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Verzenios ® ▼ (abemaciclib)
This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. For current prescribing information for all Lilly products, including Summaries of Product Characteristics, Patient Information Leaflets and Instructions for Use, please visit: www.medicines.org.uk (England, Scotland, Wales) or www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).
Should other citrus fruits be avoided with Verzenios® (abemaciclib) apart from grapefruit?
Furanocoumarins in grapefruit and its juice inhibit CYP34A, the enzyme metabolising abemaciclib. Seville oranges, limes and pomelos can also contain high levels of furanocoumarins, while sweet oranges contain little or no levels.
Verzenios is a substrate of CYP3A4
Abemaciclib is primarily metabolised by CYP3A4.1
Use of strong CYP3A4 inhibitors together with abemaciclib should be avoided. If strong CYP3A4 inhibitors need to be co-administered, the dose of abemaciclib should be reduced, followed by careful monitoring of toxicity.1
Examples of strong CYP3A4 inhibitors include, but are not limited to: clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, posaconazole or voriconazole. Avoid grapefruit or grapefruit juice. 1
Although the pharmacokinetic interactions of abemaciclib with citrus fruits have not been systematically evaluated, the following data about interactions of CYP3A4 substrates with citrus fruits may inform your clinical decision.
Grapefruit and its juice inhibits CYP3A4
Grapefruit and its juice contain furanocoumarins, such as bergamottin, epoxybergamottin, and 6′,7′-dihydroxybergamottin that inhibit the CYP3A4 enzyme.2
One whole grapefruit or 200 mL of grapefruit juice is sufficient to cause clinically relevant increased systemic drug concentration and subsequent adverse effects.3
Seville oranges, limes and pomelos also contain furanocoumarins
Other citrus fruits like Seville oranges, pomelos and limes contain relatively high levels of furanocoumarins.6-8
Are sweet oranges and mandarins safe to eat?
Sweet oranges, mandarins and mandarin hybrids contains little or no furanocoumarins and will not affect the activity of CYP3A4.9
It is essential to know that many citrus fruits, including oranges, are cross-bred and can contain furanocoumarins and therefore impact CYP3A4.
1Verzenios [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Hung WL, Suh JH, Wang Y. Chemistry and health effects of furanocoumarins in grapefruit. J Food Drug Anal. 2017;25(1):71-83. doi:10.1016/j.jfda.2016.11.008.
3Bailey DG, Dresser G, Arnold JM. Grapefruit-medication interactions: forbidden fruit or avoidable consequences?. CMAJ. 2013;185(4):309-316. doi:10.1503/cmaj.120951.
4Edgar B, Bailey D, Bergstrand R, Johnsson G, Regårdh CG. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance. Eur J Clin Pharmacol. 1992;42(3):313-317. doi:10.1007/BF00266354.
5Bailey DG, Dresser GK, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit-felodipine interaction: effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther. 2000;68(5):468-477. doi:10.1067/mcp.2000.110774.
6Malhotra S, Bailey DG, Paine MF, Watkins PB. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin Pharmacol Ther. 2001;69(1):14-23. doi:10.1067/mcp.2001.113185.
7Guo LQ, Chen QY, Wang X, et al. Different roles of pummelo furanocoumarin and cytochrome P450 3A5*3 polymorphism in the fate and action of felodipine. Curr Drug Metab. 2007;8(6):623-630. doi:10.2174/138920007781368917.
8Masuda M, Watanabe S, Tanaka M, Tanaka A, Araki H. Screening of furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in citrus. J Clin Pharm Ther. 2018;43(1):15-20. doi:10.1111/jcpt.12595.
9Dugrand-Judek A, Olry A, Hehn A, et al. The Distribution of Coumarins and Furanocoumarins in Citrus Species Closely Matches Citrus Phylogeny and Reflects the Organization of Biosynthetic Pathways. PLoS One. 2015;10(11):e0142757. Published 2015 Nov 11. doi:10.1371/journal.pone.0142757.
Date of Last Review: 06 October 2023