AHFS Class:

8:12.28.12 Cyclic Lipopeptides

Several different formulations of daptomycin are available; the formulations differ in storage requirements, directions for reconstitution and dilution, and stability following reconstitution or dilution.³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸² Specific product labeling should be consulted for additional details.³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸²

Daptomycin is available as a lyophilized powder or cake in single-dose vials containing daptomycin 350 or 500 mg with sodium hydroxide to adjust the pH (Merck, Sagent).³²²²; ³⁷⁸² Some formulations may also contain citric acid 53.8 or 76.8 mg in each 350- or 500-mg vial, respectively (Hospira).³⁷⁸⁰ Formulations with sodium hydroxide should be reconstituted only with sodium chloride 0.9%.³²²²; ³⁷⁸⁰; ³⁷⁸² Each 350- or 500-mg vial should be reconstituted slowly with 7 or 10 mL, respectively, of sodium chloride 0.9% and gently rotated or swirled to ensure complete dissolution.³²²²; ³⁷⁸⁰; ³⁷⁸² Some manufacturers recommend using a beveled, 21-gauge or smaller transfer needle or a needleless device to direct the stream of diluent against the vial wall and then gently rotating the vial to ensure that all of the daptomycin powder becomes wetted.³²²²; ³⁷⁸² The reconstituted vial should be allowed to stand undisturbed for 10 minutes before gently rotating or swirling to ensure complete dissolution.³²²²; ³⁷⁸² Vigorous agitation or shaking of the vial should be avoided to minimize foaming.³²²²; ³⁷⁸⁰; ³⁷⁸² The reconstituted solution has a daptomycin concentration of 50 mg/mL.³²²²; ³⁷⁸⁰; ³⁷⁸²

Daptomycin also is available as a lyophilized powder or cake in single-dose vials containing daptomycin 350 or 500 mg with L-arginine, L-histidine, and L-isoleucine as excipients with hydrochloric acid to adjust the pH (Hikma).³⁴³¹ The formulation with arginine, histidine, and isoleucine should be reconstituted with sterile water for injection or bacteriostatic water for injection only.³⁴³¹ Do not reconstitute this formulation with saline-based diluents because the resulting hyperosmotic solution can cause infusion site reactions if administered as an intravenous injection over 2 minutes.³⁴³¹ Each 350- or 500-mg vial should be reconstituted with 7 or 10 mL, respectively, of sterile water for injection or bacteriostatic water for injection using a beveled, 21-gauge or smaller transfer needle to yield a solution containing daptomycin 50 mg/mL.³⁴³¹ Direct the stream of diluent toward the vial wall and gently rotate or swirl the contents to ensure complete dissolution.³⁴³¹

Daptomycin also is available as a frozen premixed infusion solution in single-dose Galaxy plastic containers containing daptomycin in sodium chloride 350 mg in 50 mL, 500 mg in 50 mL, 700 mg in 100 mL, or 1 g in 100 mL.³⁴³² Monobasic sodium phosphate and dibasic sodium phosphate have been added as buffer agents and hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment.³⁴³² These containers are not recommended for use when the dose required does not equal the full dose supplied in the container.³⁴³²

Other formulations previously available in the United States (Cubicin RF, Dapzura RT) were withdrawn from the market in 2023.³²²¹; ³⁷⁸¹ The FDA noted that the products were not withdrawn for reasons of safety or effectiveness.³²²¹; ³⁷⁸¹

pH

Reconstituted solution using the formulation with arginine, histidine, and isoleucine (Hikma): 5.7 to 6.7.³⁴³¹

Trade Name(s)

Cubicin

Daptomycin is administered by intravenous injection (only in adult patients) or by intravenous infusion (in adult and pediatric patients).³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸² Frozen premixed infusion solutions, after thawing, are intended for intravenous infusion only.³⁴³²

For intravenous injection in adult patients only, the appropriate volume of the reconstituted solution should be withdrawn from the vial using a syringe with a beveled, 21-gauge or smaller needle and may be administered without further dilution over 2 minutes.³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸² The drug should not be administered to pediatric patients by direct intravenous injection.³²²²; ³⁴³¹; ³⁷⁸²

For intravenous infusion, withdraw the appropriate volume of reconstituted solution from the vial using a beveled, 21-gauge or smaller needle and transfer to an infusion bag containing 50 mL sodium chloride 0.9% for adults and children 7 years of age or older, or 25 mL sodium chloride 0.9% for children 1 to 6 years of age.³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸²

Diluted solutions should be infused over 30 minutes in adults and children 7 years of age or older (i.e., 1.67 mL/minute) or over 60 minutes in children 1 to 6 years of age (i.e., 0.42 mL/minute).³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸²

Frozen premixed solutions, after thawing, should be infused over 30 minutes in adults and children 7 years of age or older (i.e., 1.67 mL/min for a 50-mL container or 3.33 mL/min for a 100-mL container) or over 60 minutes in children 1 to 6 years of age (i.e., 0.83 mL/min for a 50-mL container or 1.67 mL/min for a 100-mL container).³⁴³²

Product labeling for some formulations also state that daptomycin is also compatible with Ringer's injection, lactated; consult specific product labeling for additional information.³⁷⁸⁰; ³⁷⁸²

If a common infusion line is being used to administer other drugs, the line should be flushed with a compatible infusion solution prior to and following infusion of daptomycin.³²²²; ³⁴³¹; ³⁴³²; ³⁷⁸⁰; ³⁷⁸²

Daptomycin is a pale yellow to light brown powder or cake that forms a pale yellow to light brown solution upon reconstitution.³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸² Frozen premixed infusion solutions, after thawing, should be a clear, slightly yellow solution.³⁴³² Any unused portion in single-dose vials or plastic containers should be discarded.³²²²; ³⁴³¹; ³⁴³²; ³⁷⁸⁰; ³⁷⁸²

Daptomycin formulations differ in storage requirements and stability following reconstitution or dilution.³²²²; ³⁴³¹; ³⁷⁸⁰ Specific product labeling should be consulted for additional details.³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸²

Intact vials of some daptomycin formulations with sodium hydroxide to be reconstituted with sodium chloride 0.9% (Cubicin, Merck; generic) should be stored at 2 to 8°C.³²²²; ³⁷⁸² Although refrigerated storage is required, one manufacturer has stated that the drug may be stored at room temperature for 12 months.²⁷⁴⁵ Exposure to excessive heat should be avoided.³²²²; ³⁷⁸² When reconstituted as directed, these formulations of daptomycin are stated to be stable in the vial for 12 hours at room temperature or up to 48 hours at 2 to 8°C; if diluted for infusion, the solutions are stable in the infusion bag for 12 hours at room temperature or up to 48 hours at 2 to 8°C.³²²²; ³⁷⁸² However, the time after reconstitution in the vial and after dilution for infusion in the bag should not exceed a combined time of 12 hours at room temperature or 48 hours at 2 to 8°C for these formulations.³²²²; ³⁷⁸²

Another manufacturer of daptomycin with sodium hydroxide and citric acid to be reconstituted with sodium chloride 0.9% (Hospira) states that intact vials may be stored at 2 to 8°C or at controlled room temperature.³⁷⁸⁰ Reconstituted solutions of this formulation are stable in the vial for 12 hours at room temperature under normal light conditions or up to 48 hours at 2 to 8°C and protected from light.³⁷⁸⁰ If diluted in Ringer's injection, lactated, solutions for infusion using this formulation are stable for 12 hours at room temperature under normal light conditions or up to 48 hours at 2 to 8°C and protected from light; the combined storage time after reconstitution in the vial and dilution in the infusion bag should not exceed a combined time of 12 hours at room temperature or 48 hours at 2 to 8°C.³⁷⁸⁰ If diluted in sodium chloride 0.9%, solutions for infusion using this formulation are stable for 12 hours at room temperature under normal light conditions or 10 days at 2 to 8°C and protected from light; the combined storage time after reconstitution in the vial and dilution in the infusion bag should not exceed 12 hours at room temperature or 10 days at 2 to 8°C.³⁷⁸⁰

The formulation with arginine, histidine, and isoleucine (Hikma) should be stored at controlled room temperature prior to use.³⁴³¹ The in-use time for reconstituted solutions depends on the diluent used.³⁴³¹ When reconstituted with sterile water for injection, the in-use shelf life is stated to be 1 day at room temperature or 3 days refrigerated.³⁴³¹ When reconstituted with bacteriostatic water for injection, the in-use shelf life is stated to be 2 days at room temperature or 3 days refrigerated.³⁴³¹ For diluted solutions for infusion, if originally reconstituted with sterile water for injection and immediately diluted in sodium chloride 0.9%, the in-use shelf life is stated to be 19 hours at room temperature or 3 days refrigerated.³⁴³¹ If originally reconstituted with bacteriostatic water for injection and immediately diluted in sodium chloride 0.9%, the in-use shelf life is stated to be 2 days at room temperature or 5 days refrigerated.³⁴³¹

Daptomycin is not compatible in dextrose-containing solutions.³²²²; ³⁷⁸⁰; ³⁷⁸² (See Additional Compatibility Information: Peritoneal Dialysis Solutions.)

Freezing Solutions

Frozen premixed infusion solutions in single-dose Galaxy plastic containers should be stored at -20°C.³⁴³² Solutions should be thawed at room temperature or under refrigeration; do not force thaw or thaw by immersion in water baths or by microwave irradiation.³⁴³² Thawed solutions are stable for 48 hours at room temperature or 30 days refrigerated.³⁴³² Do not refreeze after thawing.³⁴³² The container should be agitated after reaching room temperature.³⁴³² Thawed solutions should be clear and slightly yellow in color; discard the solution if it is cloudy or precipitate is present.³⁴³²

Syringes

The in-use shelf life of the formulation with arginine, histidine, and isoleucine (Hikma) in polypropylene syringes with elastomeric plunger stopper, if reconstituted with sterile water for injection, is stated to be 1 day at room temperature or 3 days refrigerated.³⁴³¹ If reconstituted with bacteriostatic water for injection, the in-use shelf life of this formulation in polypropylene syringes is stated to be 2 days at room temperature or 5 days refrigerated.³⁴³¹

Ambulatory Pumps

During stability studies of daptomycin stored in ReadyMed elastomeric infusion pumps, an impurity (i.e., 2-mercaptobenzothiazole) was found to leach from the pump system into the daptomycin solution.³²²² Therefore, manufacturers state that the drug should not be used in conjunction with ReadyMed elastomeric infusion pumps.³²²²; ³⁴³¹; ³⁷⁸⁰; ³⁷⁸²

Filtration

A study was performed on the compatibility of various syringe filters with the Cubicin (Cubist) formulation of daptomycin after reconstitution of each vial with 10 mL of sodium chloride 0.9%.³¹⁹⁸; ³¹⁹⁹ Visual assessment and potency of the filtered solution were compared with those of the unfiltered control.³¹⁹⁸; ³¹⁹⁹ No changes in color or clarity occurred.³¹⁹⁸; ³¹⁹⁹ Decreases in potency of the reconstituted and filtered solutions compared with the reconstituted and unfiltered solutions ranged from 0.39 to 2.23%.³¹⁹⁸; ³¹⁹⁹ The syringe filters noted in Table 1 were found to be compatible with the reconstituted drug.³¹⁹⁸; ³¹⁹⁹

Table 1. Syringe Filters Compatible with Reconstituted Cubicin³¹⁹⁸; ³¹⁹⁹

Solution Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

Additional Compatibility Information

Peritoneal Dialysis Solutions

Daptomycin (Cubicin, Novartis) 20 mg/L was physically compatible with both Physioneal 35 with dextrose 1.36% (Baxter) and Physioneal 35 with dextrose 2.27% (Baxter) peritoneal dialysis solutions at 25°C for up to 24 hours in polyvinyl chloride (PVC) containers.²⁹⁷⁹ Daptomycin also was physically compatible with both of these solutions at 37°C for up to 6 hours in PVC containers.²⁹⁷⁹

Daptomycin (Cubicin, MSD) also was physically compatible with an icodextrin-based peritoneal dialysis solution in dual-chamber polypropylene bags (Nicopeliq, Terumo).³⁰¹⁰ Following reconstitution with saline, 350 mg of daptomycin was added to the large chamber resulting in an approximate concentration of 278 mg/L.³⁰¹⁰ Daptomycin was stable for up to 72 hours at room temperature, protected from light, or up to 12 hours at 37°C protected from light.³⁰¹⁰

Daptomycin (Cubicin, Cubist) 50 mg/L, 100 mg/L, and 200 mg/L was physically compatible with Physioneal 40 with 1.36% dextrose (Baxter) and Nutrineal (Baxter) at 4, 25, and 37°C in PVC and glass containers for at least 24 hours.²⁹⁸⁰

Daptomycin (Cubicin, MSD) was physically compatible the following peritoneal dialysis solutions: Dianeal low calcium with 2.5% dextrose in UltraBag (Baxter), Extraneal icodextrin 7.5% in UltraBag (Baxter), or Stay Safe Balance with 2.3% glucose (Fresenius).³⁴³³ At a concentration of 70 mg/L, daptomycin was stable in Dianeal low calcium with 2.5% dextrose for 48 hours and in Extraneal icodextrin 7.5% or Stay Safe Balance with 2.3% glucose for up to 24 hours at 25°C.³⁴³³ At a concentration of 245 mg/L, daptomycin was stable in Dianeal low calcium with 2.5% dextrose and Stay Safe Balance with 2.3% glucose for up to 12 hours and in Extraneal with icodextrin 7.5% for up to 48 hours at 25°C.³⁴³³

Heparin Locks

A combination of daptomycin (Cubicin, Cubist) 5 mg/mL and heparin sodium (Hospira) 100 units/mL in Ringer’s injection, lactated was evaluated for stability as a lock solution stored in 5-mL aliquots in 5-mL polypropylene syringes (Becton Dickinson) at 4 and -20°C.²⁹⁷⁸ The solution remained clear and colorless on visual inspection and little or no loss of either drug occurred throughout the 14-day study period.²⁹⁷⁸

For a list of references cited in the text of this monograph, search the monograph titled References.

ASHP^® Injectable Drug Information^TM. Selected Revisions September 30, 2026. © Copyright, 2026. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.