Palbociclib (Ibrance)

CDK4/6 inhibitors

MECHANISM OF ACTION

Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor that blocks the phosphorylation of the retinoblastoma (Rb) protein thus preventing the progression of the cell cycle and arresting tumor growth.
Palbociclib undergoes hepatic metabolism.

MECHANISM OF KIDNEY INJURY

ATN (Acute tubular necrosis), ATIN (Acute tubulointerstitial nephritis), Water/electrolyte disturbances, Increase in serum creatinine which may be related to 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

QT interval prolongation --PMID: 31529317. ---- atrial fibrillation , myocardial infarction, cardiac failure (from abstract looking into FAERS) -https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.e13038 and https://www.ahajournals.org/doi/10.1161/JAHA.123.029361

LYTE ABNORMALITIES

Hypercalcemia, Hypocalcemia, Hyponatremia, Hypophosphatemia, Hypomagnesemia, Hypernatremia, Hyperkalemia, Hypokalemia, 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
- Ibrance (palbociclib) [product monograph]. Kirkland, Quebec, Canada: Pfizer Canada ULC; July 2021.
- Pfizer. Ibrance (palbociclib). U.S. Food and Drug Administration website. Accessed July 19, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/207103s008lbl.pdf.

PATHOLOGY SLIDES:

ENTRY UPDATES:

Anna-Ève Turcotte

United States, Texas

Sep 25, 2022

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