seville oranges - Marmalade

[RobertCLL]

When on Ibrutinib we know that we should avoid seville oranges. I have had marmalade on toast for my breakfast for as long as I can remember. (Since being on Ibrutinib I have had to make my own marmalade).

My question is, is one spoon of marmalade really going to have an adverse affect?

Any thoughts?

[AussieNeil Administrator]

I would expect that would be a difficult question to answer, given variations in the amount of the CYP450 3A4 enzyme inhibitor in different marmalades, so let's look at why the warning, which comes from the imbruvica.com/ site. Then decide if you want to risk worsening side effects.

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.

drugs.com/food-interactions... in the food interactions rather more scarily states;

Do not consume grapefruit, grapefruit juice, or Seville oranges unless directed otherwise by your doctor. Grapefruit and Seville oranges may significantly increase the blood levels of ibrutinib. This may increase the risk of side effects such as nausea, vomiting, diarrhea, abdominal pain, constipation, hemorrhage, kidney problems, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. You should contact your doctor if you develop paleness, fatigue, dizziness, fainting, unusual bruising or bleeding, fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. Also seek immediate medical attention if you experience signs and symptoms that may suggest kidney damage such as nausea, vomiting, loss of appetite, increased or decreased urination, sudden weight gain or weight loss, fluid retention, swelling, shortness of breath, muscle cramps, tiredness, weakness, dizziness, confusion, and irregular heart rhythm. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

The reason is also given in drugs.com professional interaction data section, where the interaction is noted as Major. (In comparison, the risk of hypertension developing with ibrutinib is noted as Moderate.)

GENERALLY AVOID: Coadministration with grapefruit, grapefruit juice, or Seville oranges may significantly increase the plasma concentrations of ibrutinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Pharmacokinetic modeling suggests that other moderate CYP450 3A4 inhibitors such as diltiazem and erythromycin may increase ibrutinib systemic exposure (AUC) by 6- to 9-fold under fasting condition. The safety and efficacy of these exposures are unknown. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 to 1400 mg) given for 28 days, which yielded single dose AUC values that were approximately 50% greater than steady-state exposures seen at the highest indicated dose of 560 mg.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ibrutinib. The mechanism of interaction is unknown. According to the product labeling, administration with food increases ibrutinib exposure approximately 2-fold compared to administration after overnight fasting.

MANAGEMENT: Patients treated with ibrutinib should avoid consumption of Seville oranges, grapefruit, grapefruit juice, and any supplement containing grapefruit extract.

Neil

[Dawson21 in reply to AussieNeil]

Today I take my "last" 4 Venetoclax tablets (until I might need to restart). How long should I wait before resuming marmalade on toast ? The PIL suggests that Seville oranges risk increasing the levels of V in the blood, so if I've stopped can I resume tomorrow? I really miss my marmalade on toast!

[AussieNeil Administrator in reply to Dawson21]

Sorry, I missed your reply yesterday, so if you haven't already succumbed to that long awaited mouthful, you can probably enjoy your marmalade today. Your risk of side effects reduces dramatically (exponentially) after your last dose.

[Dawson21 in reply to AussieNeil]

Thanks - I resisted the temptation - 2 slices now!

[mrsjsmith]

Robert I was very upset to have to stop Seville marmalade and eating a pink grapefruit, but after spending hours reading labels I have managed to track down blood orange marmalade, ones made without Seville, lemon and lime and rare but bergamot marmalade is delicious. I personally was just too nervous to eat even just that spoonful on my toast.

Colette

[RobertCLL in reply to mrsjsmith]

Colette. Could I ask what brand you went with?

[mrsjsmith]

The blood orange and lemon and lime are the Single Variety Co. They made Bergamot last year but sadly not this year. Rosebud preserves do a lovely sharp rhubarb jam and Fortnum and Mason also have two marmalades without Seville oranges, and they didn’t bat an eyelid when I asked. I assume because some heart medicines can also be affected. As you can see obsessive research. Most companies are also helpful if you email them.

Good luck

Colette

[Skyshark]

Strange, Venetoclax also lists Starfruit as a proscribed food.