See package insert for more detailed information. 18.3 Mesna Source and Pharmacology [(sodium 2- mercaptoethane sulfonate, UCB 3983, Mesnex®) NSC #113891] was developed as a prophylactic agent to reduce the risk of hemorrhagic cystitis induced by ifosfamide. Mesna is rapidly oxidized to its major metabolite, mesna disulfide (dimesna). Mesna disulfide remains in the intravascular compartment and is rapidly eliminated by the kidneys. In the kidney, the mesna disulfide is reduced to the free thiol compound, mesna, which reacts chemically with the urotoxic ifosfamide metabolites (acrolein and 4 -hydroxy -ifosfamide) resulting in their detoxification. The first step in the detoxification process is the binding of mesna to 4 -hydroxy ifosfamide forming a nonurotoxic 4- sulfoethylthioifosfamide. Mesna also binds to the double bonds of acrolein and to other urotoxic metabolites. In multiple human xenograft or rodent tumor model studies, mesna in combination with ifosfamide (at dose ratios of up to 20- fold as single or multiple courses) failed to demonstrate interference with antitumor efficacy. After an 800 mg dose the half -life for Mesna and DiMesna are 0.36 hours and 1.17 hours, respectively. Approximately 32% and 33% of the administered dose was eliminated in the urine in 24 hours as mesna and dimesna, respectively. The majority of the dose recovered was eliminated within 4 hours. Mesna tablets have an oral bioavailability of 45- 79% and a urinary bioavailability which ranged from 45- 79% of intravenously administered mesna. The oral bioavailability is unaffected by food. When compared to intravenously administered mesna, the intravenous plus oral dosing regimen increases systemic exposures (150%) and provides more sustained excretion of mesna in the urine over a 24-hour period Formulation and Stability Mesna for injection is available as 100mg/ml 10ml multidose vials which contain 0.25 mg/mL edetate disodium and sodium hydroxide for pH adjustment. Mesna Injection multidose vials also contain 10.4 mg/ml of benzyl alcohol as a preservative. Store product at controlled room temperature 15-25° C (68 -77ºF). Mesna is not light- sensitive, but is oxidized to DiMesna when exposed to oxygen. Mesna as benzyl alcohol- preserved vials may be stored and used for 8 days. Mesna non-preserved ampoules are no longer provided by Bristol-Myer Squibb Company. Supplier Re-MATC H Protocol Page 70 of 106 Version: 20180628 Commercially available from various manufacturers.