't grapefruit taken off the shelf for me? Let me be clear, if there is a known interaction between the drug and large amounts of grapefruit, then why wasn't a decision made at a high level to disallow the drug to be taken with any grapefruit at all? Why aren't there clear instructions telling doctors to tell their patients no grapefruits, no exceptions, no interactions, no injuries, no deaths, no lawsuits. They do it with everything else.

 

[Evo]

that last effect is pretty severe, but perhaps it isn't common

I have taken a large number of medications that have side effects of "sudden death" listed.

If we all went around fearing every possible thing that could affect us, we'd live in a 1950's fallout shelter eating only, well, even milk and eggs can kill you, so I don't know what you'd eat.

Listen to advisories, but don't let it freak you out. Retain some common sense.

 

[Proton Soup]

I have taken a large number of medications that have side effects of "sudden death" listed.

If we all went around fearing every possible thing that could affect us, we'd live in a 1950's fallout shelter eating only, well, even milk and eggs can kill you, so I don't know what you'd eat.

Listen to advisories, but don't let it freak you out. Retain some common sense.

yes, and it's likely the muscle cramps and pain would show up long before rhabdo. i do agree and think our OP is freaking out just a bit.

 

[Frame Dragger]

Well now, I think the point to remember here is "A quart or more per day". They're not saying you're going to drop dead after your first cup of juice. What happens, sadly, is that over time the grapefruit juice and statins compete for enzymes, stress the liver, and damage is done.

This happens, with a LOT of medications. Take most acid reducers, and you'll have issues with Iron. Take an MAOI, and you really CAN drop dead from a slice of old cheese.

The OP may be very alarmed, but he should be although the risk to his health based on his description is negligable. The difference between legal boiler-plate and medically established fact is not something for laypeople. It CAN be determined, if you know how to read a study and evaluate it for quality. That is in fact why GPs, AND the pharmacist should be giving verbal warnings.

Ah, and lots of medications have "drop dead" warnings for 2 reasons. The most common is that ANYTHING can cause an allergic (anaphylactic) reaction in a person. Take IV Iron infusions for instance. They're not uncommon for a variety of common causes of IDA (Iron Deficient Anemia), and when you get one there WILL be someone with a crash -cart waitng. Iron isn't dangerous, but some people go right into anaphylaxis, which is pretty close to "dropping dead" short of cardiac arrest.

On THAT fun note, there are the "hardcore" drugs that don't cause problems, but if you are unfortunate enough to have a long QT interval, or some other arrythmia, it's lights out. Most antipsychotics will drop someone with Long QT if you give it to them often enogh, and it's a Russian Roulette setup each time.

Bottom line: If there is an effect, there is the possibility of adverse reactions. That chance is usually poorly evaluated (as both too risky, and not risky enough) by most non-medical professionals, and plenty of MDs. If you're really concerned, double check your regimen with a pharmacologist... but to be frank, the combo of Simvastatin and Grapefruit would cause a LOT of other symptoms before "death".

Generalized pain would be a big giveaway, and the jaundice and slow liver failure would be another hint.

Finally, there are people who lack certain cytochromes and fail to produce enough of enzymes that are used in multiple metabolic processes. Those people, who might already be at their body's limit with a grapefruit, are overdoing it with the statin. There would be warning signs however as Proton Soup mentioned. There always are unless sudden death really = SUDDEN.

 

[robertm]

This seems to be the main culprit in the grapefruit's interactions with drug metabolism:

These results indicate that BG [Bergamottin], the primary furanocoumarin extracted from grapefruit juice, is a mechanism-based inactivator of P450 3A4 [in the small intestine]. BG was also found to inhibit the activities of P450s 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes.

http://pubs.acs.org/doi/abs/10.1021/tx970192k"

An incomplete (but good) table of substrates, inhibitors, and inducers of the cytochrome p450 III-A-IV enzyme:
http://en.wikipedia.org/wiki/CYP3A4"

Based on four different in vitro approaches, namely 1) correlation analysis, 2) chemical inhibition, 3) immunoinhibition, and 4) metabolism by recombinant human P450, it is concluded that CYP3A is the major enzyme subfamily responsible for the metabolism of SV [simvistatin] by human liver microsomes.

http://dmd.aspetjournals.org/content/25/10/1191.abstract"

Well there's your problem right there.

I get the feeling that you probably already disliked your doc., but now you have an actual reason to get rid of him. Be mindful of what you ingest, and good luck with your cholesterol!

 

[Pythagorean]

Doesn't grapefruit enhance the effect of medication if you don't overdo it to where your medication is too powerful?

 

[robertm]

Doesn't grapefruit enhance the effect of medication if you don't overdo it to where your medication is too powerful?

This is messy, but gives a good overview:
http://en.wikipedia.org/wiki/List_of_drugs_affected_by_grapefruit"

Obviously, the interactions favourable for recreational use of opiates and benzodiazipines are of the most common interest.

 

[Proton Soup]

Doesn't grapefruit enhance the effect of medication if you don't overdo it to where your medication is too powerful?

see the link that robertm posted:

This interaction is particularly dangerous when the drug in question has a low therapeutic index, so that a small increase in blood concentration can be the difference between therapeutic success and toxicity. Grapefruit juice only inhibits the enzyme within the intestines, not in the liver or elsewhere in the body, and does not impact injected drugs. The degree of the effect varies widely between individuals and between samples of juice, therefore it cannot be accounted for a priori.

from what i remember of the time i experimented with grapefruit, the effect is mostly all on CYP enzyme in the intestine, and not the liver, with the result being higher blood levels of the ingested drug when you also consume grapefruit. so, grapefruit results in a higher effective dose for a given orally-administered drug.

unfortunately, there's not much going on in the liver, so if you want to manipulate CYP there, you're out of luck. all it ever gave me was a bellyache.

 

[EnumaElish]

I did a google search, which found this document: http://www.healthcentral.com/peoplespharmacy/pp_guides/PDF/gfruit02.pdf

 

[Ivan Seeking]

Shouldn't this be in Medical Sciences?

The name of the thread led me to believe it was some kind of joke.

 

[Frame Dragger]

Shouldn't this be in Medical Sciences?

The name of the thread led me to believe it was some kind of joke.

It still could be. I can think of a number of humorous ways to use a grapefruit with lethal results. Killer Grapefruit... priceless... :zzz:

 

[Jimmy Snyder]

Shouldn't this be in Medical Sciences?

It wasn't intended to be, but it has been hijacked into something that probably should be.

The issue I brought up was not about the specific benefits and harms of grapefruit, nor the exact process by which it benefits or harms. It was the denial of what I consider crucial information by a doctor to his patient. The consensus is that since grapefruit does not interact with simvastatin harmfully unless taken in large amounts, it isn't necessary to inform any particular patient about the problem, nor even to ask whether the patient already takes a dangerous amount. This matter being settled, the conversation strayed to one of Medical Science.