Melphalan hydrochloride (generic versions of Alkeran, which is no longer commercially available in the US) is available as a lyophilized powder in single-use or single-dose vials containing the equivalent of 50 mg of melphalan and povidone 20 mg.3173; 3425; 3426 Each vial is packaged with a 10-mL vial of special diluent containing sodium citrate 0.2 g, propylene glycol 6 mL, alcohol (e.g., ethanol [96%] 0.52 mL,3173 dehydrated alcohol 0.51 mL,3425 ethanol [100%] 0.5 mL),3426 and sterile water for injection.3173; 3425; 3426 The contents of each vial should be reconstituted by rapidly injecting 10 mL of the special diluent into the vial using a syringe with a 20-gauge or larger needle, and the vial should be shaken vigorously until the solution is clear to yield a 5-mg/mL solution of melphalan; rapid addition of the diluent and subsequent vigorous shaking are important for proper dissolution of the drug.3173; 3425; 3426 The appropriate dose of the reconstituted solution should be diluted immediately in sodium chloride 0.9% to a concentration not exceeding 0.45 mg/mL.3173; 3425; 3426
Melphalan hydrochloride (Evomela, Spectrum) also is available as a lyophilized powder in single-dose vials containing the equivalent of 50 mg of melphalan and betadex sulfobutyl ether sodium 2700 mg as a stabilizing excipient.3171; 3172 This formulation is propylene glycol-free.3171; 3172; 3427 The contents of each vial should be reconstituted with 8.6 mL of sodium chloride 0.9% to yield a 5-mg/mL solution of melphalan.3172 The appropriate dose of the reconstituted solution should be withdrawn from the vial and diluted with sodium chloride 0.9% to a concentration of 0.45 mg/mL.3172
Equivalency
Melphalan hydrochloride 56 mg is equivalent to 50 mg of melphalan free base.3172
Trade Name(s)
Alkeran, Evomela
Melphalan hydrochloride is administered intravenously as an infusion.3172; 3173; 3425; 3426 The manufacturers recommend that the drug be administered slowly into a fast-running intravenous infusion solution via a central venous line or injection port.3172; 3173
The final diluted solution of melphalan (generic versions of Alkeran) for infusion is administered over at least 15 minutes (usually 15 to 20 minutes).3173; 3425; 3426
The final diluted solution of melphalan (Evomela) for infusion is administered over 15 to 20 minutes or 30 minutes, depending on the indication.3172
Extravasation of melphalan hydrochloride may cause local tissue damage and should be avoided.3172; 3173; 3425; 3426 The drug should not be administered by direct injection into a peripheral vein.3172; 3173; 3425; 3426 In cases of poor peripheral access, consideration should be given to the use of a central venous line.3173; 3425; 3426
As with other toxic drugs, caution should be exercised in the handling and preparation of melphalan hydrochloride and applicable special handling and disposal procedures should be followed.3172; 3173; 3425; 3426 Some manufacturers recommend the use of gloves as skin reactions may occur with accidental exposure.3173; 3425; 3426 If skin or mucosal contact with the drug occurs, the affected area(s) should be washed immediately and thoroughly with soap and water.3173; 3425; 3426
Intact vials should be stored at controlled room temperature and protected from light;3172; 3173; 3425; 3426 some manufacturers recommend storage in the original carton.3173; 3425
The solution should be visually inspected for particulate matter and discoloration prior to administration; if particulate matter is present or discoloration occurs, the solution should not be used.3172; 3173; 3425; 3426
The reconstituted solution of melphalan (generic versions of Alkeran) should not be refrigerated; a precipitate forms in the reconstituted product if stored at 5°C.3173; 3425; 3426
Melphalan Hydrochloride (generic versions of Alkeran)
The time between reconstitution and dilution and administration of solutions of melphalan (generic versions of Alkeran) should be minimized.3173; 3425; 3426 In as little as 30 minutes from reconstitution, a citrate derivative of melphalan has been detected; upon further dilution with sodium chloride 0.9%, nearly 1% of the drug is hydrolyzed every 10 minutes.3173; 3425; 3426 Manufacturers recommend that administration of melphalan hydrochloride be completed within 60 minutes of reconstitution.3173; 3425; 3426
Melphalan Hydrochloride (Evomela, Spectrum)
The manufacturer states that the 5-mg/mL reconstituted solution of Evomela is stable for 1 hour at room temperature or 24 hours under refrigeration at 5°C without any precipitation because of its high solubility.3172 After dilution of Evomela to a melphalan concentration of 0.45 mg/mL in sodium chloride 0.9%, this formulation is stable for 4 hours at room temperature in addition to the 1 hour at room temperature following reconstitution.3172
One study found that a 5-mg/mL reconstituted solution of melphalan (as the Evomela formulation) was stable for 25 hours at room temperature based on experimental trend analysis and for up to 48 hours when stored at 2 to 8°C.3171; 3427 At 2 to 8°C, the 5-mg/mL reconstituted solution exhibited an antimicrobial effect for up to 72 hours against 8 microorganisms tested in the study (Aspergillus brasiliensis, Candida albicans, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant S. aureus [MRSA], and vancomycin-resistant Enterococcus faecalis [VRE]).3171 Concentrations of 0.45, 1, and 2 mg/mL diluted in sodium chloride 0.9% were calculated to be stable for a time of 4, 7, and 11 hours, respectively, based on experimental trend analysis.3171; 3427
pH Effects
Melphalan is most stable over a pH range of 3 to 7; decomposition increases at pH 9.971
Sorption
Melphalan (GlaxoWellcome) 60 mcg/mL in sodium chloride 0.9% exhibited no loss due to sorption in polyethylene, polyvinyl chloride (PVC) containers, and glass containers over 24 hours under refrigeration and 8 hours at room temperature.2420; 2430
Filtration
Melphalan 20 mcg/mL in 1 mL of sodium chloride 0.9% was filtered through the following filters; minimal adsorption occurred in all cases:970
| Filter | Delivered Concentration (% of initial) |
|---|---|
| Cellulose acetate 0.2 µm (Minisart-N, Sartorius) | 99 |
| Polysulfone 0.45 µm (Acrodisc, Gelman) | 98 |
| Polytetrafluoroethylene 0.45 µm (Acrodisc-CR, Gelman) | 96 |
For a list of references cited in the text of this monograph, search the monograph titled References.