AHFS Class:

8:12.28.12 Cyclic Lipopeptides

Daptomycin is available as a lyophilized powder or cake in single-use (preservative-free) vials.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸² Several different formulations of daptomycin are available; the formulations differ in storage requirements, directions for reconstitution and dilution, and stability following reconstitution or dilution.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸² Specific product labeling should be consulted for additional details.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸²

Daptomycin is available in 350- or 500-mg single-use vials with sodium hydroxide to adjust the pH (Cubicin, Merck; generic).²⁹⁷⁷; ³²²²; ³⁷⁸² Some formulations may also contain citric acid 53.8 or 76.8 mg in each 350- or 500-mg single-use vials, respectively (Hospira).³⁷⁸⁰ These products should be reconstituted with sodium chloride 0.9%.²⁹⁷⁷; 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.²⁹⁷⁷; 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.²⁹⁷⁷; ³²²²; ³⁷⁸² The reconstituted vial should be allowed to stand undisturbed for 10 minutes before gently rotating or swirling to ensure complete dissolution.²⁹⁷⁷; ³²²²; ³⁷⁸² Vigorous agitation or shaking of the vial should be avoided to minimize foaming.²⁹⁷⁷; ³²²²; ³⁷⁸⁰; ³⁷⁸² The reconstituted solution has a daptomycin concentration of 50 mg/mL.²⁹⁷⁷; ³²²²; ³⁷⁸⁰; ³⁷⁸²

Daptomycin also is available in certain formulations to be reconstituted with sterile water for injection or bacteriostatic water for injection.³²²¹; ³⁷⁸¹ Daptomycin formulated with sucrose (Cubicin RF, Merck) is available in single-use vials containing daptomycin 500 mg, sucrose 713 mg, and sodium hydroxide to adjust the pH.³²²¹ Daptomycin formulated with sorbitol and mannitol (Dapzura RT, Baxter) is available in single-use vials containing daptomycin 500 mg, sorbitol 238 mg, mannitol 238 mg, and sodium hydroxide and/or hydrochloric acid to adjust the pH.³⁷⁸¹ These products should be reconstituted only with 10 mL of sterile water for injection or bacteriostatic water for injection; a syringe with a beveled, 21-gauge or smaller transfer needle should be used to slowly direct the stream of diluent against the vial wall.³²²¹; ³⁷⁸¹ Saline-based diluents must not be used to reconstitute these formulations because the resulting solution is hyperosmotic and may lead to infusion-site reactions if administered as a direct injection (e.g., over 2 minutes).³²²¹; ³⁷⁸¹ The vial should be rotated or swirled for a few minutes, as needed, to ensure complete dissolution of the powder.³²²¹; ³⁷⁸¹ The reconstituted solution has a daptomycin concentration of 50 mg/mL.³²²¹; ³⁷⁸¹

pH

When reconstituted as directed, the pH of a 50-mg/mL solution of Cubicin RF or Dapzura RT is 6.8.³²²¹; ³⁷⁸¹

Trade Name(s)

Cubicin, Cubicin RF, Dapzura RT

Daptomycin is administered by intravenous injection (only in adult patients) or by intravenous infusion (in adult and pediatric patients).²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸²

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.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸² The drug should not be administered to pediatric patients by direct intravenous injection.²⁹⁷⁷; ³²²¹; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸²

To prepare intravenous infusions of daptomycin, a syringe with a beveled, 21-gauge or smaller needle should be used to withdraw the appropriate volume of reconstituted solution from the vial and transfer the drug to a bag containing the appropriate volume of infusion solution.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸²

For intravenous infusion in adult patients, the appropriate volume of the reconstituted solution should be withdrawn from the vial and transferred to an infusion bag containing 50 mL of sodium chloride 0.9% to be administered over 30 minutes.²⁹⁷⁷; ³²²¹; ³²²² Some formulations also may be diluted in Ringer's injection, lactated; consult specific product labeling for additional information.²⁹⁷⁷; ³²²²; ³⁷⁸⁰; ³⁷⁸²

For intravenous infusion in pediatric patients 1 to 6 years of age, the appropriate volume of the reconstituted solution should be withdrawn from the vial and transferred to an infusion bag containing 25 mL of sodium chloride 0.9%.²⁹⁷⁷; ³²²¹; ³⁷⁸¹ The diluted solution should be administered over 60 minutes; the infusion rate should be maintained at 0.42 mL/min over the 60-minute period of infusion.²⁹⁷⁷; ³²²¹; ³⁷⁸¹ Some formulations also may be diluted in Ringer's injection, lactated; consult specific product labeling for additional information.²⁹⁷⁷; ³²²²

For intravenous infusion in pediatric patients 7 to 17 years of age, the appropriate volume of the reconstituted solution should be withdrawn from the vial and transferred to an infusion bag containing 50 mL of sodium chloride 0.9%.²⁹⁷⁷; ³²²¹; ³⁷⁸¹ The diluted solution should be administered over 30 minutes; the infusion rate should be maintained at 1.67 mL/min over the 30-minute period of infusion.²⁹⁷⁷; ³²²¹; ³⁷⁸¹ Some formulations also may be diluted in Ringer's injection, lactated; consult specific product labeling for additional information.²⁹⁷⁷; ³²²²

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.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸²

Daptomycin is a pale yellow to light brown powder or cake that forms a pale yellow to light brown solution upon reconstitution.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸² Vials of daptomycin are for single use only; any unused portion should be discarded.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸²

Daptomycin formulations differ in storage requirements and stability following reconstitution or dilution.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹ Specific product labeling should be consulted for additional details.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸²

Intact vials of certain daptomycin formulations to be reconstituted with sodium chloride 0.9% (Cubicin, Merck; generic) should be stored at 2 to 8°C.²⁹⁷⁷; 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.²⁹⁷⁷; ³²²²; ³⁷⁸² When reconstituted as directed, these formulations of daptomycin are 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.²⁹⁷⁷; 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.²⁹⁷⁷; ³²²²; ³⁷⁸²

Another manufacturer of daptomycin 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

Intact vials of the Cubicin RF (Merck) formulation of daptomycin should be stored at controlled room temperature.³²²¹ When reconstituted as directed with sterile water for injection, Cubicin RF is stable in the vial for 1 day at room temperature or 3 days at 2 to 8°C; if diluted in sodium chloride 0.9% immediately following reconstitution, the drug is stable in the infusion bag for 19 hours at room temperature or 3 days at 2 to 8°C.³²²¹ When reconstituted as directed with bacteriostatic water for injection, Cubicin RF is stable in the vial for 2 days at room temperature or 3 days at 2 to 8°C; if diluted in sodium chloride 0.9% immediately following reconstitution, the drug is stable in the infusion bag for 2 days at room temperature or 5 days at 2 to 8°C.³²²¹

Intact vials of the Dapzura RT (Baxter) formulation of daptomycin should be stored at controlled room temperature.³⁷⁸¹ When reconstituted as directed with sterile water for injection, Dapzura RT is stable in the vial for 18 hours at room temperature or 3 days at 2 to 8°C; if diluted in sodium chloride 0.9% immediately following reconstitution, the drug is stable in the infusion bag for 1 day at room temperature or 3 days at 2 to 8°C.³⁷⁸¹ When reconstituted as directed with bacteriostatic water for injection, Dapzura RF is stable in the vial for 2 days at room temperature or 5 days at 2 to 8°C; if diluted in sodium chloride 0.9% immediately following reconstitution, the drug is stable in the infusion bag for 2 days at room temperature or 5 days at 2 to 8°C.³⁷⁸¹

Daptomycin is not compatible in dextrose-containing solutions.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; ³⁷⁸² (See Additional Compatibility Information: Peritoneal Dialysis Solutions.)

Syringes

The Cubicin RF formulation of daptomycin reconstituted with sterile water for injection to yield a concentration of 50 mg/mL and packaged in polypropylene syringes with an elastomeric plunger stopper is stable for 1 day at room temperature or 3 days at 2 to 8°C; when similarly reconstituted with bacteriostatic water for injection, the drug is stable for 2 days at room temperature or 5 days at 2 to 8°C.³²²¹

The Dapzura RT formulation of daptomycin reconstituted with sterile water for injection to yield a concentration of 50 mg/mL and packaged in polypropylene syringes with an elastomeric plunger stopper is stable for 18 hours at room temperature or 3 days at 2 to 8°C; when similarly reconstituted with bacteriostatic water for injection, the drug is stable for 2 days at room temperature or 5 days at 2 to 8°C.³⁷⁸¹

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.²⁹⁷⁷; ³²²¹; ³²²² Therefore, manufacturers state that the drug should not be used in conjunction with ReadyMed elastomeric infusion pumps.²⁹⁷⁷; ³²²¹; ³²²²; ³⁷⁸⁰; ³⁷⁸¹; 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, 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

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 December 5, 2024. © Copyright, 2024. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.