Wednesday, 4 June 2025

Farewell, beloved grapefruit.

I love grapefruit – specifically the pink variety; for the past few years I've been eating half a grapefruit daily and using the peel to brew me up my favourite tea. [Peel from half a grapefruit, two bags of Herbapol wild-cherry infusion, two bags of Herbapol raspberry-and-cranberry infusion, spiced up with a touch of ground cinnamon and ground cloves, in a large 660ml glass.] 

This has now stopped, given the nine-pills-a-day regime I'm on after my heart attack.

Grapefruit, eh? The first I heard of grapefruit and meds was at our school reunion; one of our classmates went on to be a part of the team that developed Viagra. He confided to us that half a pill is as effective as a whole one, and that a quarter of a pill washed down with grapefruit juice is also as effective as as a whole one. I am also hearing from people on medication for diverse medical conditions that grapefruit is to be avoided.

So I asked Google Gemini: "Taking the following pills, should I be eating grapefruit?" 

I listed the nine drugs one by one and received the following reply: "The most significant and potentially dangerous interaction for you is with Inspra (eplerenone). Consuming grapefruit with Inspra can lead to dangerously high levels of the medication in your blood, increasing your risk of hyperkalemia. Additionally, grapefruit consumption may significantly reduce the effectiveness of two other vital cardiovascular medications: Efient (prasugrel) and Roswera (rosuvastatin). These drugs are crucial for preventing blood clots and managing cholesterol, respectively. A reduction in their effectiveness could lead to suboptimal treatment outcomes and an increased risk of adverse cardiovascular events."

The recommendation was unambiguous.

"Given the strong interaction with Inspra, the following actions are strongly recommended: Immediately Cease Grapefruit Consumption: Given the critical and contraindicated interaction with Inspra (eplerenone) and the significant potential for reduced efficacy of Efient (prasugrel) and Roswera (rosuvastatin), the safest course of action is to immediately and completely stop consuming grapefruit or grapefruit juice."

So – given that the most significant and potentially dangerous interaction with grapefruit is Inspra, I re-read the leaflet enclosed in the box. No, not a single mention of grapefruit.

I ask Google to produce me a research paper about grapefruit and Inspra. The result is thorough and enlightening. In a nutshell:  "The primary mechanism underlying many grapefruit-drug interactions involves the inhibition of the CYP3A4 enzyme. Grapefruit contains specific compounds called furanocoumarins, such as bergamottin and 6′,7′-dihydroxybergamottin, which are potent inhibitors of the cytochrome P450 3A4 (CYP3A4) enzyme system." And: "CYP3A4 inhibition is potent and irreversible" Gulp! I've been taking Inspra and eating grapefruit for seven weeks! I am told to also avoid Seville oranges (the bitter ones that often feature in marmalade, and citrus peel in general, and to limit lime consumption. Sweet oranges and lemons are OK. And bergamot oranges*

Then I asked the AI to look at the Polish-language leaflet that comes with Inspra. It replies: "An examination of the Polish leaflet accompanying Inspra 25mg confirms that it does not explicitly mention avoiding grapefruit (grejpfrut) in its interactions, warnings, or contraindications sections. This can lead to questions for patients who may encounter conflicting information from other sources. Despite the absence of explicit mention of grapefruit, the Polish leaflet and the Summary of Product Characteristics (ChPL) for Inspra 25mg do include several crucial warnings and contraindications that are highly relevant to potential interactions, including those with grapefruit. These include: "The inclusion of 'concomitant use with strong CYP3A4 inhibitors' as a contraindication serves as an implicit warning against grapefruit. Grapefruit is widely recognized in pharmacological literature as a potent inhibitor of CYP3A4. Therefore, while not explicitly named, the leaflet's directive against strong CYP3A4 inhibitors encompasses the interaction with grapefruit. This approach suggests that the manufacturer may assume a certain level of pharmacological knowledge among prescribing healthcare professionals. However, for patients, this implicit warning may not be apparent, highlighting a potential gap between professional prescribing information and patient-facing materials."

Alarm bells here. The leaflet, if telling me nothing else about Inspra (eplerenon) should clearly say AVOID GRAPEFRUIT! I look for whom I should contact. Inspra is branded as an Upjohn product. The leaflet says I should contact Mylan Healthcare Sp. z o.o., and gives a Warsaw telephone number. I am put through to Viatris Trade (ul. Postępu, Warsaw). I get through to an automated message, which tells me to press '3' for enquiries about adverse medical effects. I do so. An American woman's voice informs me "I'm sorry, but the number you dialed has not been recognised." 

Son I phone the regulator, the snappily named Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych**, and get through to an intelligent human to blow the whistle on the bastards. Not only is there no information on the leaflet about avoiding grapefruit, but there's no direct contact with the pharmacovigilance department of the responsible entity for Poland; the leaflet needs to be reprinted with immediate effect.

AI can really useful. No bullshit, no making stuff up, no hallucinations in this case – just the science, with references and notes. 

Moral of the story: this blog post is a matter of record – should I go on to suffer any adverse side-effect resulting from seven weeks of taking Inspra 25mg while consuming 100-150g of grapefruit daily, the world will know why. And I know against whom I should take legal action.

* Bergamot oil is used to flavour Earl Grey tea. Something else I must avoid.

** URPLWMiPB, or Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

This time last year:
Sixty-Six and Two-Thirds

This two years ago:
Marching for Openness and Normality


This time five years ago:
Moonrise, Nowa Wola

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