Venetoclax and Seville oranges : Apologies if... - CLL Support

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Venetoclax and Seville oranges

Fowey2009 profile image
16 Replies

Apologies if this has been asked before, but I am just thinking about making a Christmas cake.

I know people on venetoclax can’t eat Seville oranges or marmalade made with them. Stupid question coming up - does this mean other oranges are ok? (And if so, why only Seville oranges?)

Many thanks

Beryl

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Fowey2009 profile image
Fowey2009
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16 Replies
fapumpkin profile image
fapumpkin

I think other oranges are ok? You also can't eat: grapefruits, star fruit or pomegranates.

The following is taken from cancer research uk:

"CYP enzymes

A group of enzymes called cytochrome P (CYP) are an important part of the process of how drugs are broken down in the body after they’ve been absorbed into the blood. Most of these enzymes are made by the liver.

There are many CYP enzymes. We know that certain ones affect how cancer drugs are broken down in the body. These include:

CYP3A

CYP4A

CYP2A

CYP5A

The amount of these enzymes in the body can affect how well the cancer drug is broken down. This affects how well the drug works and the possible side effects.

If too much of the cancer drug is broken down it might not work as well, and you might need a bigger dose which can possibly cause more side effects. If too little of the drug is broken down, you could have bad side effects from your cancer drug and you might need a smaller dose.

Foods and other drugs, including herbal supplements, can affect the level of CYP enzymes in the body. So while you are taking certain drugs, your healthcare team may tell you to avoid some foods or herbal supplements. You may also read this in the drug information sheet enclosed with your medicine. Check with your doctor or pharmacist if you’re not sure.

Foods that affect CYP enzymes

The best known foods that affect the CYP enzymes are grapefruit and Seville oranges. This includes their juice and other products that are mostly made from these, for example marmalade.

The food and drink you may need to avoid depend on the drug you are having and which CYP enzymes are involved. Your doctor or pharmacist will tell you if you need to avoid particular foods or drink while on treatment."

lankisterguy profile image
lankisterguyVolunteer

Hi Fowey2009 - Beryl-

Yes the restriction only applies to Seville (bitter) oranges, grapefruit, starfruit (and possibly pomegranate) since they contain a chemical that affect how long Venetoclax stays in your body.

-

webmd.com/drugs/2/drug-1715...

-

drugs.com/food-interactions....

-

Other citrus like oranges, lemons, etc. do not contain the problem chemical and will not affect the amount of Venetoclax in your body.

-

Len

DRM18 profile image
DRM18

Hi Beryl,

I fresh-squeeze a glass of lemon water every morning & also cut up a navel orange for breakfast. Been on Venetoclax since March!

—Dave

Michaeljohn50 profile image
Michaeljohn50

Good morning Fowey2009,been on Venetoclax since April. I have temporarily abandoned marmalade but enjoy fresh orange juice most days and periodic oranges, satsumas etc without any issues.

So far, so good.

Michael

Fowey2009 profile image
Fowey2009

Thank you all very much for your advice, which is reassuring. Best wishes. Beryl

Psmithuk profile image
Psmithuk in reply to Fowey2009

I’m wondering if home made lemon and/or sweet orange marmalade would be OK.

AussieNeil profile image
AussieNeilAdministrator in reply to Psmithuk

It's just the seville orange and grapefruit citrus varieties that are of most concern. To minimise any risk, enjoy your marmalade at the opposite end of the day from when you take your Ibrutinib.

Neil

Psmithuk profile image
Psmithuk in reply to AussieNeil

Thanks, Neil. Just preparing myself for possible future eventualities!Cx

Patc890USA profile image
Patc890USA in reply to AussieNeil

Neil, when I started Venetoclax almost 2 years ago I read an article on the NIH site that suggested Clementines could also be a problem. My doctors at NIH suggested I avoid them also. The last sentence or the article stated.

"Our data indicate that clementine juice similar to grapefruit juice bears the potential for profound interactions with drugs potentially leading to adverse drug effects e.g. through over-exposure to CYP3A4 substrates."

Here's the article.

pubmed.ncbi.nlm.nih.gov/278...

Pat.

AussieNeil profile image
AussieNeilAdministrator in reply to Patc890USA

Thanks Pat,

The article you referenced is not specifically about Ibrutinib/Imbruvica interactions, though I agree that the study is relevant, given we are talking about the effect on the CYP34A enzyme as the underlying causative factor. The article states "All citrus juices profoundly induced several drug transporters and drug metabolising enzymes, whereas the effects of grapefruit juice were most pronounced (e.g. 156-fold and 34-fold induction of cytochrome P450 (CYP) 3A4 mRNA by grapefruit juice and clementine juice, respectively". Mandarins also get a mention. This doesn't surprise me, as per the article, I expected that CYP34A inhibition would probably occur to varying degrees with all citrus fruits, which is why I suggested eating marmalade at the opposite end of the day to minimise any risk.

The key concern would be the amount of potential inhibition. Your referenced article notes almost a 5 fold greater induction by grape juice compared to clementine juice. The official Ibrutinib website, imbruvica.com , only states:

"What should I avoid while taking IMBRUVICA®?You should not drink grapefruit juice, eat grapefruit, or eat Seville oranges (often used in marmalades) during treatment with IMBRUVICA®. These products may increase the amount of IMBRUVICA® in your blood."

So certainly anyone on Ibrutinib who enjoys citrus fruits might want to consider either shifting their consumption of clementines and mandarins away from when they take Ibrutinib or perhaps even consider avoiding them and even all citrus fruits if they notice worse side effects when they consume them, but officially it's only grapefruit and seville oranges that we are warned about. I've referenced this post in our pinned post on Imbruvica/Ibrutinib drug interactions: healthunlocked.com/cllsuppo....

Neil

JustAGuy profile image
JustAGuy in reply to AussieNeil

Does this also apply to Venetaclax?

AussieNeil profile image
AussieNeilAdministrator in reply to JustAGuy

Yes, the official advice with respect to Venetoclax/Venclexta, is to avoid grapefruit, seville oranges and starfruit. Specifically "Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS)."

venclextahcp.com/cll/dosing...

mrsjsmith profile image
mrsjsmith in reply to Psmithuk

Yes they are. It’s only the Seville oranges that are the problem. I spent ages looking at the backs of labels to see what oranges are used, but they rarely say. I was pleasantly surprised when I asked in Fortnum and Mason if they had any marmalade not made with Seville oranges and I was shown two different ones. I believe some heart medication is also affected.Sadly lemon is just not the same as bitter Seville marmalade. Rhubarb and ginger jam is a good alternative.

Colette

Psmithuk profile image
Psmithuk in reply to mrsjsmith

All good news - not that I need to know yet, just a passing thought.😀 - just in case!Thanks

Cx

PaulaS profile image
PaulaSVolunteer

Hi Beryl,

When I started Ibrutinib, I stopped all grapefruit and marmalade as instructed.

I continued eating ordinary oranges and things that contained lemon, but soon realised they all gave me stomach upsets and a general "unwell" feeling. So, I now avoid ALL citrus fruits. Even the little bits in mince pies and Christmas cake don't work well for me - though sometimes I eat them regardless because I love them!

My problem may not be entirely the CYP enzyme content, it might be the acid content of citrus, as I've always had a bit of problem with stomach acid.

AussieNeil 's suggestion appeals to me - that of eating the suspect citrus stuff at the opposite time of day to the ibrutinib. I suppose it's a matter of degree - lots of things contain the CYP enzymes, but some have much more than others - with grapefruit being the worst offender.

So, I'll still stay off the grapefruit, Seville oranges and pomegranate, but mince pies and Christmas cake.. Hmmm...

Paula

P.S. Wishing you (and your husband) all the best in your baking for Christmas!

Oleboyredw-uk profile image
Oleboyredw-uk

In the documentation supplied when I started Venetoclax (early 2017) it listed Grapefruit, Seville Oranges, Star Fruit and Pomelos as the four things to avoid.

Marmalade was a favourite so it felt like quite a blow, but I soon adapted. I was told Blood Orange Marmalade was an option. I contacted the maker and their response was “yes it is only blood orange, brought in as pulp from Spain”. That discussion went nowhere and I switched to raspberry conserve on my toast. A small sacrifice in my opinion. I suppose as an alternative I could have made it myself!

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