PARTNERS WITH
Ifosfamide
Non-platinum based Alkylating Agents
MECHANISM OF ACTION
Ifosfamide causes cross-linking of strands of DNA by binding with nucleic acids and other intracellular structures, resulting in cell death; inhibits protein synthesis and DNA synthesis
Excretion : Urine
MECHANISM OF KIDNEY INJURY
AIN (Acute interstitial nephritis), ATN (Acute tubular necrosis), Fanconi syndrome , and nephrogenic DI
CLINICAL KIDNEY SYNDROME
myelosuppression, IPF, pneumonitis, hemorrhagic cystitis (acrolein), anovulation, gonadal failure, menopause, bladder cancer, teratogenic, AML Neurotoxicity-seizure
CARDIOVASCULAR ADVERSE EFFECTS
LYTE ABNORMALITIES
Hypokalemia, Hyporeninemia, Hypocalcemia, Metabolic acidosis (HAGMA, NAGMA), SIADH , renal rickets
RISK FACTORS
Dose reduction with renal impairment.
MITIGATION STRATEGIES
To prevent bladder toxicity, ifosfamide should be given with mesna and hydration (at least 2 L of oral or IV fluid per day). Dose reduction in patients with kidney impairment
SUGGESTIONS
Check urine analysis for cyrstals, WBC, RBC, etc, Check urine protein creatinine ratio.
Dose adjustment
-CrCl 46 to 60 mL/minute: Administer 80% of dose CrCl 31 to 45 mL/minute: Administer 75% of dose CrCl <30 mL/minute: Administer 70% of dose.
-Krens (2019); Avoid if eGFR< 60 ml/min
NOTES/COMMENTS
PHARMACOKINETICS
Molecular Weight
261
Volume of Distribution
Plasma Protein Binding
negligible
Metabolism
microsomal hyrodxylation
Bioavailability
Half-life elimination
High Dose 15 hours, Low Dose 7 hours
Time to peak
Excretion
Renal, High dose 70-86% Lower dose 12-18%
Dialyzable?
use is not recommended
REF:
Ifosfamide [prescribing information]. Parsippany, NJ: Teva Pharmaceuticals USA, Inc; February 2020.
PATHOLOGY SLIDES:
ENTRY UPDATES:
Kartik Kalra
United States
Sep 25, 2022