Gemcitabine hydrochloride is available as a lyophilized powder in single-dose (preservative-free) vials containing 200 mg, 1 g, or 2 g of drug (as the base).3526; 3527 For each 200 mg of gemcitabine lyophilized powder contained in each vial, mannitol 200 mg and sodium acetate 12.5 mg also are present.3526; 3527 The contents of the 200-mg, 1-g, and 2-g vials should be reconstituted with 5, 25, and 50 mL, respectively, of sodium chloride 0.9% and shaken to dissolve the powder to yield a solution with a gemcitabine concentration of 38 mg/mL.3526; 3527 Prior to administration, the appropriate dose of the reconstituted solution should be diluted with sodium chloride 0.9% to a final gemcitabine concentration of not less than 0.1 mg/mL.3526; 3527
Gemcitabine hydrochloride also is available as a concentrate for injection.3528; 3529 In 200-mg, 1-g, and 2-g single-dose vials, each mL of the concentrate contains 38 mg of gemcitabine in water for injection.3529 In 200-mg and 1-, 1.5-, and 2-g multidose vials, each mL of the concentrate for injection contains 100 mg of gemcitabine, 250 mg of polyethylene glycol (PEG) 300, 150 mg of propylene glycol, and 16 mg of sodium hydroxide in dehydrated alcohol.3528 Prior to administration, the appropriate dose of the concentrate for injection must be diluted with sodium chloride 0.9% to a final gemcitabine concentration of not less than 0.1 mg/mL.3528; 3529 The diluted solution should be mixed by gentle inversion and should not be shaken.3528
Gemcitabine hydrochloride also is available as a premixed, ready-to-use solution for infusion in single-dose bags containing 120, 130, 140, 150, 160, 170, 180, 190, 200, and 220 mL.3530 Each 100 mL of the ready-to-use solution for infusion contains 1 g of gemcitabine and 900 mg of sodium chloride in water for injection.3530 The ready-to-use solution for infusion should not be further diluted and should not be used in patients requiring less than the entire dose of a single-dose bag.3530
The pH of all of the gemcitabine products may have been adjusted by the manufacturers with sodium hydroxide and/or hydrochloric acid.3526; 3527; 3528; 3529; 3530
Solutions of gemcitabine (e.g., reconstituted solutions, commercially available solutions, solutions diluted for infusion, commercially available solutions for infusion) should be inspected for particulate matter and discoloration prior to administration; if particulate matter is present or discoloration has occurred, solutions should be discarded.3526; 3527; 3528; 3529; 3530
Equivalency
Gemcitabine hydrochloride 113.85 mg is equivalent to 100 mg of gemcitabine base.3527; 3528; 3529; 3530
Trade Name(s)
Gemzar, Infugem
Gemcitabine hydrochloride is administered by intravenous infusion over 30 minutes.3526; 3527; 3528; 3529; 3530 When 2 bags of the premixed, ready-to-use solution for infusion are required to achieve the appropriate dose, the combined volume of both infusion bags should be infused over 30 minutes.3530 Prolongation of the infusion time of gemcitabine hydrochloride beyond 60 minutes has resulted in an increased incidence of adverse effects.3526; 3527; 3528; 3529; 3530
As with other toxic drugs, caution should be exercised in the handling and preparation of gemcitabine hydrochloride and applicable special handling and disposal procedures should be followed.3526; 3527; 3528; 3529; 3530 Gloves are recommended to be worn in the preparation of the drug.3526; 3527; 3528; 3529; 3530 If skin or mucosal contact with the drug occurs, the affected area(s) should be washed immediately and thoroughly with copious amounts of water.3526; 3527; 3528; 3529; 3530
Gemcitabine hydrochloride is a white to off-white lyophilized powder that forms a clear, colorless to light straw-colored solution upon reconstitution.3526; 3527 Intact vials of gemcitabine hydrochloride should be stored at controlled room temperature.3526; 3527 Manufacturers state that reconstituted and diluted solutions for infusion prepared from the lyophilized powder may be stored at controlled room temperature for up to 24 hours; solutions not used within 24 hours after reconstitution should be discarded.3526; 3527 However, other information indicates the reconstituted solution may be stable for longer periods.2227 (See Reconstituted Solutions). Manufacturers state that reconstituted and diluted solutions of gemcitabine hydrochloride should not be refrigerated because crystallization may occur.3526; 3527
Gemcitabine hydrochloride concentrate for injection is a clear, colorless to pale yellow3528 or light straw-colored3529 solution. Intact multidose vials of gemcitabine hydrochloride concentrate for injection should be stored at controlled room temperature.3528 Multidose vials are stable for up to 28 days from initial vial puncture when stored at room temperature.3528 Intact single-dose vials of gemcitabine hydrochloride concentrate for injection should be stored at 2 to 8°C and should not be frozen.3529 Manufacturers state that diluted solutions for infusion prepared from the concentrate for injection may be stored at controlled room temperature for up to 24 hours; solutions not used within 24 hours after dilution should be discarded.3528; 3529
Gemcitabine hydrochloride premixed, ready-to-use solution for infusion is a clear, colorless solution.3530 Intact containers should be stored at controlled room temperature.3530 The solution should not be frozen because crystallization may occur.3530
Gemcitabine hydrochloride (Lilly) 2.4 mg/mL diluted in sodium chloride 0.9% and stored at 22°C did not exhibit a substantial antimicrobial effect on the growth of 4 organisms (Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) inoculated into the solution. C. albicans maintained viability for 120 hours, and the others were viable for 24 hours. The author recommended that diluted solutions of gemcitabine hydrochloride be stored under refrigeration whenever possible and that the potential for microbiological growth should be considered when assigning expiration periods.2160
Reconstituted Solutions
The contents of gemcitabine hydrochloride (Lilly) 200-mg and 1-g vials were reconstituted to a gemcitabine concentration of 38 mg/mL with sterile water for injection and also sodium chloride 0.9% in the original vials and evaluated over periods of 35 days at 23°C exposed to and protected from fluorescent light and at 4°C protected from light.2227 The samples stored at 23°C were physically stable throughout the study period.2227 Under 4% loss occurred in 35 days at 23°C.2227 When refrigerated, the solutions remained physically and chemically stable for at least 7 days, but large colorless crystals formed in some samples after that time.2227 The crystals did not redissolve on warming to room temperature.2227 No loss occurred in the refrigerated solutions unless crystals formed; gemcitabine losses of 20 to 35% were determined in samples containing crystals.2227 Exposure to or protection from fluorescent light did not affect gemcitabine stability.2227
Syringes
Gemcitabine hydrochloride (Lilly) 38 mg/mL in sodium chloride 0.9% was repackaged as 10 mL of solution in 20-mL plastic syringes (Becton Dickinson) and sealed with tip caps (Red Cap, Burron).2227 Sample syringes were stored at 23°C both exposed to and protected from fluorescent light and at 4°C protected from light for 35 days.2227 All samples were physically stable throughout the study period.2227 Although not observed in the solutions packaged in plastic syringes in this study,2227 crystallization can occur in reconstituted solutions stored under refrigeration.3526; 3527 Little to no loss occurred in 35 days under any of the conditions.2227
Sorption
Gemcitabine hydrochloride has not exhibited any incompatibilities with bottles or polyvinyl chloride (PVC) bags and administration sets.3526; 3527; 3528; 3529
Gemcitabine hydrochloride (Lilly) 5.12 mg/mL in sodium chloride 0.9% exhibited no loss due to sorption in polyethylene and PVC containers compared to glass containers over 48 hours at room temperature.2420; 2430
For a list of references cited in the text of this monograph, search the monograph titled References.