Thiotepa is available as a lyophilized powder in single-dose vials containing 15 or 100 mg of the drug.3367 The contents of the 15- or 100-mg vials should be reconstituted with 1.5 or 10 mL, respectively, of sterile water for injection and mixed manually by repeated inversions.3367 Each mL of the reconstituted solutions contains 10 mg of thiotepa.3367 For intravenous infusion, the appropriate dose of the reconstituted solution should be diluted in sodium chloride 0.9% in an infusion bag to a final thiotepa concentration of 0.5 to 1 mg/mL (e.g., 500 mL for thiotepa doses of 250 to 500 mg; 1000 mL for thiotepa doses exceeding 500 mg).3367
Thiotepa also is available as a lyophilized powder in single-dose vials labeled as containing 15 mg of the drug.3368 The vial contents should be reconstituted with 1.5 mL of sterile water for injection.3368 Vials contain a slight overfill to allow for a withdrawable volume of about 1.4 mL (about 14.7 mg) of the reconstituted solution with an approximate concentration of 10.4 mg/mL.3368 For intravenous infusion, the appropriate dose of the reconstituted solution should be diluted with sodium chloride 0.9% prior to administration.3368
Thiotepa also is available as a 10-mg/mL concentrate for injection in 1.5-mL single-dose vials.4069 Each vial of concentrate contains 15 mg of thiotepa in polyethylene glycol 400 1.7 g.4069 For intravenous infusion, the appropriate dose of the concentrate should be diluted in sodium chloride 0.9% in an infusion bag to a final thiotepa concentration of 0.5 to 1 mg/mL.4069
pH
Reconstituted solution and concentrate diluted in water: Approximately 5.5 to 7.5.3367; 3368; 4069
Tonicity
Reconstituted solutions are hypotonic and must be diluted in sodium chloride 0.9% prior to administration.3367; 3368
Trade Name(s)
Tepadina, Tepylute
Thiotepa is administered by rapid intravenous administration or intravenous infusion or by the intracavitary or intravesical route.3367; 3368 Solutions prepared from the concentrate are intended only for intravenous infusion.4069
Final diluted solutions of thiotepa must be filtered prior to administration.3367; 3368; 4069 (See Filtration.)
As with other toxic drugs, caution should be exercised in the handling and preparation of thiotepa and applicable special handling and disposal procedures should be followed.3367; 3368; 4069
Thiotepa lyophilized powder is a white powder that forms a clear solution upon reconstitution.3367 Reconstituted solutions free of particulate matter may exhibit opalescence; however, such solutions still may be diluted for administration.3367
Thiotepa concentrate for injection is a clear, colorless or almost colorless solution.4069
Intact vials of the powder or the concentrate should be stored at 2 to 8°C.3367; 3368; 4069 Product labeling may state to protect from light.3368 Do not freeze.3367; 4069
Product labeling states reconstituted solutions are stable for 8 hours at 2 to 8°C.3367; 3368 In one study, reconstituted solutions of thiotepa (Esteve) exhibited little to no loss in 14 days at 2 to 8°C protected from light or 3 days at 25°C in daylight and 60% air humidity.4070
Diluted solutions prepared from the powder or concentrate, if not used immediately, are stated to be stable for 24 hours when stored at 2 to 8°C or 4 hours when stored at 25°C.3367; 4069
Thiotepa may undergo polymerization forming insoluble derivatives.1369 Solutions should be visually inspected for particulate matter and discoloration prior to administration; diluted solutions should be used only if free of visible particulate matter.3367; 3368; 4069
pH Effects
Thiotepa is stable in alkaline media, but unstable in acidic media,3367; 3368; 4069 undergoing increased rates of hydrolysis.1389
Temperature Effects
Degradation of thiotepa is temperature dependent.4070 Thiotepa (Esteve), as 10-mg/mL reconstituted solution or as further diluted solutions of 1, 2, and 3 mg/mL in dextrose 5% or sodium chloride 0.9%, exhibited little to no thiotepa loss in 14 days when refrigerated at 2 to 8°C, protected from light.4070 However, when stored at 25°C in 24-hour daylight and 60% air humidity, the reconstituted solution exhibited over 5% loss in 5 days with degradation products exceeding USP specifications by 7 days.4070 Under the 25°C storage conditions, diluted solutions of thiotepa 1, 2, or 3 mg/mL in dextrose 5% exhibited over 5% loss of thiotepa in 5, 7, or 14 days, respectively, with degradation products exceeding USP specifications as early as 3 days.4070 Diluted solutions of thiotepa 1, 2, or 3 mg/mL in sodium chloride 0.9% under the 25°C storage conditions exhibited over 5% loss of thiotepa in 7, 14, or 14 days, respectively, with substantial formation of chloro-adduct degradation products.4070
Filtration
Final diluted solutions of thiotepa must be filtered through a 0.2-µm filter prior to administration.3367; 4069
One manufacturer (Hikma, formerly West-Ward) recommends filtration of the diluted solution through a 0.22-µm polysulfone membrane (Sterile Aerodisc, Gelman) or triton-free mixed ester of cellulose/PVC (Millex-GS, Millipore) filter to eliminate haze; solutions that remain opaque or precipitate after such filtration should not be used.3368 Filtration of thiotepa does not alter potency.3367; 3368; 4069
Thiotepa 10 to 300 mcg/mL exhibited no loss due to sorption to either cellulose nitrate/cellulose acetate ester (Millex OR) or Teflon (Millex FG) filters.1415; 1416
For a list of references cited in the text of this monograph, search the monograph titled References.