Temsirolimus is available in a 2-vial kit: the first single-use vial contains temsirolimus concentrate for injection and the second single-use vial contains 1.8 mL of special diluent.3205 Each vial of temsirolimus concentrate for injection contains temsirolimus 25 mg/mL, dehydrated alcohol 39.5% (w/v), dl-alpha-tocopherol 0.075% (w/v), propylene glycol 50.3% (w/v), and anhydrous citric acid 0.0025% (w/v).3205 Each vial of special diluent contains polysorbate 80 40% (w/v), polyethylene glycol 400 42.8% (w/v), and dehydrated alcohol 19.9% (w/v).3205 Both the temsirolimus concentrate for injection vial and the accompanying diluent vial contain an overfill.3205
Preparation of the final diluted solution for infusion from this 2-vial kit requires a 2-step dilution procedure prior to administration.3205 Step 1 is the preparation of the initial diluted solution, which is then further diluted to the final diluted solution for infusion in step 2.3205 During handling and preparation of temsirolimus admixtures, the drug should be protected from excessive room light and sunlight.3205
To prepare the initial diluted solution (step 1), 1.8 mL of the special diluent should be withdrawn from the vial of accompanying diluent and added to the vial of temsirolimus concentrate for injection.3205 Each vial of diluted temsirolimus concentrate for injection should be mixed well by inverting the vial.3205 This initial diluted solution is a clear to slightly turbid, colorless to light yellow solution, essentially free from visual particulates, having a temsirolimus concentration of 10 mg/mL (30 mg/3 mL) and an alcohol content of 35.2%.3205 The vial should be allowed to stand for a sufficient time to allow air bubbles created during mixing to subside.3205
To prepare the final diluted solution (step 2), the appropriate dose of the temsirolimus 10-mg/mL initial diluted solution should be withdrawn from the vial and added to a glass or plastic (e.g., polypropylene, polyolefin) container of 250 mL of sodium chloride 0.9%.3205 The final diluted solution for infusion should be mixed by inversion of the infusion container; excessive shaking should be avoided as it may cause foaming.3205 Solutions should be visually inspected for particulate matter and discoloration prior to administration.3205
Trade Name(s)
Torisel
Temsirolimus is administered as an intravenous infusion over 30 to 60 minutes, preferably using an infusion pump, to patients who have been adequately premedicated to control adverse effects.3205 To minimize patient exposure to the diethylhexyl phthalate (DEHP) plasticizer, the final diluted solution for infusion should be administered using non-DEHP plasticized non-polyvinyl chloride (non-PVC) (e.g., polyethylene-lined) administration sets containing an appropriate filter.3205 (See Filtration.) If a PVC administration set must be used, it should not contain DEHP.3205
Intact vials of temsirolimus concentrate for injection and special diluent contained in the kit should be stored at 2 to 8°C and protected from light.3205
Temsirolimus concentrate for injection is a clear, colorless to light yellow solution.3205 The initial diluted solution is stable for up to 24 hours at temperatures less than 25°C.3205 Once the initial diluted solution has been further diluted with sodium chloride 0.9% to the final diluted solution for infusion, administration should be completed within 6 hours of preparation of the final diluted solution for infusion.3205 The final diluted solution for infusion should be protected from excessive room light and sunlight.3205
pH Effects
Temsirolimus is degraded by both acids and bases; combinations of temsirolimus with agents capable of affecting the solution pH should be avoided.3205
Light Effects
Temsirolimus is light sensitive.3214 Intact vials, as well as the final diluted solution for infusion, should be protected from light.3205 The drug also should be protected from excessive room light and sunlight during handling and preparation of temsirolimus admixtures.3205
Temsirolimus diluted for infusion in polypropylene containers protected from light was infused through a 1.85-m length of non-DEHP PVC-lined intravenous infusion tubing (Intrafix Safe Set, B. Braun) either protected from room light (with aluminum foil) or unprotected over a period of 45 minutes at room temperature.3214 No substantial degradation of temsirolimus was noted following simulated infusion of the diluted solution through tubing with or without light exposure.3214
Plasticizer Leaching
Polysorbate 80 contained in the temsirolimus initial diluted solution and the final diluted solution for infusion can increase the rate at which plasticizer is leached from DEHP-plasticized PVC containers and administration sets.3205 The duration of contact of the diluted drug with PVC during preparation and administration of the drug should be considered.3205 To minimize patient exposure to the plasticizer, the final diluted solution for infusion should be stored in glass or plastic (e.g., polypropylene, polyolefin) containers and infused using polyethylene-lined administration sets.3205 If a PVC administration set must be used, it should not contain DEHP.3205
Filtration
The manufacturer recommends the use of an inline polyethersulfone filter with a pore size not exceeding 5 µm for administration.3205 If the available administration set does not contain an inline filter, an endline polyethersulfone filter should be added to the set prior to drug administration.3205 Different endline filters ranging in pore size from 0.2 to 5 µm may be used; however, the manufacturer does not recommend the use of both an inline and endline filter.3205
For a list of references cited in the text of this monograph, search the monograph titled References.