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 The reconstituted solution should be diluted in an infusion bag with an appropriate volume of sodium chloride 0.9% (e.g., 500 mL for thiotepa doses of 250 to 500 mg; 1000 mL for thiotepa doses exceeding 500 mg) to achieve a solution with a final thiotepa concentration of 0.5 to 1 mg/mL.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 The appropriate dose of the reconstituted solution should be diluted with sodium chloride 0.9% prior to administration.3368
pH
The pH of the reconstituted solution of thiotepa has a range of approximately 5.5 to 7.5.3367; 3368
Tonicity
Reconstitution with sterile water for injection results in a hypotonic solution; the reconstituted solution should be diluted in sodium chloride 0.9% prior to use.3367; 3368
Solutions of thiotepa at concentrations of 0.5 and 1 mg/mL in sodium chloride 0.9% are nearly isotonic; solutions of thiotepa at concentrations of 3 and 5 mg/mL in sodium chloride 0.9% are hypotonic.2006
Osmolality
The osmolalities of thiotepa 0.5 and 1 mg/mL in sodium chloride 0.9% are 277 and 269 mOsm/kg, respectively.2006
Trade Name(s)
Tepadina
Thiotepa is administered by rapid intravenous administration or intravenous infusion or by the intracavitary or intravesical route.3367; 3368
The final diluted solution of thiotepa must be filtered prior to administration.3367; 3368 (See Filtration.)
As with other toxic drugs, caution should be exercised in the handling and preparation of thiotepa.3367; 3368 The use of gloves has been recommended as skin reactions may occur with accidental exposure.3368 If skin contact with the solution occurs, the exposed area(s) should be washed thoroughly with soap and water; for mucosal membrane contact, the exposed area(s) should be flushed thoroughly with water.3367; 3368 Procedures for the proper disposal of thiotepa should be considered.3367
Thiotepa is a white powder that forms a clear solution upon reconstitution.3367 One manufacturer notes that reconstituted solutions free of particulate matter may exhibit opalescence; however, such solutions still may be diluted for administration.3367
Intact vials should be stored at 2 to 8°C.3367; 3368 One manufacturer (West-Ward) states that thiotepa should be protected from light at all times.3368 Another manufacturer (Amneal Biosciences) states that thiotepa should not be frozen.3367
The reconstituted solution of thiotepa is stable at 2 to 8°C for 8 hours.3367; 3368 Diluted solutions for infusion should be used immediately;3367; 3368 however, one manufacturer has stated that diluted solutions for infusion are stable for 24 hours at 2 to 8°C or 4 hours at 25°C.3367
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
Thiotepa is stable in alkaline media, but unstable in acidic media,3367; 3368 undergoing increased rates of hydrolysis.1389
Syringes
Thiotepa reconstituted to a concentration of 10 mg/mL with sterile water for injection was found to be stable for 24 hours under refrigeration at 8°C and at room temperature of 23°C in both the original vials and transferred to plastic syringes.2006
Filtration
One manufacturer of thiotepa (Tepadina, Amneal Biosciences) recommends filtration of the diluted solution for infusion through an infusion set containing a 0.2-µm inline filter.3367 Another manufacturer of thiotepa (West-Ward) recommends filtration of the diluted solution for infusion through a 0.22-µm filter (i.e., polysulfone membrane [Sterile Aerodisc, Gelman] or triton-free mixed ester of cellulose/polyvinyl chloride [PVC] [Millex-GS, Millipore]) 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
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.