We asked the hospital pharmacy helpline about Ibrutinib and food / drug interactions. They weren’t sure so asked a clinical pharmacist to email us. We were amazed at how detailed and helpful his response was so share it here as authoritative advice.
Ibrutinib and grapefruit
The interaction between grapefruit juice and ibrutinib is well documented and it is recommended that taking these two at the same time be avoided. Grapefruit juice contains chemicals which inhibit the cytochrome p450 enzyme which is used to breakdown ibrutinib. If this is inhibited, there is a risk of ibrutinib building up in the body and a higher risk of side effects and toxicity developing.[1]
Ibrutinib and seville oranges limes and pomelos
Seville orange juice, also known as bitter orange juice, have also been researched as cytochrome p450 inhibitors, and although the evidence is not as strong, these are also not recommended in the summary of product characteristics.[2] Limes and pomelos seem also to be associated with this blocking cytochrome P450 and should also be avoided.[3]
Ibrutinib and marmelade
Marmalade is traditionally made using bitter oranges. Unfortunately, I have unable to find any evidence that the cooking process will reduce the potential of drug-food interactions and no evidence directly looking at marmalade interacting with ibrutinib or any other medication. Therefore, we would not recommend eating bitter orange marmalade whilst taking ibrutinib, although the comparatively smaller amounts of orange peel and pulp in the marmalade compared to the juice may mean that the risk of toxicity or adverse effects is smaller.
Ibrutinib and sweet orange juice and candied peel
Sweet orange juice (e.g. Naval or Valencia orange juice) does not contain furanocoumarins (the constituent in bitter oranges which appear to inhibit cytochrome p450) and is likely to be safe to drink whilst taking ibrutinib.[3] The research into this, however, looked at the use of orange juice rather than whole oranges or orange rind/peel and so, in the absence of evidence, we would recommend avoiding candied peels.
Ibrutinib and high fat meals
Seville oranges and grapefruit are the only drug-food interactions which are commented upon in the summary of product characteristics. However, there is evidence that ibrutinib taken with a high-fat, high calorie meal (around 50% fat and 800 – 1000kcal) increased the amount of drug getting into the body by 2 fold and increased the maximum level of drug in the body by 2 to 4 fold. The manufacturers recommend that ibrutinib is taken with a meal and a large glass of water, however, they do not make recommendations of the composition of the meal.[1]
Ibrutininb and loperamide or metoclopramide
Ibrutinib taken with loperamide may interact to increase the QT interval which can lead to torsade de pointes and ventricular fibrillation. It is unclear whether this is caused by increased levels of loperamide or that ibrutinib may also increase the QT interval. The British National Formulary (BNF) advises separating the doses of ibrutinib and loperamide by a minimum of 6 hours.
Nytol® (diphenhydramine) and co-codamol both have sedative effects, so care should be taken after taking these medications to avoid driving or using heavy machinery. No interactions between ibrutinib and metoclopramide were found in the literature.[1,4]
1. Baxter K, Preston CL (eds), Stockley’s Drug interactions. [online] London: Pharmacaeutical Press. Available from: www.medicinescomplete.com
2. Janssen-Cilag Ltd. Imbruvica film coated tablets (ibrutinib) Summary of product characteristics. Updated 14.2.2022. Available from: www.medicines.org.uk
3. Bailey DG, Dresser G, Arnold JM. Grapefruit-medication interactions: forbidden fruit or avoidable consequences?. CMAJ. 2013;185(4):309-316. doi:10.1503/cmaj.120951
4. Joint Formulary Committee. British National Formulary (online). London. BMJ Group and Pharmaceutical Press. Available from: www.medicinescomplete.com
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