Please use a minimum of three unique search words
Our search is configured to only display links relevant to answer your question. For the best results please use specific and relevant keywords that accurately reflect the information you are seeking.
Please do not use this field to report adverse events or product complaints. Adverse events and product complaints should be reported. Reporting forms and information can be found at UK: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events and product complaints should also be reported to Lilly: please call Lilly UK on 01256 315 000.
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).
Are there any drug to drug interactions with Verzenios® ▼ (abemaciclib)?
Abemaciclib interacts with strong and moderate CYP3A inducers and inhibitors.
Metabolism of Abemaciclib
Hepatic metabolism is the main route of clearance for abemaciclib.1
Abemaciclib is metabolized to several metabolites primarily by cytochrome P450 (CYP) 3A.1
The major metabolism pathway is formation of
- N-desethylabemaciclib (M2).1
Additional metabolites include
- hydroxyabemaciclib (M20)
- hydroxy-N-desethylabemaciclib (M18), and
- an oxidative metabolite (M1).1
Of these metabolites, M2, M18, and M20 are active with similar potency as abemaciclib.1
Effect of Other Drugs on Abemaciclib
Strong CYP3A Inhibitors
Avoid using strong CYP3A4 inhibitors together with abemaciclib.2
Co-administration of abemaciclib with CYP3A4 inhibitors can increase plasma concentrations of abemaciclib. In patients with advanced and/or metastatic cancer, co‑administration of the CYP3A4 inhibitor clarithromycin resulted in a 3.4‑fold increase in the plasma exposure of abemaciclib and a 2.5‑fold increase in the combined unbound potency adjusted plasma exposure of abemaciclib and its active metabolites.2
Examples of strong CYP3A4 inhibitors include, but not limited to: clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, posaconazole or voriconazole. Avoid grapefruit or grapefruit juice. 2
Concomitant use of strong CYP3A4 inhibitors should be avoided. If strong CYP3A4 inhibitors cannot be avoided, the abemaciclib dose should be reduced to 100 mg twice daily.2
In patients who have had their dose reduced to 100 mg abemaciclib twice daily and in whom co-administration of a strong CYP3A4 inhibitor cannot be avoided, the abemaciclib dose should be further reduced to 50 mg twice daily.2
In patients who have had their dose reduced to 50 mg abemaciclib twice daily and in whom co‑administration of a strong CYP3A4 inhibitor cannot be avoided, the abemaciclib dose may be continued with close monitoring of signs of toxicity. 2
If the CYP3A4 inhibitor is discontinued, the abemaciclib dose should be increased to the dose used prior to the initiation of the CYP3A4 inhibitor (after 3 to 5 half-lives of the CYP3A4 inhibitor).2
Topical ketoconazole is not expected to interact with abemaciclib due to minimal systemic absorption of topical products.3
Avoid grapefruit or grapefruit products.1
Moderate CYP3A Inhibitors
No dose adjustment is necessary for patients treated with moderate or weak CYP3A4 inhibitors. There should, however, be close monitoring for signs of toxicity.2
Strong and moderate CYP3A Inducers
Co-administration of abemaciclib with the strong CYP3A4 inducer rifampicin decreased the plasma concentration of abemaciclib by 95% and unbound potency adjusted plasma concentration of abemaciclib plus its active metabolites by 77% based on AUC0-∞. 2
Concomitant use of strong CYP3A4 inducers (including, but not limited to: carbamazepine, phenytoin, rifampicin and St. John’s wort) should be avoided due to the risk of decreased efficacy of abemaciclib.2
Coadministration of a single 8 mg dose of loperamide with a single 400 mg dose of abemaciclib in healthy subjects increased the relative potency adjusted unbound AUC0-INF of abemaciclib plus its active metabolites by 12%, which is not considered clinically relevant.1
In clinical studies in patients with breast cancer, there was no clinically relevant effect of fulvestrant, anastrozole, letrozole, or exemestane on the PK of abemaciclib.1
Based on the solubility and metal ion binding characteristics of abemaciclib, acid-reducing agents are not expected to affect the oral absorption of abemaciclib.1
A clinical study to evaluate the impact of acid-reducing agents, such as histamine H2-receptor antagonists (H2) blockers and proton pump inhibitors, on abemaciclib absorption has not been conducted. However, because abemaciclib 200 mg is soluble in solutions up to potential of hydrogen (pH) 6.8, coadministration of acid-reducing agents is unlikely to have an effect on the absorption and exposure of abemaciclib.1
An in vitro study was conducted to evaluate the risk of an interaction between abemaciclib and metal ions (magnesium, calcium, iron, bismuth, zinc, and aluminum) commonly found in antacids. Abemaciclib did not interact with any of the metal ions that are commonly found in antacids.1
Effect of Abemaciclib on Other Agents
In a clinical drug interaction study in healthy subjects, coadministration of a single 8 mg dose of loperamide with a single 400 mg dose of abemaciclib in healthy subjects (2.7 times the approved recommended 150 mg dosage) increased the relative potency AUC0-INF of abemaciclib plus its active metabolites by 12%, and increased loperamide AUC0-INF by 9% and maximum concentration (Cmax) by 35% relative to loperamide alone. These effects are not considered clinically relevant.1
In a clinical drug interaction study in healthy subjects, coadministration of a single 1000 mg dose of metformin, a clinically relevant substrate of renal OCT2, and MATE1 and 2-K transporters, with a single 400 mg dose of abemaciclib (2.7 times the approved recommended 150 mg dosage) increased metformin AUC0-INF by 37% and Cmax by 22% relative to metformin alone. Abemaciclib reduced the renal clearance and renal secretion of metformin by 45% and 62%, respectively, relative to metformin alone, without any effect on glomerular filtration rate as measured by iohexol clearance and serum cystatin C.1
In a clinical study in patients with breast cancer, there was no clinically‑relevant pharmacokinetic drug interaction between abemaciclib and anastrozole, fulvestrant, exemestane, letrozole or tamoxifen.2
It is currently unknown whether abemaciclib may reduce the effectiveness of systemically acting hormonal contraceptives, and therefore women using systemically acting hormonal contraceptives are advised to add a barrier method.2
CYP Metabolic Pathways
In a phase 1 clinical drug interaction study, patients with advanced and/or metastatic cancer received a drug cocktail containing 4 sensitive CYP substrates alone and in combination with abemaciclib.
The drug cocktail CYP substrates included
- 0.2 mg midazolam (CYP3A4)
- 10 mg S-warfarin (CYP2C9)
- 30 mg dextromethorphan (CYP2D6), and
- 100 mg caffeine (CYP1A2).4
The following PK results were observed.
- Midazolam AUC0-inf was approximately 13% lower and the Cmax was approximately 15% lower when midazolam was administered in combination with abemaciclib versus when midazolam was administered alone,
- no significant differences in PK between S-warfarin and dextromethorphan when administered in combination with abemaciclib, and
- AUC0-inf of caffeine was 56% higher when caffeine was administered in combination with abemaciclib compared to administration alone.4
Non-compliance with caffeine restriction was evident in the data before and after drug cocktail administration, but given the patient variability for caffeine AUC, the effect observed for caffeine AUC0-INF is not considered clinically relevant.4
In Vitro Transporter Studies
Abemaciclib and its major active metabolites inhibit the renal transporters OCT2, MATE1, and MATE2-K at concentrations achievable at the approved recommended dosage. The observed serum creatinine increase in clinical studies with abemaciclib is likely due to inhibition of tubular secretion of creatinine via OCT2, MATE1, and MATE2-K. Abemaciclib and its major metabolites at clinically relevant concentrations do not inhibit the hepatic uptake transporters OCT1, organic anion transporter (OAT) P1B1, and OATP1B3, or the renal uptake transporters OAT1 and OAT3.1
In an in vitro study, abemaciclib and its major active metabolites downregulated the messenger RNA (mRNA) of various CYP isoforms (1A2, 2B6, 2C8, 2C9, 2D6, 3A4, and 3A5) and decreased the catalytic activities of CYP1A2, CYP2B6, and CYP3A4 enzymes. The results did not translate into clinically meaningful drug-drug interactions. The lack of clinically meaningful drug-drug interactions suggest further studies are needed to understand the downregulation of CYP isoforms in vitro.4
Abemaciclib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Abemaciclib and its major active metabolites are not substrates of hepatic uptake transporters OCT1, OATP1B1, or OATP1B3.1
Abemaciclib inhibits P-gp and BCRP. The clinical consequences of this finding on sensitive P-gp and BCRP substrates are unknown.1
1Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2Verzenios [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
3Lexicomp Online™ Lexi-Drugs: Ketoconazole (topical). In: Lexi-Drugs, Lexicomp Online. Hudson, OH: Lexi-Comp, Inc. Available at: http://online.lexi.com. Updated January 20, 2022. Accessed January 20, 2022.
4Turner PK, Hall SD, Chapman SC, et al. Abemaciclib does not have a clinically meaningful effect on pharmacokinetics of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 substrates in patients with cancer. Drug Metab Dispos. 2020;48(9):796-803. https://doi.org/10.1124/dmd.119.090092
▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
Date of Last Review: 19 January 2022