Oncology, Hematology & Immunology

Form covalent cross-links with DNA (commonly at N7 of guanine), causing strand breaks and inhibition of replication/transcription; cell-cycle nonspecific.

The metabolite acrolein causes hemorrhagic cystitis; prevent with aggressive hydration and mesna, which binds acrolein in the bladder.

Encephalopathy (confusion, somnolence) from the metabolite chloroacetaldehyde; methylene blue may be used for treatment/prophylaxis.

Nephrotoxicity (require aggressive hydration ± mannitol), ototoxicity, peripheral neuropathy, and severe emesis (highly emetogenic). Hypomagnesemia is common.

Dosed by the Calvert equation using AUC and renal function (GFR); dose-limiting toxicity is myelosuppression (thrombocytopenia), with less nephro/neuro/ototoxicity than cisplatin.