Verzenios ® (abemaciklib)

För fullständig produktresumé för Verzenios se FASS.

Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska

Verzenios® ▼ (abemaciclib): Användning hos patienter med nedsatt njurfunktion

Ingen dosjustering av Verzenios (abemaciclib) krävs för patienter med lätt eller måttligt nedsatt njurfunktion.

Dose Frequency/Modification

Abemaciclib should be administered with caution in patients with severe renal impairment, with close monitoring for signs of toxicity.1

No 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

In a PopPK analysis mild and moderate renal impairment had no effect on the exposure of abemaciclib.2

The PopPK analysis evaluated 989 individuals including

  • 383 individuals with mild renal impairment (60 mL/min ≤ CrCL <90 mL/min), and

  • 127 individuals with moderate renal impairment (30 mL/min ≤ CrCL <60 mL/min).2

Metabolism and Elimination

Renal 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

Hepatic 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 abemaciclib.1

The 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 of [14C] ‑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

Effect on Serum Creatinine

Although not an adverse reaction, abemaciclib has been shown to increase serum creatinine in

  • 98.3% of patients (based on laboratory findings),

  • 1.9% Grade 3 or 4 (based on laboratory findings).1 

Abemaciclib 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

In 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

In 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

 In clinical studies, increases in serum creatinine occurred

  • within the first month of abemaciclib dosing,

  • remained elevated but stable through the treatment period,

  • were reversible upon treatment discontinuation,

and 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

Other 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

  • serum creatinine rise is progressive after the first cycle

  • there are other indications of renal injury (eg, proteinuria, etc.), or

  • a patient has a need for precise GFR assessment (such as concomitant medications that effect kidney function).5,6

Creatinine may not be an accurate method to assess renal function in these patients.2,5,6

Cystatin 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

Serum or plasma cystatin C measurement is an automated test that is readily available and does not require special processing or handling of the blood sample.9

References

1. Verzenios [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3. 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. http://dx.doi.org/10.1200/JCO.2017.73.7585.

4. Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638-3646. https://doi.org/10.1200/jco.2017.75.6155.

5. Milburn J, Jones R, Levy JB. Renal effects of novel antiretroviral drugs. Nephrol Dial Transplant. 2017;32(3):434-439. https://doi.org/10.1093/ndt/gfw064

6. 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. https://doi.org/10.1056/NEJMoa1214234

7. Chew JSC, Saleem M, Florkowski CM, George PM. Cystatin C – a paradigm of evidence based laboratory medicine. Clin Biochem Rev. 2008;29(2):47-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2533150/

8. 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

9. Shlipak MG, Mattes MD, Peralta CA. Update on cystatin C: incorporation into clinical practice. Am J Kidney Dis. 2013;62(3):595-603. https://doi.org/10.1053/j.ajkd.2013.03.027

Glossary

CG = Cockroft-Gault

CrCL = creatinine clearance

CV = coefficient of variation

CYP = cytochrome P450

GFR = glomerular filtration rate

PopPK = population pharmacokinetic 

t1/2 = half-life

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.

Datum fӧr senaste ӧversyn 2018 M07 30


Kontakta Medicinsk Information på Lilly

Kontakta oss på telefon

Kontorstid vardagar 9.00-17.00

Eller så kan du

Skriv din fråga till oss