PARTNERS WITH
Oxaliplatin
Platinum based Alkylating agents
MECHANISM OF ACTION
Blocks DNA production forming cross-links in DNA resulting in cell arrest/apoptosis/Excreted in urine
MECHANISM OF KIDNEY INJURY
ATN (Acute tubular necrosis), ATIN (Acute tubulointerstitial nephritis), TMA (thrombotic microangiopathy) (systemic/kidney limited), Water/electrolyte disturbances
CLINICAL KIDNEY SYNDROME
AKI, Proteinuria/Albuminuria, Rhabdomyolysis
CARDIOVASCULAR ADVERSE EFFECTS
third-degree atrioventricular block (case report) -PMID: 35833185 - Coronary artery vasospam (PMID: 21686854, PMID: 21969496)
LYTE ABNORMALITIES
Hypokalemia, Hypomagnesemia, Elevated BUN
RISK FACTORS
Pre existing kidney injury, old age, volume depletion
MITIGATION STRATEGIES
Maintaining euvolemia, correction of electrolytes, avoiding concomitant use of other nephrotoxic agents.
SUGGESTIONS
Hold offending drug and rechallenge after AKI/proteinuria resolves, Volume expansion, Check UA with urine culture, Check urine analysis for cyrstals, WBC, RBC, etc, Check urine protein creatinine ratio, Check TMA work up (send haptoglobin, peripheral smear, LDH), Dose adjustment (details in notes section below)
NOTES/COMMENTS
eGFR 30-59 ml/min, full dose
eGFR < 30 ml/min, reduce dose of 65mg/m2 or if curative can consider full dose.
PHARMACOKINETICS
Molecular Weight
397.2858 g/mol
Volume of Distribution
440 L
Plasma Protein Binding
85%
Metabolism
Nonenzymatic (rapid and extensive), forms active and inactive derivatives
Bioavailability
---
Half-life elimination
Half life of 27.3 hours
Terminal half-life of 392 hours
Time to peak
---
Excretion
Urine (54%); 40% in urine in the first 48 hours
Feces (2%)
Dialyzable?
Partially. Oxaliplatin dose of 50% up to normal dose, to be given after HD
REF:
Uptodate
ADDIKD
ACKD part 2
https://pubmed.ncbi.nlm.nih.gov/24615628/#:~:text=Conclusions%3A%20Oxaliplatin%20can%20induce%20various,injury%20secondary%20to%2
PATHOLOGY SLIDES:
ENTRY UPDATES:
Tanazul Pariswala
United States
Sep 25, 2022