This is the sort of exchange that makes the archive worth searching.
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Practice · Interactions · continued
Grapefruit: why this class is not the class that cares posts 31–60
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
Bramley, post #6: Picking up post #5: that is the part I would want checked first. The useful distinction on grapefruit is between what was measured and what was inferred from it. Both end up in the same sentence and only one of them has error bars. Go to post
A pharmacist can answer most questions in this subcategory in a few minutes with access to a proper interaction database, and that access is the thing a forum does not have.
Post #32 answers the question as asked. The question underneath it is different.
Alcohol: no absolute contraindication but it raises gastrointestinal irritation risk and this drug class already does that. The conservative position during titration is to limit it.
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The number people quote for grapefruit is a central estimate presented without its interval, and the interval is wide enough that the estimate is nearly uninformative on its own.
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A supplement is a drug for interaction purposes, and the fact that it is sold without a prescription tells you nothing about whether it interacts. The paperwork is usually worse rather than better.
Noting that the question and the thing people usually mean by it are different.
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a.vukovic, post #14: Delayed gastric emptying is the mechanism behind most of the plausible interactions in this class: anything whose absorption depends on how quickly the stomach empties can behave differently. Go to post
Anticoagulant questions come up regularly and are the clearest case for professional advice rather than discussion, because the consequence of being wrong is not gradual.
Everything in post #35 holds. The case it does not cover is the one I have.
Grapefruit was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.
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k.vanhecke, post #28: Fine by me. I had wanted a stronger conclusion and there is not one available. Go to post
Adding the measurement that post #36 says would settle it.
Grapefruit is one of those subjects where the general answer and the answer for a specific case diverge, and the thread will go in circles until someone says which one is being asked for.
s.beaulieu, post #38: Everything in post #35 holds. The case it does not cover is the one I have. Grapefruit was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread. Go to post
Insulin and sulfonylureas are the interaction that the labelling in this class flags most explicitly, because the risk is additive glucose lowering. That is a prescribing question and not a forum question.
The interesting part of this is the exception, and I do not understand the exception.
Collapsed as off-topic by two members at trust level 3 or above
On post #39 — agreed on the reasoning, with one qualification.
Careful with the language on grapefruit. "Not detected" and "not present" are different findings and the first is a statement about the method.
The most defensible general position in this subcategory: identify the plausible mechanism, check whether it has been studied, and where it has not, say that rather than filling the gap.
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r.danquah, post #17: Taking post #14 at face value and following it one step further. On grapefruit, I would rather understate and be corrected upward than overstate and be quoted. That is a house style here and it is a good one. Go to post
Posting my grapefruit numbers with the method attached so they can be discounted properly. Uncontrolled, unblinded, and collected by someone who wanted a particular answer.
Post #43 is right about the mechanism and I think understates the practical bit.
Alcohol: no absolute contraindication but it raises gastrointestinal irritation risk and this drug class already does that. The conservative position during titration is to limit it.
I checked the source rather than the summary, and they differ.
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OTeixeira, post #33: Post #32 answers the question as asked. The question underneath it is different. Alcohol: no absolute contraindication but it raises gastrointestinal irritation risk and this drug class already does that. The conservative position during titration is to limit it. Go to post
The practical version of grapefruit is three sentences long. The rigorous version is three pages and reaches the same conclusion with the conditions attached.
PharmNotes_Whitfield, post #24: Post #21 is right about the mechanism and I think understates the practical bit. Where a published interaction study exists it usually reports an area-under-curve ratio, and that number is far more informative than a yes-or-no answer. Someone should write this up properly, and it should probably not be me. Go to post
I had written a reply contradicting post #43 and deleted it. Here is what survived.
On grapefruit the community has more anecdote than the confidence in this thread implies, and I include my own contribution in that.
Confirming post #47 from a second method, which matters more than confirming it from a second person.
A supplement is a drug for interaction purposes, and the fact that it is sold without a prescription tells you nothing about whether it interacts. The paperwork is usually worse rather than better.
That much is documented. The rest is how I have interpreted it.
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Collapsed as off-topic by two members at trust level 3 or above
The arithmetic in post #47 is right; the assumption feeding it is the part to check.
I have been on both sides of the grapefruit argument in this category within eighteen months, which should tell you how strong the evidence for either side is.
a.batista, post #11: The version of grapefruit that I was taught turned out to be a teaching simplification. Useful, and not true in the way I had assumed it was. Go to post
Answering the question post #48 raises rather than the one it answers.
I keep a log for grapefruit specifically because my memory of it turned out to be systematically wrong in one direction. Six weeks of notes cost nothing and settled it.
s.mbeki, post #23: Coming back to post #21, because the follow-up matters more than the original answer. The honest answer on grapefruit is that it depends, and the useful part is the list of what it depends on. Four items, in rough order of how much they matter. Most people get the first two right and then argue about the fourth. Go to post
A pharmacist can answer most questions in this subcategory in a few minutes with access to a proper interaction database, and that access is the thing a forum does not have.
I would put the burden of proof on the interesting explanation, not the dull one.
Two things can be true about grapefruit at once: the mechanism is plausible and the evidence for the size of the effect is thin. Most of the argument here is people defending the first against attacks on the second.
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Adding the measurement that post #54 says would settle it.
Before the thread moves on from grapefruit — what is the sample size behind the claim? I am not being difficult; I have seen the same figure quoted from an n of four and from an n of four hundred.
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Post #52 describes the usual case. This is about the unusual one.
Where a published interaction study exists it usually reports an area-under-curve ratio, and that number is far more informative than a yes-or-no answer.
A single observation, in a thread that deserves better than single observations.
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journalclub_wren, post #30: Adding the measurement that post #29 says would settle it. Grapefruit is a question about a distribution, not about a value, and treating it as a value is what produces the confident wrong answers. Go to post
Anticoagulant questions come up regularly and are the clearest case for professional advice rather than discussion, because the consequence of being wrong is not gradual.
I changed my mind about grapefruit after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens.
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mi.almeida, post #59: I changed my mind about grapefruit after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens. Go to post
What would change my mind on grapefruit is a second dataset collected by someone with no stake in the first. Until then I hold it loosely and I would rather say so than pretend to more.