See package insert for more detailed information. Re-MATC H Protocol Page 74 of 106 Version: 20180628 Toxicities Re-MATC H Protocol Page 75 of 106 Version: 20180628 18.7 Thiotepa Source and Pharmacology Thiotepa (Tespa, Thiophosphamide, Triethylenethiophosphoramide Tspa, WR - 45312) NSC #6396 (032006) is a cytotoxic agent of the polyfunctional type, related chemically and pharmacologically to nitrogen mustard. The radiomimetic action of thiotepa is believed to occur through the release of ethylenimine radicals which, like irradiation, disrupt the bonds of DNA. One of the principal bond disruptions is initiated by alkylation of guanine at the N -7 position, which severs the linkage between the purine base and the sugar and liberates alkylated guanines. Thiotepa is desulfurated by cytochrome P -450 enzymes such as 2B1 and 2C11 which catalyze the conversion of thiotepa to tepa. Tepa is less toxic than thiotepa and has been demonstrated to produce alkali - labile sites in DNA, rather than cross -links. These findings indicate that tepa reacts differently from thiotepa and produces monofunctional alkylation of DNA. A second metabolite of thiotepa, a mercapturic acid conjugate, is formed via glutathione conjugation. Monochloro tepa is the third metabolite found in the urine. Following short intravenous infusion (less than 5 minutes), peak concentrations of thiotepa were measured within 5 minutes. At steady state, the volume of distribution was independent of dose and ranged from 0.3 to 1.6 liters per kilogram (l/kg). Approximately 4.2% of the original d ose is eliminated in the urine within 24 hours as tepa. The elimination half -life of thiotepa ranges from 2.3 to 2.4 hours. The half -life of tepa ranged from 3.0 to 21.1 hours in one study. Formulation and Stability Thiotepa for Injection USP, for single use only, is available in vials containing 15 mg of nonpyrogenic, sterile lyophilized powder. Store in a refrigerator at 2° to 8°C (36° to 46°F).PROTECT FROM LIGHT AT ALL TIMES .