The fixed combination of trimethoprim-sulfamethoxazole is available as a concentrate for injection containing 16 mg of trimethoprim and 80 mg of sulfamethoxazole per mL in 5-, 10-, and 30-mL vials.3715; 3716 Each mL also contains propylene glycol 400 mg, dehydrated alcohol (ethanol) 100 mg, diethanolamine 3 mg, benzyl alcohol 10 mg, and sodium metabisulfite 1 mg in water for injection.3715; 3716 Sodium hydroxide and/or hydrochloric acid may have been added to adjust the pH.3715; 3716
Trimethoprim-sulfamethoxazole concentrate for injection must be diluted in dextrose 5% prior to administration.3715; 3716 It is recommended that each 5 mL of the concentrate be added to 125 mL of dextrose 5%; alternatively, 5 mL of the concentrate may be added to 100 or 75 mL (if fluid restriction is required) of dextrose 5%.3715; 3716
pH
Trimethoprim-sulfamethoxazole concentrate for injection has a pH of 9.5 to 10.5.3715; 3716
Osmolality
The osmolalities of trimethoprim-sulfamethoxazole (Burroughs Wellcome) in concentrations of 0.8 + 4, 1.1 + 5.5, and 1.6 + 8 mg/mL in dextrose 5% were determined to be 541, 669, and 798 mOsm/kg, respectively.1375 At 1.6 + 8 mg/mL in sodium chloride 0.9%, the osmolality was determined to be 833 mOsm/kg.1375
Trade Name(s)
Bactrim
Trimethoprim-sulfamethoxazole is administered by intravenous infusion only after dilution in dextrose 5%.3715; 3716 The drug should not be injected intramuscularly.3715; 3716 Infusion over 60 to 90 minutes is recommended; rapid or direct intravenous injection must not be used.3715; 3716
Trimethoprim-sulfamethoxazole concentrate for injection is a clear, colorless to slightly yellow solution.3715; 3716 Intact vials should be stored at controlled room temperature and not refrigerated.3715; 3716 The contents must be used within 48 hours of initial vial entry.3715; 3716
The solubility of trimethoprim in aqueous solutions is partially dependent on the pH of the solution.553 Trimethoprim is a weak base, and its solubility is lower in solutions with a more alkaline pH.553 Precipitation occurs in the diluted infusion solution in varying time periods, depending on the final concentration.553
For dilutions of 5 mL in 125 mL of dextrose 5% (trimethoprim 615 mg/L, sulfamethoxazole 3.08 g/L), use within 6 hours is recommended.3715; 3716 For dilutions of 5 mL in 100 mL of dextrose 5% (trimethoprim 762 mg/L, sulfamethoxazole 3.81 g/L), use within 4 hours is recommended.3715; 3716 For dilutions of 5 mL in 75 mL of dextrose 5% (trimethoprim 1 g/L, sulfamethoxazole 5 g/L), use within 2 hours is recommended.3715; 3716 Solutions should be visually inspected for particulate matter and discoloration prior to administration; if cloudiness or crystallization is present, the solution should not be used and should be discarded.3715; 3716 Infusion admixtures in dextrose 5% should not be refrigerated.3715; 3716
The nature of the precipitate that formed 24 hours after dilution of trimethoprim-sulfamethoxazole (Roche) in 7 infusion solutions was evaluated.1895 In all cases, the sulfamethoxazole concentrations were within 5% of expected values, but the trimethoprim concentrations dropped to about 30% of the initial values.1895 Further evaluation of the solid phases showed them to be trimethoprim alone or with trimethoprim monohydrate.1895
The manufacturers state that trimethoprim-sulfamethoxazole concentrate for injection diluted in dextrose 5% should not be mixed with other drugs or solutions in the same container.3715; 3716
Trimethoprim-sulfamethoxazole solutions are stated to be compatible with glass, polyvinyl chloride (PVC), and polyolefin containers;3715; 3716 the manufacturers state that other materials have not been tested and cannot be recommended.3715; 3716
Syringes
Undiluted trimethoprim-sulfamethoxazole (Elkins-Sinn) 16 + 80 mg/mL was stored in polypropylene syringes (Becton Dickinson) for 2.5 days at room temperature.1582 The syringes were exposed to fluorescent light during the day but kept in the dark at night.1582 No loss was observed at 60 hours.1582
Sorption
Trimethoprim was shown not to exhibit sorption to PVC bags and tubing, polyethylene tubing, Silastic tubing, and polypropylene syringes.536; 606
Plasticizer Leaching
Trimethoprim-sulfamethoxazole (Elkins-Sinn) 0.8 + 4 mg/mL in dextrose 5% did not leach diethylhexyl phthalate (DEHP) plasticizer from 50-mL PVC bags in 24 hours at 24°C.1683
Filtration
Filtration of dilutions of trimethoprim-sulfamethoxazole (Roche), ranging from 1:25 (v/v) to 1:10 (v/v) in several common intravenous infusion solutions, did not appear to result in loss of either drug because of sorption to the filter (Millex-GS, Millipore).747 Filtration of a visibly precipitated solution resulted in a substantial loss of trimethoprim.747
Trimethoprim-sulfamethoxazole (Roche) 1.88 mg/mL in dextrose 5% and sodium chloride 0.9% was filtered through a 0.22-µm cellulose ester membrane filter (Ivex-HP, Millipore) over 6 hours. No significant drug loss due to binding to the filter was noted.1034
For a list of references cited in the text of this monograph, search the monograph titled References.