Hydrocortisone sodium succinate is available in 100-mg conventional vials containing hydrocortisone sodium succinate equivalent to hydrocortisone 100 mg with monobasic sodium phosphate anhydrous 0.8 mg and dibasic sodium phosphate dried 8.73 mg.3683 For intravenous or intramuscular injection, the contents of one vial should be reconstituted by adding not more than 2 mL of bacteriostatic water for injection or bacteriostatic sodium chloride injection.3683 For intravenous infusion, the contents of one vial should be reconstituted by adding not more than 2 mL of bacteriostatic water for injection; the reconstituted solution can then be added to 100 to 1000 mL of a compatible infusion solution (e.g., dextrose 5%, sodium chloride 0.9%, dextrose 5% in sodium chloride 0.9%).3683 Conventional vials of Solu-Cortef do not contain diluent nor is the diluent provided by the manufacturer.3696
The drug also is supplied in single-dose “Act-O-Vial” containers of hydrocortisone sodium succinate equivalent to hydrocortisone 100, 250, 500, and 1000 mg.3683 The pH has been adjusted when necessary with sodium hydroxide.3683 For the “Act-O-Vial” containers, the plastic activator should be pressed down to force the water for injection diluent into the lower chamber.3683 The vial should be agitated gently to dissolve the drug.3683 When reconstituted, each mL of solution contains:3683
| Component | 100 mg | 250, 500, 1000 mg |
|---|---|---|
| Hydrocortisone equivalent (as sodium succinate) | 50 mg | 125 mg |
| Monobasic sodium phosphate anhydrous | 0.4 mg | 1 mg |
| Dibasic sodium phosphate dried | ~4.37 mg | 10.9 to 11 mg |
| Water for injection | qs | qs |
For intravenous or intramuscular injection, reconstituted solutions prepared in “Act-O-Vial” containers do not require further dilution.3683 For intravenous infusion, reconstituted solutions prepared in “Act-O-Vial” containers may then be added to dextrose 5%.3683 In patients not requiring sodium restriction, sodium chloride 0.9% or dextrose 5% in sodium chloride 0.9% also may be used.3683 To prepare the diluted solution for infusion, hydrocortisone doses of 100 mg may be added to 100 to 1000 mL, 250 mg may be added to 250 to 1000 mL, 500 mg may be added to 500 to 1000 mL, and 1000 mg may be added to 1000 mL of a compatible infusion solution.3683 In cases where fluid restriction is desired, hydrocortisone doses of 100 to 3000 mg may be added to 50 mL of a compatible infusion solution.3683
As of 2016, Solu-Cortef products marketed in the United States do not contain benzyl alcohol.3696
pH
The pH of the reconstituted solution ranges from 7 to 8.3683
Osmolality
The osmolality of hydrocortisone sodium succinate (Abbott) at a hydrocortisone concentration of 50 mg/mL was determined to be 292 mOsm/kg by freezing-point depression and 260 mOsm/kg by vapor pressure.1071
Osmolarity
The osmolarity of the reconstituted solution prepared from the 100-mg “Act-O-Vial” container is 360 mOsm/L.3683 The osmolarity of the reconstituted solution prepared from the 250-, 500-, and 1000-mg “Act-O-Vial” containers is 570 mOsm/L.3683
Sodium Content
Hydrocortisone sodium succinate contains 2.066 mEq of sodium per gram of drug.846
Trade Name(s)
Solu-CORTEF
Hydrocortisone sodium succinate may be administered by intramuscular injection, direct intravenous injection over 30 seconds (e.g., 100-mg doses) to 10 minutes (e.g., doses of 500 mg or more), or intravenous infusion at a usual hydrocortisone concentration of 0.1 to 1 mg/mL in a compatible infusion solution.3683
When administered by intramuscular injection, the deltoid muscle should be avoided because of a high incidence of subcutaneous atrophy.3683
Hydrocortisone sodium succinate in intact containers should be stored at a controlled room temperature of 20 to 25°C.3683 After reconstitution, solutions should be stored at a controlled room temperature of 20 to 25°C and protected from light.3683 The solution should only be used if it is clear.3683 Unused solutions should be discarded after 3 days.3683 Hydrocortisone sodium succinate is heat labile and must not be autoclaved.3683
pH Effects
Hydrocortisone sodium succinate is optimally stable at pH 7 to 8. It is stable for 72 hours at pH 6 and for 12 hours at pH 5. More acidic solutions cause precipitation.41
Solutions of hydrocortisone buffered to pH 9.1 showed oxidation to 21-dehydrocortisone at rates of 1.6 to 2.8% per hour at 26°C. This rate is 4 or 5 times greater than that observed at pH 6.9 to 7.9.531
Freezing Solutions
Hydrocortisone sodium succinate (Upjohn) reconstituted solution at a hydrocortisone concentration of 500 mg/4 mL exhibited no loss over 4 weeks when stored frozen.69
Intrathecal Injections
In a study of solutions for intrathecal injection, hydrocortisone sodium succinate (Upjohn) was reconstituted to a hydrocortisone concentration of 1 mg/mL with Elliott’s B solution (295 mOsm/kg, pH 7.3), sodium chloride 0.9% (296 mOsm/kg, pH 7), and Ringer’s injection, lactated (258 mOsm/kg, pH 7). In Ringer’s injection, lactated and sodium chloride 0.9%, no decomposition was observed in 24 hours at room temperature under fluorescent light or at 30°C. However, in 7 days, approximately 10% decomposition occurred at room temperature and about 15% at 30°C. In Elliott’s B solution, hydrocortisone is much less stable. In 24 hours, a 7% loss occurred at room temperature and a 12% loss occurred at 30°C, increasing to 21 and 32%, respectively, at 72 hours. Less than 10% decomposition of this combination occurred in 4 to 8 hours.327
In another study, the stability and compatibility of cytarabine (Upjohn), methotrexate (NCI), and hydrocortisone (Upjohn), mixed together in intrathecal injections, were evaluated. Two combinations were tested: (1) cytarabine 50 mg, methotrexate 12 mg (as the sodium salt), and hydrocortisone 25 mg (as the sodium succinate salt); and (2) cytarabine 30 mg, methotrexate 12 mg (as the sodium salt), and hydrocortisone 15 mg (as the sodium succinate salt). Each drug combination was added to 12 mL of Elliott’s B solution (NCI), sodium chloride 0.9% (Abbott), dextrose 5% (Abbott), and Ringer’s injection, lactated (Abbott) and stored for 24 hours at 25°C. Cytarabine and methotrexate were both chemically stable, with no drug loss after the full 24 hours in all solutions. Hydrocortisone also was stable in the sodium chloride 0.9%, dextrose 5%, and Ringer’s injection, lactated, with about a 2% drug loss. However, in Elliott’s B solution, hydrocortisone was significantly less stable, with a 6% loss in the 25-mg concentration over 24 hours. The 15-mg concentration was worse, with a 5% loss in 10 hours and a 13% loss in 24 hours. The higher pH of Elliott’s B solution and the lower concentration of hydrocortisone may have been factors in this increased decomposition. All mixtures were physically compatible for 24 hours, but a precipitate formed after several days of storage.819
Hydrocortisone sodium succinate (Upjohn) at a hydrocortisone concentration of 2 mg/mL diluted in Elliott’s B solution (Orphan Medical) was packaged as 20 mL in 30-mL glass vials and 20-mL plastic syringes (Becton Dickinson) with Red Cap (Burron) Luer-lok syringe tip caps. The solution was physically compatible and chemically stable exhibiting about 9% or less loss in 24 hours at 23°C and 7% or less loss in 48 hours at 4°C.1976
Bacterially contaminated intrathecal solutions could pose grave risks and, consequently, such solutions should be administered as soon as possible after preparation.328
Syringes
Hydrocortisone sodium succinate (Upjohn) at a hydrocortisone concentration of 10 mg/mL in sodium chloride 0.9% was packaged in polypropylene syringes (Becton Dickinson) and stored under refrigeration at 5°C and at room temperature of 25°C. The drug solution remained clear throughout the study, and about 2% hydrocortisone loss occurred after 21 days under refrigeration. At room temperature, about 5% loss occurred in 3 days and 10% loss occurred in 7 days. Stability in glass containers was found to be comparable.2331
Hydrocortisone sodium succinate (Pharmacia) at a hydrocortisone concentration of 50 mg/mL in sterile water for injection packaged in polypropylene syringes (Braun) was visually compatible with calculated shelf lives of 6.8 days at room temperature and 81 days under refrigeration.2654
Sorption
Hydrocortisone sodium succinate was shown not to exhibit sorption to polyvinyl chloride (PVC) bags and tubing, polyethylene tubing, Silastic tubing, and polypropylene syringes.12; 536; 606
Filtration
Hydrocortisone sodium succinate (Upjohn) at a hydrocortisone concentration of 10 mg/L in dextrose 5% and sodium chloride 0.9% did not display significant sorption to a 0.45-µm cellulose membrane filter (Abbott S-A-I-F) during an 8-hour simulated infusion.567
Central Venous Catheter
Hydrocortisone sodium succinate (Abbott) at a hydrocortisone concentration of 1 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.2335
For a list of references cited in the text of this monograph, search the monograph titled References.