PARTNERS WITH
Abemaciclib (Verzenio)
CDK4/6 inhibitors
MECHANISM OF ACTION
Abemaciclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor that block the phosphorylation of the retinoblastoma (Rb) protein thus preventing the progression of the cell cycle and arresting tumor growth.
Abemaciclib undergoes hepatic metabolism.
MECHANISM OF KIDNEY INJURY
ATN (Acute tubular necrosis), ATIN (Acute tubulointerstitial nephritis), Water/electrolyte disturbances, Increase in serum creatinine which is likely caused by inhibition of tubular creatinine secretion, increase incidence of urinary tract infections
CLINICAL KIDNEY SYNDROME
AKI, Pseudo AKI (false elevation in Cr), Signs and symptoms related to electrolyte disturbances
CARDIOVASCULAR ADVERSE EFFECTS
Increase risk of VTE
LYTE ABNORMALITIES
Hypomagnesemia, Hypokalemia, Hyperkalemia, Hypocalcemia, Metabolic acidosis (HAGMA, NAGMA), Hypophosphatemia, Hyponatremia, Hypercalcemia, Increase creatinine
RISK FACTORS
MITIGATION STRATEGIES
Ensure follow up of serum creatinine and electrolytes.
SUGGESTIONS
If there is concern for kidney injury, some suggests to use other methods of renal function assessment than serum creatinine to validate the reduction in glomerular filtration rate.
NOTES/COMMENTS
PHARMACOKINETICS
Molecular Weight
Volume of Distribution
Plasma Protein Binding
Metabolism
Bioavailability
Half-life elimination
Time to peak
Excretion
Dialyzable?
Unknown
REF:
- Gupta S, Caza T, Herrmann SM, Sakhiya VC, Jhaveri KD. Clinicopathologic Features of Acute Kidney Injury Associated With CDK4/6 Inhibitors. Kidney Int Rep. Mar 2022;7(3):618-623. doi:10.1016/j.ekir.2021.11.033
- Verzenio (abemaciclib) [product monograph]. Toronto, Ontario, Canada: Eli Lilly Canada Inc; January 2022.
- Company ELa. Verzenio (abemaciclib). U.S. Food and Drug Administration website. Accessed July 19, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208716s006s007s008lbl.pdf.
PATHOLOGY SLIDES:
ENTRY UPDATES:
Anna-Ève Turcotte
United States, Texas
Sep 25, 2022