Prescription drugs and grapefruit a 'deadly mix' (2012) | Hacker News Reader

Prescription drugs and grapefruit a 'deadly mix' (2012)

nhs.uk

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This killed my friend's dad. He was on a bunch of heart drugs and had a pacemaker and everything, but was generally stable. One day, grapefruit comes up in conversation with his doctor, who sternly advises him "never eat grapefruit, it'll mess with your meds!", so he stops eating the grapefruit he'd been having for breakfast every morning for years.

Which promptly hoses up the finely-adjusted dosages, his symptoms suddenly get real weird, the situation spirals out of control, and he's dead in 4 days.

Doctors, please don't rush out of the room. Take time to talk to your patients, and take twice as much time to listen to them. I'm sure he would've mentioned that detail if he'd had time to find the English words.

Doctors want you in and out of the room in 5 minutes or less so they can pull the insurance money dispensing lever again.

The last physician I had any respect for was my own pediatrician and I had consulted him on various issues having gone through several GPs that got even simple diagnoses disastrously, hilariously wrong. Such as telling me the tiny red lump in my finger was an anthrax infection and notifying the health department when it was really a small benign vascularity that was removed in a fifteen minute procedure.

Since my pediatrician retired I just do all my own medical research and order my own lab tests. The advantage I have is that I have all the insight into my own body, history, and habits that no doctor these days ever takes the time to find out. You're just a money pinata. Thank you, here are some antibiotics for an unspecified pathogen I didn't culture, Alisha will see you at checkout. Examining the patient? Ain't nobody got time for that.

How do you order a lab test on your own?

In the US there are surprisingly few barriers to this, an extreme rarity in our healthcare system.

https://questdirect.questdiagnostics.com/

https://www.walkinlab.com/

https://requestatest.com/how-it-works

https://www.healthonelabs.com/

https://www.directlabs.com/

I have no affiliation with any of the above, they were just the first to pop up on Google (there are plenty more).

Find a local lab, ask about submitting a lab, collect then deliver samples. There isn't anything special that says a blood test has to be requested by a doctor.

A lab is rarely going to advertise to consumers directly (some startups do this with mail in tests), but a smaller one will be happy for the bit of extra business.

Not necessarily true. In many states if a doctor does not request it your insurance has no obligation to pay. That doesn’t mean you can’t get it done, but you’ll be spending hundreds of dollars out of pocket for it.

Also, everywhere I’ve ever lived labs have been a very commercial business. They advertise constantly about it...

That's a malpractice case. The doctor gave advice that he knew was potentially fatal.

> Take time to talk to your patients

I agree that most doctors rush things (for whatever reason). But what does it have to do with this case ? the advice was solid- stop eating grapefruit.

Did you read the full comment you're replying to? The person who died was told this exact advice - stop eating grapefruit, and that lead to them dying in 4 days.

I did, and according to theory he should have gotten better after stopping eating grapefruits- how could a longer talk with a doctor help in this case ?

They had spent what I’m sure is many visits finely honing the dosages of his various medications. The efficacy of those medications combined with grapefruit was different than it would have been without grapefruit.

Suddenly stopping grapefruit caused a drastic shift in the levels of those medications in his system and caused catastrophic problems.

In short: it works both ways. Grapefruit screws with levels. If your levels are tuned to a non-grapefruit diet you shouldn’t start eating it. If they are tuned to a grapefruit diet you shouldn’t stop eating it.

Either way his doctor should have spoken to him when he started the drugs and discussed the grapefruit factor, and absolutely should have been mindful of whether or not his patient had been eating grapefruit all along when telling him to stop eating it. It’s the same as being on another medication, he shouldn’t have discontinued it immediately, he should have tapered off.

Sounds like the guy was over medicated, but eating grapefruit daily. As far as I understand it, grapefruit binds to the drugs, reducing the level of available drug in your blood. So when he stopped eating grapefruit his levels spiked. Its unfortunate but when his doctor said "hey don't eat grapefruit it'll screw with your levels." The guy _really_ _really_ should have said, "oh yeah doc I've been eating grapefruit every morning for breakfast," which would have started a much larger conversation.

My personal experience as someone on a lot of blood pressure medication has been that all my doctors have been very clear and up front with me about not eating grapefruit while on that kind of medication. When I asked why they were happy to explain the interactions. And it's not just blood pressure medication. The same type effect happened with my other meds too.

Exactly. That's the conversation that should've happened.

But English was the patient's second or third language, learned late in life, and he was never particularly fluent in it. Enough that they didn't feel like calling a translator, but not enough to really communicate as well as should've happened.

Waiting for him to come up with words didn't fit with modern medicine's idea of the doctor seeing another patient as promptly as possible, so instead, he's dead.

This bit my brother once, on a trip to visit our grandparents. Grandpa would eat a half grapefruit every morning, believing that the acidity would alkalize one's system in response and lead (along with frequent alternative chelation treatments) to better health. We didn't drink the chelation shakes, but we did eat the grapefruits, since they were there and prepared.

Over the two-week visit, my brother got harder and harder to be around - he'd always been surly, and he struggled with grandpa's wife, but we'd never experienced the level of emotional turmoil he went through on that trip. He self-harmed, sliced his arms up deeply. I stitched him up with the sewing kit that the resort had mercifully left in the room for us, and we kept the wounds dressed with neosporin until they healed.

The next stop on the trip was a visit to grandpa's wife's sister, a professor of neuroscience. She just happened to mention the interaction between antipsychotics and grapefruit, and it was like a light went on in my brother's mind. He stopped eating grapefruit and returned to his usual mental state within a few days.

Did none of the doctors prescribing the antipsychotics highlight and caution against eating grapefruit - hopefully to not consume alcohol either?

I can't speak to his interactions with any doctors. I imagine he forgot. This was before he was 21, so alcohol wasn't an issue yet.

One of the many pitfalls between doctor-patient relationship. Thank you. Hope he's continued to have relative stability.

Interesting to see this now. As a teenager I experimented with DXM (https://en.wikipedia.org/wiki/Dextromethorphan) as a hallucinogen. You could buy it in powdered form over the internet for a while, or one could just take corricidin pills or find certain cough syrups that didn't have acetaminophen. Anyways, it was well known on usenet/IRC at the time that drinking grapefruit juice prior to ignesting the drug would enhance its effects.

I had just come out of the peak of an acid trip so intense that I was in the fetal position under my covers. 1-2 hours had passed but it felt like an entire day. And it took me 10 minutes just to finally message my friend the profound admission: "im trippin".

I was pretty hungry after all this and glad the peak was behind me. Got a grapefruit out of the fridge. Wasn't even halfway through when I found myself back in the peak. Had to crawl back into my bed where the curtains were closed and endured another 20 minutes of that.

Grapefruit + <drug> has always been the source of superstitious arguments in uni among my drug-using friends. Does it enhance the effect? Kill the effect? Do anything at all? But my acid experience confirmed one pairing beyond all doubt.

I vaguely remember grapefruits being Hunter S Thompson's favourite fruit. I don't think it was for the taste.

And your experience matches mine. Washing down MDMA with grapefruit juice definitely makes it more intense.

Inhibiting CYP3A4 should definitely increase LSD AUC, but it can't magically conjure more of a substance out of thin air after it's all already entered your bloodstream - only slow down breakdown. Albeit the apparent effect would be the former, if ingested beforehand and/or dealing with something with very slow uptake and high first-pass metabolism.

In any case it's not something that plays out so quickly.

Waving in and out of tripping balls a couple hours in sounds pretty par for the course, I'd say :)

Perhaps changing the ph of the bloodstream could also have an effect? Would presumably increase solubility? Lots of lore around citrus with psychedelics, seems plausible but would be nice to have more research on the mechanism.

If the pH of your bloodstream goes out of whack enough to impact solubility, you’re long dead.

Thanks, you are right. Looks like blood pH must remain between 7.35 and 7.45 or else serious negative effects occur. Solubility change would be negligible.

Not related to grapefruit but moving to North Carolina for college in 2010 re-ignited my love affair with DXM in the form of Vicks 44 Berry Blast, which was about 300mg of DXM in a refreshingly horrible syrup form factor with 0 guafenesin, acetominophen or any other things that would get in the way of pure rolling.

Coupled with whatever substance du jour that college me was able to lay hands on, DXM was guaranteed to have me stumbling and hallucinating like the true futureless human I aspired to be, for the low low price of $7.65.

So, hats off to the NC state legislature for giving me some cheap thrills through college just outside my dorm room, while the state liquor store was a few miles away. You saved my liver, non-sarcastically, and allowed me to experience first hand the precipice of drug culture so I could willingly walk away from it based on personal exposure.

I also can't stand the sight of cherry flavored anything anymore :)

>You saved my liver, non-sarcastically

FWIW, it's not particularly difficult to cause liver damage with dextromethorphan at recreational dosages

Citation needed. DXM is often packaged with Tylenol, which I believe explains all the liver failure cases we've seen regarding DXM abuse.

I'd be curious to hear what medical evidence is available that could provide a dosage and frequency that specifically points to DXM and not anything else.

Back when I was on the forums at that time, we were much more worried about frying our minds with dosing 4000mg and disappearing for days at a time into the strangest and scariest hallucinations you could imagine.

Uhhhhh as far as I know, acetaminophen is the damaging agent, not dxm; it's often packaged with it for pain relief in cold/flu medications... but dxm itself doesn't damage the liver. Dxm has been shown to do some weird stuff with Olney's Lesions, but doesn't really impact the liver.

As far as I know, Olney's lesions have only ever been shown at heroic dosages in mice.

It's also worth noting that DXM is being studied in research as an antidepressant. I'm aware of at least one company working on it in combination with wellbutrin: https://axsome.com/axs-pipeline/about-axs-05/

DXM has a pronounced antidepressant effect that lasts for days after a recreational dose. Users refer to it as an afterglow instead of a hangover. This effect is fairly well known but not currently commercialized. It's also a similar drug to ketamine, which is also being used as an antidepressant in medical settings now.

From my own anecdotal experience, I'd probably have killed myself in my early 20s without DXM to give some relief. Sometimes I'll still grab a bottle of it if I'm in a particularly dark place. It's sometimes a pleasant experience, sometimes an unpleasant one, but it always lifts depression for a few days.

From what I've been able to understand over the years from the literature, nobody's died on DXM alone without taking extreme doses (anything over 500mg is crazy IMO). Some people have died from taking products that contained other active ingredients. CCCs were common before people realized the antihistamine overdose is harmful. Tylenol is common in those products too and could be used by someone uninformed, though that's also true for most painkillers. Even in extreme cases of daily high dosages (which doesn't make sense because of tolerance, but people are crazy), organs don't seem to be harmed.

Obviously chugging cough syrup has a questionable reputation at best, but we'll be seeing more people become aware of it in the next few years as drugs get mixed with DXM and patented as anti-depressants.

There's also at least one company on Amazon selling 500mg+ bottles that look like they're "4 hour energy"-sized, with DXM as the only active ingredient, complete with headshop-aesthetic packaging: https://www.amazon.com/Cough-Suppressant-RoboCough-2-Pack/dp... Questionable for sure, but definitely less sketchy than the extractions and powders of years ago. I feel like I've seen less about DXM as cannabis has become more legal and as more odd chemicals, both legal and illegal, have become easier to order online.

edit: just to be clear, I haven't tried that product on amazon, I was just amazed to see that it exists and has such positive reviews.

DXM is really strange. Not to mention the robo walk.. got in big trouble when I was a teenager on that stuff. Absolutely impossible to hide, physically at least.

I love you guys.

Similarly, piperdine in black pepper can function as a bioavailability enhancer

https://www.ncbi.nlm.nih.gov/pubmed/21434835

I read an interesting online report that claimed co-administration of black pepper and certain essential oils would produce psychoactive effects.

Oooh I read that they use this with tumeric to enhance its absorption. I wonder if grapefruit would work similarly.

Interesting! I found this thread which claims that curcumin + black pepper can function as a reversible MAOI, similarly to caapi or harmala ayahuasca admixture plants.

https://drugs-forum.com/threads/curcumin-is-an-effective-ant...

I've been taking turmeric for an inflammatory issue, will try adding pepper, thanks!

I might have expected colchicine (https://en.wikipedia.org/wiki/Colchicine) to be on the list.

It's a fairly harsh drug with a narrow therapeutic window. Getting the right dosage is already hard enough, as there are some unpleasant (and common) side effects, and it can also be pretty dangerous to your health. Add something like grapefruit that throws off the concentration, and things get that much worse.

EDIT: This HN story link was updated. The list I was referring to above is the old link: https://en.wikipedia.org/wiki/Grapefruit–drug_interactions

I take atorvastatin for high cholesterol; it says don't eat grapefruit on the side of my medication bottle. I never really thought about why, but this gives me more reasons to avoid it. Although now I have a huge craving for grapefruit juice, of course.

Then read this article instead: https://www.ncbi.nlm.nih.gov/pubmed/26299317

Thank you. I've been skipping graperfruit juice for years.

Did you ever find out why you have high cholesterol? Are you above or under 30?

I wonder why it took the medical profession so long to become aware of the effect. Piperonyl butoxide, another cytochrome C inhibitor, has been used as synergist in insecticides since before the war, so it should have occurred to someone that the plentiful polyphenols in citrus juice could act as cytochrome C inducers/inhibitors and would have a measurable influence on the pharmacokinetics of stuff.

Just because the article says that the healthcare community is ignorant of it, doesn’t mean that it’s ignorant of it.

We had to memorize major CYP4503A4 inducers and inhibitors for step exams back when I was in med school, and memorized metabolic pathways and involved cytochromes for most major drugs.

Granted, most docs don’t remember all the details long out of med school (because that’s literally what pharmacists are -for-), but we retain the broad brushstrokes.

Ain’t new. Just editorializing bs.

Yeah, hasn't "don't eat grapefruit while on birth control" been common advice for years?

Yes, also on medication for high-blood pressure.

(luckily I never had a great liking for grapefruit)

I sometimes forget because it's not something that I regularly have. I just have to spend a few moments on my phone before buying certain fruits.

There was a wave of grapefruit flavored beers that really needed to have that warning on it but didn't.

I think “the war” refers to World War II (curious name for it!) and this person still has a point, unless you went to med school before 1990. The wiki[0] says that the effect was discovered in 1989, and lots of the referenced literature is from 2002/2003.

[0] https://en.m.wikipedia.org/wiki/Grapefruit–drug_interactions

It's quite normal here to refer to it as the war. "Back in the war..." :)

I distinctly remember being told to avoid grapefruit with certain antibiotics in the early 90s. I know that, in about 2000, my father was told to avoid grapefruit all the time because he was taking drugs for gout. He loved grapefruit and complained bitterly about the restriction.

If you've had a liver transplant, grapefruit is on the list of things that you can never eat again -- it messes with the anti-rejection drugs that you have to take to suppress your immunological system.

Caffeine is on the list.

So a breakfast of coffee and grapefruit is a medically proven stimulating start to the day?

Sadly, no.

>One study, by Maish and colleagues in Pharmacotherapy 1996, looked at whether grapefruit juice increased caffeine effects and found little or no difference in blood concentrations and blood pressure when caffeine was given with and without GFJ. Other research has confirmed these results. Since specific enzyme systems most often metabolize similar chemicals, one would not necessarily expect GFJ to affect other stimulants, but this is far from conclusive.

https://erowid.org/ask/ask.php?ID=2726

IIRC naringin has an indirect effect on coffee, where it inhibits an enzyme that is involved in metabolizing caffeine. So the outcome is that the effect of your coffee lasts a lot longer, instead of being more potent.

Edit: Now that I go looking again, there is also evidence against this conclusion: https://www.eurekalert.org/pub_releases/2003-04/aps-rsm04090...

It would certainly be a horrific jolt to your taste buds... geish.

Alcohol? In student days, I was always fond of a greyhound: vodka and grapefruit juice. Placebo effect, or diminished liver capacity?

My hay fever medication (called Teldanex in Sweden) was withdrawn from the market in 1998 due to some fatalities when combined with grapefruit. So it must have been well known long before 2012. I remember feeling quite lucky I wasn’t into that particular fruit... :P

Also, I know that *mycin antibiotics can decrease liver metabolism of statins, and increase their side effects. In particular, rhabdomyolysis (muscle damage).[0]

So I suspect that grapefruit isn't the only issue. In that there may well be interactions among the drug classes listed.

0) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006404/

And yet it never seems to get enough coverage. The last time I was prescribed something important, I had no idea I wasn't supposed to have grapefruit or marmalade with Seville oranges. Luckily it's not my usual fare. The leaflet did have all sorts of other warnings though, like even for St. John's Wort. I only found out by a chance comment from a different physician.

I usually Lemon Tek when I take psilocybe: https://www.mushmagic.com/blog-magic-mushroom-lemon-tek-a-wa...

That's different, that converts the psilocybin to psilocin - something that would go on in your stomach anyway. Adding lemon gets that step out of the way so it all hits you faster.

Shouldn't there be a warning label in the Grapefruit section of supermarkets?

No, because the warning comes with the medecine

I've been scrutinizing my package leaflet for tamsulosin. No mention of grapefruit. Revision date October 2017.

The article links to research from 2012. I'm going to guess that the dangers turned out to be small and eat my grapefruit for breakfast tomorrow as planned.

https://www.webmd.com/drugs/2/drug-1592/tamsulosin-oral/deta...

Thank you, very helpful.

Its useful for getting the most bang for your buck ouy of expensive medications.

Hah I know right? I do wonder however, is there a use case for these furanocoumarins found in grapefruit? Perhaps it could make for more efficient drugs that could (potentially) be cheaper? Or perhaps doctors prescribing ludicrously expensive drugs (like the cancer drugs listed) could prescribe a lower dose and a grapefruit concentrate?

I wonder if grapefruit + reduced dosage could be as effective for primary effects, but reduce side effects for some drugs.

Would be interesting to find some research in this area: most of what I can find warns of increased side effects from maintaining constant dosage.

Interesting related info: "Seville oranges, (often used in marmalades), limes and pomelos also produce this interaction. Varieties of sweet orange, such as navel or valencia, do not contain furanocoumarins and do not produce this interaction."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589309/

I've heard it's best to avoid or reduce citrus intake while taking drugs.

I don't know why, but this could be why.

Also from the NHS website is this interesting 2014 report on grapefruit juice and diabetes. In the reported study, grapefruit juice was as effective at lowering blood sugar as metformin, a leading drug for type 2 diabetes. However, this report cautions about the results - the study was not carried out on humans, but on non-diabetic mice:

Could grapefruit juice protect against diabetes?

https://www.nhs.uk/news/diabetes/could-grapefruit-juice-prot...

I don't think that's how drug pricing works. According to this report's appendix G[1], manufacturing costs are 25% of price and they count after-release R&D as part of that (and don't count pharmacy margins).

Most generic drugs probably don't cost more than a few cents a pill to manufacture, assuming the pharmacy and manufacturer make a profit on it.

In other words, it's all in the R&D and compliance costs, which grapefruit couldn't help with.

And re: doctors prescribing a combination of active ingredients that hadn't had a pharma company spend a few billion dollars studying... well, just read this[2], about how some company is making big bucks selling $300 fish oil pill bottles that had a bit of FDA compliance work (and related studies) done about them because doctors would never prescribe the $30 pill bottles that weren't filed with the FDA.

[1] http://bvssp.icict.fiocruz.br/pdf/Pharmaceutical.pdf

https://slatestarcodex.com/2014/06/15/fish-now-by-prescripti...

Back when I was dependant on Valium, which was hard to acquire, it was a great way to rocket up the effects

LSD too apparently, so the wisdom goes.

I guess that might be medication depending how you view it.

One thing glossed over in these articles is that the impact is mostly on this enzyme as it exists in the intestines.

There’s less impact on this enzyme as it exists elsewhere in the body (primarily the liver).

I avoid grapefruit-anything. I’m on two pretty standard drugs, and they shouldn’t have any reactions, but I’d rather not take that chance anyway.

There's no need to guess; you can look up specifically whether CYP450 enzymes metabolize your medications (and its metabolites). If not then the answer is almost certainly that you're safe.

I don't know what the downvotes are about. I'm right. This stuff isn't magic. The mechanism of grapefruit-drug interactions is well-understood.

Here's a 2012 article from the NHS website on this topic which I think is more readable than the Wikipedia entry:

https://www.nhs.uk/news/medication/prescription-drugs-and-gr...

I'd even prefer the Erowid page : https://erowid.org/ask/ask.php?ID=2726

Thanks! Changed from https://en.wikipedia.org/wiki/Grapefruit%E2%80%93drug_intera...

Thanks - but also check out the “citrus genetics and interactions” section further down in the wiki, it’s fascinating.

Also Fresca is packed with grapefruit juice.

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