Methylprednisolone sodium succinate is available as a lyophilized powder in multiple-dose vials containing the equivalent of methylprednisolone 500 mg or 1 g and in single-dose vials containing the equivalent of methylprednisolone 2 g.3873 Vials also contain monobasic sodium phosphate anhydrous and dibasic sodium phosphate dried.3873 Sodium hydroxide may have been added to adjust the pH.3873 The 2-g vials may be packaged with a diluent vial containing bacteriostatic water for injection preserved with benzyl alcohol.3873 Each 500-mg or 1-g vial should be reconstituted by adding 8 or 16 mL, respectively, of bacteriostatic water for injection containing benzyl alcohol to yield a solution containing methylprednisolone 62.5 mg/mL.3873 Each 2-g vial should be reconstituted with 30 mL of bacteriostatic water for injection containing benzyl alcohol to yield a solution containing methylprednisolone 65.4 mg/mL.3873
Methylprednisolone sodium succinate also is available as a preservative-free lyophilized powder in a single-dose dual-chamber vial (“Act-O-Vial”) containing the equivalent of methylprednisolone 40 mg (1 mL), 125 mg (2 mL), 500 mg (4 mL), or 1000 mg (8 mL) along with monobasic sodium phosphate anhydrous and dibasic sodium phosphate dried; the 40-mg vial also contains lactose hydrous.3873 Sodium hydroxide may have been added to adjust the pH.3873 To reconstitute the solution in “Act-O-Vial” containers, the plastic activator should be pressed down to force the diluent into the lower chamber.3873 The vial should be agitated gently to dissolve the drug.3873 The reconstituted solutions contain methylprednisolone 40, 62.5, or 125 mg/mL.3873
For intravenous infusion, the reconstituted solution may be diluted in a compatible infusion solution.3873
pH
The pH of the reconstituted solution ranges from 7 to 8.3873
Osmolality
The osmolality of methylprednisolone sodium succinate was calculated for the following dilutions:1054
| Osmolality (mOsm/kg) | ||
|---|---|---|
| Methylprednisolone in Diluent | 50 mL | 100 mL |
| 500 mg in Dextrose 5% | 291 | 275 |
| 500 mg in Sodium chloride 0.9% | 317 | 301 |
| 1 g in Dextrose 5% | 318 | 292 |
| 1 g in Sodium chloride 0.9% | 345 | 319 |
Sodium Content
Each gram of methylprednisolone sodium succinate contains 2.01 mEq of sodium.846
Trade Name(s)
A-MethaPred, SOLU-Medrol
Methylprednisolone sodium succinate may be administered by intramuscular injection, direct intravenous injection, or by intravenous infusion.3873
Direct intravenous injection should be administered over several minutes.3873 High-dose therapy is recommended to be given at doses of 30 mg/kg intravenously over at least 30 minutes and may be repeated.3873 Cardiac arrhythmia and/or cardiac arrest have been reported with rapid intravenous administration of large doses (e.g., greater than 500 mg administered over a period of less than 10 minutes).3873
Intact vials of methylprednisolone sodium succinate should be stored at controlled room temperature and protected from light.3873 Reconstituted solutions also should be stored at controlled room temperature, protected from light, and should be used within 48 hours.3873 Unused portions of single- and multiple-dose vials should be discarded.3873
The manufacturer states diluted solutions in dextrose 5%, sodium chloride 0.9%, or dextrose 5% in sodium chloride 0.9% are stable for 4 hours if stored below 25°C or 24 hours if stored at 2 to 8°C.3873
The drug is subject to both ester hydrolysis and acyl migration. Degradation products include free methylprednisolone, succinate, and methylprednisolone-17-succinate.1072 Gross decomposition may result in insoluble free methylprednisolone.2426 Solutions should be visually inspected for particulate matter and discoloration prior to administration.3873
Methylprednisolone sodium succinate (Upjohn) diluted to a concentration of 4 mg/mL with sterile water for injection and packaged in glass vials was evaluated for stability. The samples stored at 22°C lost 10% in 24 hours while those stored at 4°C lost 6% in 7 days and 17% in 14 days.1938
pH Effects
The minimum rate of hydrolysis occurs at pH 3.5. Between pH 3.4 and 7.4, acyl migration is the dominant effect.1501
Freezing Solutions
Reconstituted methylprednisolone sodium succinate (Upjohn) 125 mg/2 mL, when stored frozen, exhibited no loss over 4 weeks.69
When stored frozen at -20°C, methylprednisolone sodium succinate (Upjohn) 500 mg/108 mL in sodium chloride 0.9% in polyvinyl chloride (PVC) bags exhibited no loss after 12 months followed by microwave thawing. Furthermore, the solution was physically compatible.1612
Syringes
Methylprednisolone sodium succinate (Pharmacia & Upjohn) 10 mg/mL in sodium chloride 0.9% was packaged in 10-mL polypropylene syringes (Becton Dickinson) and 12-mL polypropylene syringes (Monoject) and stored at 5 and 25°C. The drug solutions remained clear, and about 10% loss occurred in 7 days at 25°C and about 4% loss in 21 days at 5°C. The losses were comparable to the drug solution stored in a glass flask, indicating sorption to syringe components did not occur.2340
Central Venous Catheter
Methylprednisolone sodium succinate (Abbott) 5 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
Autoclaving
Methylprednisolone sodium succinate is heat sensitive; vials should not be autoclaved.3873
Drugs in Syringe Compatibility
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Infusion Solutions
Solution haziness was reported for methylprednisolone sodium succinate admixtures in intravenous fluids.702; 758 Changes in the manufacturing process for bulk methylprednisolone sodium succinate powder have resulted in substantial improvements in admixture clarity and absence of the haze formation that developed previously in solutions of Solu-Medrol.670; 702
In a study of the turbidity produced by methylprednisolone sodium succinate (Abbott) 500 mg to 30 g/L, turbidity was substantially higher in dextrose 5% than in sodium chloride 0.9%.758 Another important factor was the concentration of methylprednisolone sodium succinate. Turbidity was generally higher at intermediate concentrations (2 to 15 g/L) than at low (300 mg/L) or high (20 g/L) concentrations.758
These differences in the development of turbidity cannot be explained by simple increased ester hydrolysis due to differing pH values and drug concentrations. Rather, the solubility of free methylprednisolone in various concentrations of methylprednisolone sodium succinate has been suggested as the primary factor. The solubility of free methylprednisolone is increased as the concentration of the sodium succinate ester increases. The increased solubilization is believed to overshadow increased formation of free methylprednisolone in concentrations over 10 g/L, preventing or minimizing precipitation and turbidity. Differences in turbidity between the drug in dextrose 5% and sodium chloride 0.9% are believed to result primarily from the electrolyte content of sodium chloride 0.9% and, to a much lesser extent, the pH of the dextrose admixtures. These differences are presumed to affect the solubilizing capacity and reactivity of the ester.758
Other Drugs
The compatibility of methylprednisolone sodium succinate (Upjohn) with several drugs added to auxiliary medication infusion units has been studied. Primary admixtures were prepared by adding various drugs to dextrose 5%, dextrose 5% in sodium chloride 0.9%, and Ringer’s injection, lactated. Up to 100 mL of the primary admixture was added along with methylprednisolone sodium succinate (Upjohn) to the auxiliary medication infusion unit with the following results:329
| Methylprednisolone Sodium Succinate | Primary Solution | Result |
|---|---|---|
| Aminophylline 500 mg/L | ||
| 500 mg | D5S, D5W qs 100 mL | Clear solution for 24 hr |
| 500 mg | LR qs 100 mL | Clear solution for 24 hr |
| 500 mg | Added to 100 mL LR | Clear solution for 1 hr |
| 1000 mg | D5W qs 100 mL | Yellow solution, clear for 24 hr |
| 1000 mg | D5S qs 100 mL | Yellow solution, clear for 6 hr |
| 1000 mg | Added to 100 mL D5S | Yellow solution, clear for 24 hr |
| 1000 mg | LR qs 100 mL or added to 100 mL LR | Yellow solution, clear for 4 hr |
| 2000 mg | D5S, D5W, LR qs 100 mL | Yellow solution, clear for 24 hr |
| Heparin Sodium 10,000 units/L | ||
| 500 mg | D5S, D5W qs 100 mL | Clear solution for 24 hr |
| 500 mg | LR qs 100 mL or added to 100 mL LR | Clear solution for 6 hr |
| 1000 mg | D5S, D5W qs 100 mL | Clear solution for 6 hr |
| 1000 mg | Added to 100 mL D5W | Clear solution for 24 hr |
| 1000 mg | LR qs 100 mL or added to 100 mL LR | Clear solution for 4 to 6 hr |
| 2000 mg | D5W qs 100 mL | Clear solution for 6 hr |
| 2000 mg | D5S, LR qs 100 mL | Clear solution for 24 hr |
| Potassium Chloride 40 mEq/L | ||
| 500 mg | D5S, D5W, LR qs 100 mL | Clear solution for 24 hr |
| 1000 mg | D5W qs 100 mL | Clear solution for 24 hr |
| 1000 mg | D5S, LR qs 100 mL or added to 100 mL D5S, LR | Clear solution for 6 hr |
| 2000 mg | D5S, D5W, LR qs 100 mL | Clear solution for 24 hr |
| Sodium Bicarbonate 44.6 mEq/L | ||
| 500 mg | D5S, D5W qs 100 mL | Clear solution for 24 hr |
| 500 mg | LR qs 100 mL or added to 100 mL LR | Clear solution for 1 hr |
| 1000 mg | D5W qs 100 mL | Clear solution for 24 hr |
| 1000 mg | D5S qs 100 mL or added to 100 mL D5S | Clear solution for 24 hr |
| 1000 mg | LR qs 100 mL | Clear solution for 1 hr |
| 1000 mg | Added to 100 mL LR | Clear solution for 4 hr |
| 2000 mg | D5S, D5W qs 100 mL | Clear solution for 24 hr |
| 2000 mg | LR qs 100 mL | Clear solution for 30 min |
| 2000 mg | Added to 100 mL LR | Clear solution for 4 hr |
For a list of references cited in the text of this monograph, search the monograph titled References.