should be administered with caution in patients with severe renal
impairment, with close monitoring for signs of toxicity.1
dose adjustments are necessary in patients with mild or moderate
renal impairment. There are no data regarding abemaciclib
administration in patients with severe renal impairment, end stage
renal disease, or in patients on dialysis.1
PopPK analysis mild and moderate renal impairment had no effect on
the exposure of abemaciclib.2
PopPK analysis evaluated 989 individuals including
individuals with mild renal impairment (60 mL/min ≤ CrCL <90
individuals with moderate renal impairment (30 mL/min ≤ CrCL <60
clearance of abemaciclib and its metabolites is minor. Mild and
moderate renal impairment had no effect on the exposure of
abemaciclib. There are no data in patients with severe renal
impairment, end stage renal disease or in patients on dialysis.1
metabolism is the main route of clearance for abemaciclib.
Abemaciclib is metabolised to several metabolites primarily by
cytochrome P450 (CYP) 3A4. The primary biotransformation is
hydroxylation to a metabolite that circulates with an AUC that is 77%
of parent drug. In addition, N-desethyl and N-desethylhydroxy
metabolites circulate at AUCs that are 39% and 15% of parent drug.
These circulating metabolites are active with similar potency to
geometric mean hepatic clearance (CL) of abemaciclib was 21.8 L/h
(39.8% CV), and the mean plasma elimination half-life for abemaciclib
in patients was 24.8 hours (52.1% CV). After a single oral dose
‑abemaciclib, approximately 81% of the dose was excreted in
faeces and 3.4% excreted in urine. The majority of the dose
eliminated in faeces was metabolites.1
on Serum Creatinine
not an adverse reaction, abemaciclib has been shown to increase serum
of patients (based on laboratory findings),
Grade 3 or 4 (based on laboratory findings).1
has been shown to increase serum creatinine due to inhibition of
renal tubular secretion transporters without affecting glomerular
function (as measured by iohexol clearance).1
the MONARCH 2 and MONARCH 3 trials, increased serum creatinine was
the most common laboratory abnormality reported with 97% and 96% of
patients, respectively, having a grade 1 or 2 event.3,4
healthy subjects, mean maximum creatinine increases of approximately
20% to 35% over baseline values occurred at about 24 hours postdose
and then returned to baseline at about 336 hours (14 days) postdose.2
clinical studies, increases in serum creatinine occurred
the first month of abemaciclib dosing,
elevated but stable through the treatment period,
reversible upon treatment discontinuation,
were not accompanied by changes in markers of renal function, such as
blood urea nitrogen (BUN), cystatin C, or calculated glomerular
filtration rate based on cystatin C.1
measures of renal function (such as cystatin C) should be used as an
alternative to either serum creatinine or creatinine-based calculated
estimates of GFR if
creatinine rise is progressive after the first cycle
are other indications of renal injury (eg, proteinuria, etc.), or
patient has a need for precise GFR assessment (such as concomitant
medications that effect kidney function).5,6
may not be an accurate method to assess renal function in these
C is a small protein that is produced by all nucleated cells and
found in body fluids, including serum. It is formed at a constant
rate and due to its small size is freely filtered by the glomeruli.
Cystatin C is not secreted and is fully reabsorbed and broken down by
the renal tubules.7
Cystatin C has been consistently found to have a higher correlation
with standard measures of GFR when compared with creatinine.8
or plasma cystatin C measurement is an automated test that is readily
available and does not require special processing or handling of the
Verzenios [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in
combination with fulvestrant in women with HR+/HER2- advanced breast
cancer who had progressed while receiving endocrine therapy. J
Clin Oncol. 2017;35(25):2875-2884.
Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial
therapy for advanced breast cancer. J Clin Oncol.
Milburn J, Jones R, Levy JB. Renal effects of novel antiretroviral
drugs. Nephrol Dial Transplant. 2017;32(3):434-439.
Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C
versus creatinine in determining risk based on kidney function. N
Eng J Med. 2013;369(10):932-943.
Chew JSC, Saleem M, Florkowski CM, George PM. Cystatin C – a
paradigm of evidence based laboratory medicine. Clin Biochem Rev.
Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular
filtration rate from serum creatinine and cystatin C. N Engl J
Med. 2012;367(1):20-29. https://doi.org/10.1056/NEJMoa1114248
Shlipak MG, Mattes MD, Peralta CA. Update on cystatin C:
incorporation into clinical practice. Am J Kidney Dis.
= creatinine clearance
= coefficient of variation
= cytochrome P450
= glomerular filtration rate
= population pharmacokinetic
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.