Sorafenib

Tyrosine kinase inhibitors

MECHANISM OF ACTION

VEGF receptor TKI: Small molecule tyrosine kinase receptor Inhibits intracellular Raf Kinases and VEGFR, leading to decreased angiogenesis.

MECHANISM OF KIDNEY INJURY

AIN (Acute interstitial nephritis)

CLINICAL KIDNEY SYNDROME

AKI, Proteinuria/Albuminuria, Nephrotic syndrome, Hypertension, Cardiac arrhythmia, QT prolongation.
Extra-renal, rash, impaired wound healing

CARDIOVASCULAR ADVERSE EFFECTS

LYTE ABNORMALITIES

Hypocalcemia, Hypophosphatemia, Hypoalbuminemia, Possible vit D malabsorption

RISK FACTORS

MITIGATION STRATEGIES

Unclear, may need to consider avoiding other offending agents (PPI)

SUGGESTIONS

Discontinue offending drug, Check UA with urine culture, Check urine analysis for cyrstals, WBC, RBC, etc, Monitor renal function panel, ionized Ca, phos, and Vit D levels. In the case report of AIN, patient was treated with prednisone with improvement in Cr.

NOTES/COMMENTS

eGFR 30-59 ml/min, 400 mg BID
eGFR < 30 ml/min, 200 mg Qd

PHARMACOKINETICS

Molecular Weight

464.825 g/mol

Volume of Distribution

213 L

Plasma Protein Binding

99%

Metabolism

Hepatic, via CYP3A4 (primarily oxidated to the pyridine N-oxide; active, minor) and UGT1A9 (glucuronidation)

Bioavailability

38% to 49%; reduced by 29% when administered with a high fat meal

Half-life elimination

25 to 48 hours

Time to peak

3 hours

Excretion

Feces (77%, 51% of dose as unchanged drug); urine (19%, as metabolites)

Dialyzable?

Conflicting. Kennoki et al: not dialyzed (See reference below). 200 mg Qd

REF:

PMID: 17470456
PMID: 22056851
PMID: 19937413
https://www.lumc.nl/sub/4010/att/1683422/1896506

PATHOLOGY SLIDES:

ENTRY UPDATES:

Raad Chowdhury

United States

Sep 25, 2022

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