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Verzenios ® (abemaciclib)
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How to manage hepatic toxicities in Verzenios® (abemaciclib) treated patients
Dose interruption, reduction, discontinuation, or delay in starting treatment cycles is recommended for persistent or recurrent grade 2, 3 or 4, hepatic transaminase elevations. Please find detailed information below.
Management Recommendations for Hepatic Toxicities
Monitor alanine aminotransferase (ALT) and aspartate aminostransferase (AST)
- prior to the start of abemaciclib therapy
- every two weeks for the first two months
- monthly for the next two months, and
- as clinically indicated.1
Please find management recommendations for increased aminotransferases in Management recommendations for increased aminotransferases.
Toxicitya |
Management recommendations |
Grade 1 (>ULN-3.0 x ULN) Grade 2 (>3.0-5.0 x ULN) |
No dose adjustment required. |
Persistent or Recurrent Grade 2, or Grade 3 (>5.0-20.0 x ULN) |
Suspend dose until toxicity resolves to baseline or Grade 1. Resume at next lower dose. |
Elevation in AST and/or ALT >3 x ULN WITH total bilirubin >2 x ULN, in the absence of cholestasis |
Discontinue abemaciclib. |
Grade 4 (>20.0 x ULN) |
Discontinue abemaciclib. |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal
aNCI CTCAE
In the metastatic breast cancer trials, the increases in hepatic transaminases were manageable by dose reduction or suspension and resolved after discontinuing abemaciclib.2
Incidence and Duration of Hepatic Toxicities in Clinical
For ALT
- the median time to onset of Grade 3 or 4 ALT elevation was 57 to 61 days, and
- following management recommendations the median time to resolution was 14 days.
For AST
- the median time to onset of Grade 3 or 4 AST elevation was 71 to 185 days, and
- the median time to resolution was 13 to 15 days.1
Please find ALT, AST and blood bilirubin increases in MONARCH 2 and MONARCH 3 in ALT and AST Increases in MONARCH 2 and MONARCH 3, Blood Bilirubin Increased in MONARCH 2 andBlood Bilirubin Increased in MONARCH 3.
Abemaciclib + NSAI |
Placebo + NSAI |
Abemaciclib + Fulvestrant |
Placebo + Fulvestrant |
|
Event |
MONARCH 3 |
MONARCH 2 |
||
Grade ≥3 ALT increase |
6% |
2% |
4% |
2% |
Median time to onset |
64 days |
--- |
57 days |
--- |
Median time to resolutiona |
14 days |
--- |
14 days |
--- |
Grade ≥3 AST increase |
4% |
1% |
2% |
3% |
Median time to onset |
87 days |
--- |
185 days |
--- |
Median time to resolutiona |
15 days |
--- |
13 days |
--- |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; NSAI = nonsteroidal aromatase inhibitor.
aTo normalization or grade <3.
CTCAE, % |
All Grades |
Grade 1 |
Grade 2 |
Grade 3 |
Grade 4 |
Grade 5 |
Abemaciclib + Fulvestrant, N=441 |
||||||
Blood bilirubin increased |
1.6 |
0 |
0.7 |
0.9 |
0 |
0 |
|
Placebo + Fulvestrant, N=223 |
|||||
Blood bilirubin increased |
0.9 |
0.4 |
0.4 |
0 |
0 |
0 |
Abbreviation: CTCAE = Common Terminology Criteria for Adverse Events.
CTCAE, % |
All Grades |
Grade 1 |
Grade 2 |
Grade 3 |
Grade 4 |
Grade 5 |
|
Abemaciclib + NSAI, N=327 |
|||||
Blood bilirubin increased |
1.8 |
0.6 |
0.3 |
0.9 |
0 |
0 |
|
Placebo + NSAI, N=161 |
|||||
Blood bilirubin increased |
0.6 |
0.6 |
0 |
0 |
0 |
0 |
Abbreviations: CTCAE = Common Terminology Criteria for Adverse Events; NSAI = nonsteroidal aromatase inhibitor.
References
1Verzenios [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
2Data on file, Eli Lilly and Company and/or one of its subsidiaries.
3Rugo HS, Huober J, Garcia-Saenz JA, et al. Management of abemaciclib-associated adverse events in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: safety analysis of MONARCH 2 and MONARCH 3. Oncologist. 2021;26(1):e53-e65. http://dx.doi.org/10.1002/onco.13531
Date of Last Review: 19 January 2022