Daptomycin
Daptomycin Prescribing Information
Daptomycin for injection is a lipopeptide antibacterial indicated for the treatment of:
- Complicated skin and skin structure infections (cSSSI) in adult and pediatric patients (1 to 17 years of age) () and,
1.1 Complicated Skin and Skin Structure Infections (cSSSI)Daptomycin for injection is indicated for the treatment of adult and pediatric patients (1 to 17 years of age) with complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive bacteria:
Staphylococcus aureus(including methicillin-resistant isolates),Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis, and Enterococcus faecalis(vancomycin-susceptible isolates only). - Staphylococcus aureusbloodstream infections (bacteremia), in adult patients including those with right-sided infective endocarditis, ()
1.2Staphylococcus aureusBloodstream Infections (Bacteremia) in Adult Patients, Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant IsolatesDaptomycin for injection is indicated for the treatment of adult patients with
Staphylococcus aureusbloodstream infections (bacteremia), including adult patients with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates. - Staphylococcus aureusbloodstream infections (bacteremia) in pediatric patients (1 to 17 years of age). ()
1.3Staphylococcus aureusBloodstream Infections (Bacteremia) in Pediatric Patients (1 to 17 Years of Age)Daptomycin for injection is indicated for the treatment of pediatric patients (1 to 17 years of age) with
Staphylococcus aureusbloodstream infections (bacteremia).
- Daptomycin for injection is not indicated for the treatment of pneumonia. ()
1.4 Limitations of UseDaptomycin for injection is not indicated for the treatment of pneumonia.
Daptomycin for injection is not indicated for the treatment of left-sided infective endocarditis due to
S. aureus. The clinical trial of daptomycin for injection in adult patients withS. aureusbloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor[see Clinical Studies (14.2)].Daptomycin for injection has not been studied in patients with prosthetic valve endocarditis.Daptomycin for injection is not recommended in pediatric patients younger than 1 year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs
[see Warnings and Precautions (5.7)and Nonclinical Toxicology (13.2)]. - Daptomycin for injection is not indicated for the treatment of left-sided infective endocarditis due to S. aureus. ()
1.4 Limitations of UseDaptomycin for injection is not indicated for the treatment of pneumonia.
Daptomycin for injection is not indicated for the treatment of left-sided infective endocarditis due to
S. aureus. The clinical trial of daptomycin for injection in adult patients withS. aureusbloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor[see Clinical Studies (14.2)].Daptomycin for injection has not been studied in patients with prosthetic valve endocarditis.Daptomycin for injection is not recommended in pediatric patients younger than 1 year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs
[see Warnings and Precautions (5.7)and Nonclinical Toxicology (13.2)]. - Daptomycin for injection is not recommended in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs. ()
1.4 Limitations of UseDaptomycin for injection is not indicated for the treatment of pneumonia.
Daptomycin for injection is not indicated for the treatment of left-sided infective endocarditis due to
S. aureus. The clinical trial of daptomycin for injection in adult patients withS. aureusbloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor[see Clinical Studies (14.2)].Daptomycin for injection has not been studied in patients with prosthetic valve endocarditis.Daptomycin for injection is not recommended in pediatric patients younger than 1 year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs
[see Warnings and Precautions (5.7)and Nonclinical Toxicology (13.2)].
To reduce the development of drug-resistant bacteria and maintain the effectiveness of daptomycin for injection and other antibacterial drugs, daptomycin for injection should be used to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. (
Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to daptomycin.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of daptomycin for injection and other antibacterial drugs, daptomycin for injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information is available, it should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Empiric therapy may be initiated while awaiting test results.
- Administer to adult patientsintravenously either by injection over a 2-minute period or by infusion over a 30-minute period. (,
2.1 Important Administration Duration InstructionsAdultsAdminister the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL)
to adult patientsintravenously either by injection over a two (2) minute period or by intravenous infusion over a thirty (30) minute period[see Dosage and Administration (2.2, 2.4, 2.7)].Pediatric Patients (1 to 17 Years of Age)Unlike in adults, do NOT administer daptomycin for injection by injection over a two (2) minute period to pediatric patients.- Pediatric Patients 7 to 17 years of Age: Administer daptomycin for injection intravenously by infusion over a 30-minute period[see Dosage and Administration (2.3, 2.5, 2.7)].
- Pediatric Patients 1 to 6 years of Age:Administer daptomycin for injection intravenously by infusion over a 60-minute period[see Dosage and Administration (2.3, 2.5, 2.7)].
)2.7 Preparation and Administration of Daptomycin for InjectionThere are other formulations of daptomycin that have differences concerning reconstitution and storage. Carefully follow the reconstitution and storage procedures described in this labeling.Reconstitution of Daptomycin for Injection VialDaptomycin for injection is supplied in single-dose vials, each containing 500 mg daptomycin as a sterile, lyophilized powder. The contents of a daptomycin for injection vial should be reconstituted with 0.9% sodium chloride injection, using aseptic technique, to 50 mg/mL as follows:
- To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.
- Remove the polypropylene flip-off cap from the daptomycin for injection vial to expose the central portion of the rubber stopper.
- Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface.
- Slowly transfer 10 mL of 0.9% sodium chloride injection through the center of the rubber stopper into the daptomycin for injection vial, pointing the transfer needle toward the wall of the vial. It is recommended that a beveled sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device is used, pointing the transfer needle toward the wall of the vial.
- Ensure that all of the daptomycin for injection powder is wetted by gently rotating the vial.
- Allow the wetted product to stand undisturbed for 10 minutes.
- Gently rotate or swirl the vial contents for a few minutes, as needed, to obtain a completely reconstituted solution.
Administration InstructionsParenteral drug products should be inspected visually for particulate matter prior to administration.
Slowly remove reconstituted liquid (50 mg daptomycin/mL) from the vial using a beveled sterile needle that is 21 gauge or smaller in diameter. Administer as an intravenous injection or infusion as described below:
AdultsIntravenous Injection over a period of 2 minutes- For intravenous (IV) injection over a period of 2 minutes in adult patientsonly: Administer the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL).
Intravenous Infusion over a period of 30 minutes- For IV infusion over a period of 30 minutes in adult patients: The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection.
Pediatric Patients (1 to 17 Years of Age)Intravenous Infusion over a period of 30 or 60 minutes- Unlike in Adults, do NOT administer daptomycin for injection by injection over a two (2) minute period to pediatric patients[see Dosage and Administration (2.1)].
- For Intravenous infusion over a period of 60 minutes in pediatric patients 1 to 6 years of age:The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into an intravenous infusion bag containing 25 mL of 0.9% sodium chloride injection. The infusion rate should be maintained at 0.42 mL/minute over the 60-minute period.
- For Intravenous infusion over a period of 30 minutes in pediatric patients 7 to 17 years of age: The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection. The infusion rate should be maintained at 1.67 mL/minute over the 30-minute period.
No preservative or bacteriostatic agent is present in this product. Aseptic technique must be used in the preparation of final IV solution. Do not exceed the In-Use storage conditions of the reconstituted and diluted solutions of daptomycin for injection described below. Discard unused portions of daptomycin for injection.
In-Use Storage Conditions for Daptomycin for Injection Once Reconstituted in Acceptable Intravenous DiluentsStability studies have shown that the reconstituted solution is stable in the vial for 12 hours at room temperature and up to 48 hours if stored under refrigeration at 2°C to 8°C (36 to 46°F).
The diluted solution is stable in the infusion bag for 12 hours at room temperature and 48 hours if stored under refrigeration. The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration.
- Recommended dosage regimen for adult patients (,
2.2 Dosage in Adults for cSSSIAdminister daptomycin for injection 4 mg/kg to adult patients intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days.
,2.4 Dosage in Adult Patients withStaphylococcus aureusBloodstream Infections (Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant IsolatesAdminister daptomycin for injection 6 mg/kg to adult patients intravenously in 0.9% sodium chloride injection once every 24 hours for 2 to 6 weeks. There are limited safety data for the use of daptomycin for injection for more than 28 days of therapy. In the Phase 3 trial, there were a total of 14 adult patients who were treated with daptomycin for injection for more than 28 days.
):2.6 Dosage in Patients with Renal ImpairmentAdult Patients:No dosage adjustment is required in adult patients with creatinine clearance (CLCR) greater than or equal to 30 mL/min. The recommended dosage regimen for daptomycin for injection in adult patients with CLCRless than 30 mL/min, including adult patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), is 4 mg/kg (cSSSI) or 6 mg/kg (
S. aureusbloodstream infections) once every 48 hours (Table 3). When possible, daptomycin for injection should be administered following the completion of hemodialysis, on hemodialysis days[see Warnings and Precautions (5.2, 5.10), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].Table 3: Recommended Dosage of Daptomycin for Injection in Adult Patients Creatinine Clearance
(CLCR)Dosage Regimen in Adults cSSSI S. aureusBloodstream InfectionsGreater than or equal to 30 mL/min 4 mg/kg once every 24 hours 6 mg/kg once every 24 hours Less than 30 mL/min, including hemodialysis and CAPD 4 mg/kg once every 48 hoursWhen possible, administer daptomycin for injection following the completion of hemodialysis, on hemodialysis days. 6 mg/kg once every 48 hours Pediatric Patients:The dosage regimen for daptomycin for injection in pediatric patients with renal impairment has not been established.
| Creatinine Clearance (CLCR) | Dosage Regimen | |
|---|---|---|
cSSSI For 7 to 14 days | S. aureus Bacteremia For 2 to 6 weeks | |
| ≥30 mL/min | 4 mg/kg once every 24 hours | 6 mg/kg once every 24 hours |
| <30 mL/min, including hemodialysis and CAPD | 4 mg/kg once every 48 hoursAdministered following hemodialysis on hemodialysis days. | 6 mg/kg once every 48 hours |
- Unlike in adults, do NOT administer by injection over a two (2) minute period to pediatric patients. (,
2.1 Important Administration Duration InstructionsAdultsAdminister the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL)
to adult patientsintravenously either by injection over a two (2) minute period or by intravenous infusion over a thirty (30) minute period[see Dosage and Administration (2.2, 2.4, 2.7)].Pediatric Patients (1 to 17 Years of Age)Unlike in adults, do NOT administer daptomycin for injection by injection over a two (2) minute period to pediatric patients.- Pediatric Patients 7 to 17 years of Age: Administer daptomycin for injection intravenously by infusion over a 30-minute period[see Dosage and Administration (2.3, 2.5, 2.7)].
- Pediatric Patients 1 to 6 years of Age:Administer daptomycin for injection intravenously by infusion over a 60-minute period[see Dosage and Administration (2.3, 2.5, 2.7)].
)2.7 Preparation and Administration of Daptomycin for InjectionThere are other formulations of daptomycin that have differences concerning reconstitution and storage. Carefully follow the reconstitution and storage procedures described in this labeling.Reconstitution of Daptomycin for Injection VialDaptomycin for injection is supplied in single-dose vials, each containing 500 mg daptomycin as a sterile, lyophilized powder. The contents of a daptomycin for injection vial should be reconstituted with 0.9% sodium chloride injection, using aseptic technique, to 50 mg/mL as follows:
- To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.
- Remove the polypropylene flip-off cap from the daptomycin for injection vial to expose the central portion of the rubber stopper.
- Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface.
- Slowly transfer 10 mL of 0.9% sodium chloride injection through the center of the rubber stopper into the daptomycin for injection vial, pointing the transfer needle toward the wall of the vial. It is recommended that a beveled sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device is used, pointing the transfer needle toward the wall of the vial.
- Ensure that all of the daptomycin for injection powder is wetted by gently rotating the vial.
- Allow the wetted product to stand undisturbed for 10 minutes.
- Gently rotate or swirl the vial contents for a few minutes, as needed, to obtain a completely reconstituted solution.
Administration InstructionsParenteral drug products should be inspected visually for particulate matter prior to administration.
Slowly remove reconstituted liquid (50 mg daptomycin/mL) from the vial using a beveled sterile needle that is 21 gauge or smaller in diameter. Administer as an intravenous injection or infusion as described below:
AdultsIntravenous Injection over a period of 2 minutes- For intravenous (IV) injection over a period of 2 minutes in adult patientsonly: Administer the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL).
Intravenous Infusion over a period of 30 minutes- For IV infusion over a period of 30 minutes in adult patients: The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection.
Pediatric Patients (1 to 17 Years of Age)Intravenous Infusion over a period of 30 or 60 minutes- Unlike in Adults, do NOT administer daptomycin for injection by injection over a two (2) minute period to pediatric patients[see Dosage and Administration (2.1)].
- For Intravenous infusion over a period of 60 minutes in pediatric patients 1 to 6 years of age:The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into an intravenous infusion bag containing 25 mL of 0.9% sodium chloride injection. The infusion rate should be maintained at 0.42 mL/minute over the 60-minute period.
- For Intravenous infusion over a period of 30 minutes in pediatric patients 7 to 17 years of age: The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection. The infusion rate should be maintained at 1.67 mL/minute over the 30-minute period.
No preservative or bacteriostatic agent is present in this product. Aseptic technique must be used in the preparation of final IV solution. Do not exceed the In-Use storage conditions of the reconstituted and diluted solutions of daptomycin for injection described below. Discard unused portions of daptomycin for injection.
In-Use Storage Conditions for Daptomycin for Injection Once Reconstituted in Acceptable Intravenous DiluentsStability studies have shown that the reconstituted solution is stable in the vial for 12 hours at room temperature and up to 48 hours if stored under refrigeration at 2°C to 8°C (36 to 46°F).
The diluted solution is stable in the infusion bag for 12 hours at room temperature and 48 hours if stored under refrigeration. The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration.
- Administer to pediatric patientsintravenously by infusion over a 30- or 60-minute period, based on age. (,
2.1 Important Administration Duration InstructionsAdultsAdminister the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL)
to adult patientsintravenously either by injection over a two (2) minute period or by intravenous infusion over a thirty (30) minute period[see Dosage and Administration (2.2, 2.4, 2.7)].Pediatric Patients (1 to 17 Years of Age)Unlike in adults, do NOT administer daptomycin for injection by injection over a two (2) minute period to pediatric patients.- Pediatric Patients 7 to 17 years of Age: Administer daptomycin for injection intravenously by infusion over a 30-minute period[see Dosage and Administration (2.3, 2.5, 2.7)].
- Pediatric Patients 1 to 6 years of Age:Administer daptomycin for injection intravenously by infusion over a 60-minute period[see Dosage and Administration (2.3, 2.5, 2.7)].
)2.7 Preparation and Administration of Daptomycin for InjectionThere are other formulations of daptomycin that have differences concerning reconstitution and storage. Carefully follow the reconstitution and storage procedures described in this labeling.Reconstitution of Daptomycin for Injection VialDaptomycin for injection is supplied in single-dose vials, each containing 500 mg daptomycin as a sterile, lyophilized powder. The contents of a daptomycin for injection vial should be reconstituted with 0.9% sodium chloride injection, using aseptic technique, to 50 mg/mL as follows:
- To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.
- Remove the polypropylene flip-off cap from the daptomycin for injection vial to expose the central portion of the rubber stopper.
- Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface.
- Slowly transfer 10 mL of 0.9% sodium chloride injection through the center of the rubber stopper into the daptomycin for injection vial, pointing the transfer needle toward the wall of the vial. It is recommended that a beveled sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device is used, pointing the transfer needle toward the wall of the vial.
- Ensure that all of the daptomycin for injection powder is wetted by gently rotating the vial.
- Allow the wetted product to stand undisturbed for 10 minutes.
- Gently rotate or swirl the vial contents for a few minutes, as needed, to obtain a completely reconstituted solution.
Administration InstructionsParenteral drug products should be inspected visually for particulate matter prior to administration.
Slowly remove reconstituted liquid (50 mg daptomycin/mL) from the vial using a beveled sterile needle that is 21 gauge or smaller in diameter. Administer as an intravenous injection or infusion as described below:
AdultsIntravenous Injection over a period of 2 minutes- For intravenous (IV) injection over a period of 2 minutes in adult patientsonly: Administer the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL).
Intravenous Infusion over a period of 30 minutes- For IV infusion over a period of 30 minutes in adult patients: The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection.
Pediatric Patients (1 to 17 Years of Age)Intravenous Infusion over a period of 30 or 60 minutes- Unlike in Adults, do NOT administer daptomycin for injection by injection over a two (2) minute period to pediatric patients[see Dosage and Administration (2.1)].
- For Intravenous infusion over a period of 60 minutes in pediatric patients 1 to 6 years of age:The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into an intravenous infusion bag containing 25 mL of 0.9% sodium chloride injection. The infusion rate should be maintained at 0.42 mL/minute over the 60-minute period.
- For Intravenous infusion over a period of 30 minutes in pediatric patients 7 to 17 years of age: The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection. The infusion rate should be maintained at 1.67 mL/minute over the 30-minute period.
No preservative or bacteriostatic agent is present in this product. Aseptic technique must be used in the preparation of final IV solution. Do not exceed the In-Use storage conditions of the reconstituted and diluted solutions of daptomycin for injection described below. Discard unused portions of daptomycin for injection.
In-Use Storage Conditions for Daptomycin for Injection Once Reconstituted in Acceptable Intravenous DiluentsStability studies have shown that the reconstituted solution is stable in the vial for 12 hours at room temperature and up to 48 hours if stored under refrigeration at 2°C to 8°C (36 to 46°F).
The diluted solution is stable in the infusion bag for 12 hours at room temperature and 48 hours if stored under refrigeration. The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration.
- Recommended dosage regimen for pediatric patients (1 to 17 years of age) with cSSSI, based on age ():
2.3 Dosage in Pediatric Patients (1 to 17 Years of Age) for cSSSIThe recommended dosage regimens based on age for pediatric patients with cSSSI are shown in Table 1. Administer daptomycin for injection intravenously in 0.9% sodium chloride injection once every 24 hours for up to 14 days.
Table 1: Recommended Dosage of Daptomycin for Injection in Pediatric Patients (1 to 17 Years of Age) with cSSSI, Based on Age Age Range Dosage RegimenRecommended dosage regimen is for pediatric patients (1 to 17 years of age) with normal renal function. Dosage adjustment for pediatric patients with renal impairment has not been established. Duration of therapy 12 to 17 years 5 mg/kg once every 24 hours infused over 30 minutes 7 to 11 years 7 mg/kg once every 24 hours infused over 30 minutes 2 to 6 years 9 mg/kg once every 24 hours infused over 60 minutes Up to 14 days 1 to less than 2 years 10 mg/kg once every 24 hours infused over 60 minutes
| Age group | DosageRecommended dosage is for pediatric patients (1 to 17 years of age) with normal renal function. Dosage adjustment for pediatric patients with renal impairment has not been established. | Duration of therapy |
|---|---|---|
| 12 to 17 years | 5 mg/kg once every 24 hours infused over 30 minutes | Up to 14 days |
| 7 to 11 years | 7 mg/kg once every 24 hours infused over 30 minutes | |
| 2 to 6 years | 9 mg/kg once every 24 hours infused over 60 minutes | |
| 1 to less than 2 years | 10 mg/kg once every 24 hours infused over 60 minutes |
- Recommended dosage regimen for pediatric patients (1 to 17 years of age) with S. aureusbacteremia, based on age ():
2.5 Dosage in Pediatric Patients (1 to 17 Years of Age) withStaphylococcus aureusBloodstream Infections (Bacteremia)The recommended dosage regimens based on age for pediatric patients with
S. aureusbloodstream infections (bacteremia) are shown in Table 2. Administer daptomycin for injection intravenously in 0.9% sodium chloride injection once every 24 hours for up to 42 days.Table 2: Recommended Dosage of Daptomycin for Injection in Pediatric Patients (1 to 17 Years of Age) with S. aureus Bacteremia, Based on Age Age group DosageRecommended dosage is for pediatric patients (1 to 17 years of age) with normal renal function. Dosage adjustment for pediatric patients with renal impairment has not been established. Duration of therapy 12 to 17 years 7 mg/kg once every 24 hours infused over 30 minutes 7 to 11 years 9 mg/kg once every 24 hours infused over 30 minutes Up to 42 days 1 to 6 years 12 mg/kg once every 24 hours infused over 60 minutes
| Age group | DosageRecommended dosage is for pediatric patients (1 to 17 years of age) with normal renal function. Dosage adjustment for pediatric patients with renal impairment has not been established. | Duration of therapy |
|---|---|---|
| 12 to 17 years | 7 mg/kg once every 24 hours infused over 30 minutes | Up to 42 days |
| 7 to 11 years | 9 mg/kg once every 24 hours infused over 30 minutes | |
| 1 to 6 years | 12 mg/kg once every 24 hours infused over 60 minutes |
- There are two formulations of daptomycin that have differences concerning storage and reconstitution. Carefully follow the reconstitution and storage procedures in labeling. ()
2.7 Preparation and Administration of Daptomycin for InjectionThere are other formulations of daptomycin that have differences concerning reconstitution and storage. Carefully follow the reconstitution and storage procedures described in this labeling.Reconstitution of Daptomycin for Injection VialDaptomycin for injection is supplied in single-dose vials, each containing 500 mg daptomycin as a sterile, lyophilized powder. The contents of a daptomycin for injection vial should be reconstituted with 0.9% sodium chloride injection, using aseptic technique, to 50 mg/mL as follows:
- To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.
- Remove the polypropylene flip-off cap from the daptomycin for injection vial to expose the central portion of the rubber stopper.
- Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface.
- Slowly transfer 10 mL of 0.9% sodium chloride injection through the center of the rubber stopper into the daptomycin for injection vial, pointing the transfer needle toward the wall of the vial. It is recommended that a beveled sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device is used, pointing the transfer needle toward the wall of the vial.
- Ensure that all of the daptomycin for injection powder is wetted by gently rotating the vial.
- Allow the wetted product to stand undisturbed for 10 minutes.
- Gently rotate or swirl the vial contents for a few minutes, as needed, to obtain a completely reconstituted solution.
Administration InstructionsParenteral drug products should be inspected visually for particulate matter prior to administration.
Slowly remove reconstituted liquid (50 mg daptomycin/mL) from the vial using a beveled sterile needle that is 21 gauge or smaller in diameter. Administer as an intravenous injection or infusion as described below:
AdultsIntravenous Injection over a period of 2 minutes- For intravenous (IV) injection over a period of 2 minutes in adult patientsonly: Administer the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL).
Intravenous Infusion over a period of 30 minutes- For IV infusion over a period of 30 minutes in adult patients: The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection.
Pediatric Patients (1 to 17 Years of Age)Intravenous Infusion over a period of 30 or 60 minutes- Unlike in Adults, do NOT administer daptomycin for injection by injection over a two (2) minute period to pediatric patients[see Dosage and Administration (2.1)].
- For Intravenous infusion over a period of 60 minutes in pediatric patients 1 to 6 years of age:The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into an intravenous infusion bag containing 25 mL of 0.9% sodium chloride injection. The infusion rate should be maintained at 0.42 mL/minute over the 60-minute period.
- For Intravenous infusion over a period of 30 minutes in pediatric patients 7 to 17 years of age: The appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection. The infusion rate should be maintained at 1.67 mL/minute over the 30-minute period.
No preservative or bacteriostatic agent is present in this product. Aseptic technique must be used in the preparation of final IV solution. Do not exceed the In-Use storage conditions of the reconstituted and diluted solutions of daptomycin for injection described below. Discard unused portions of daptomycin for injection.
In-Use Storage Conditions for Daptomycin for Injection Once Reconstituted in Acceptable Intravenous DiluentsStability studies have shown that the reconstituted solution is stable in the vial for 12 hours at room temperature and up to 48 hours if stored under refrigeration at 2°C to 8°C (36 to 46°F).
The diluted solution is stable in the infusion bag for 12 hours at room temperature and 48 hours if stored under refrigeration. The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration.
- Do not use in conjunction with ReadyMED® elastomeric infusion pumps in adult and pediatric patients. ()
2.9 IncompatibilitiesDaptomycin for injection is not compatible with dextrose-containing diluents.
Daptomycin for injection should not be used in conjunction with ReadyMED®elastomeric infusion pumps. Stability studies of daptomycin for injection solutions stored in ReadyMED®elastomeric infusion pumps identified an impurity (2-mercaptobenzothiazole) leaching from this pump system into the daptomycin for injection solution.
Because only limited data are available on the compatibility of daptomycin for injection with other IV substances, additives and other medications should not be added to daptomycin for injection single-dose vials or infusion bags, or infused simultaneously with daptomycin for injection through the same IV line. If the same IV line is used for sequential infusion of different drugs, the line should be flushed with a compatible intravenous solution before and after infusion with daptomycin for injection.
For Injection: 500 mg daptomycin as a sterile, pale yellow to light brown lyophilized powder for reconstitution in a single-dose vial.
Limited published data on use of daptomycin for injection in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies performed in rats and rabbits daptomycin was administered intravenously during organogenesis at doses 2 and 4-times, respectively, the recommended 6 mg/kg human dose (on a body surface area basis). No evidence of adverse developmental outcomes was observed.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Daptomycin for injection is contraindicated in patients with known hypersensitivity to daptomycin
Anaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including daptomycin for injection, and may be life-threatening. If an allergic reaction to daptomycin for injection occurs, discontinue the drug and institute appropriate therapy
- Anaphylaxis/hypersensitivity reactions (including life-threatening): Discontinue daptomycin for injection and treat signs/symptoms. ()
5.1 Anaphylaxis/Hypersensitivity ReactionsAnaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including daptomycin for injection, and may be life-threatening. If an allergic reaction to daptomycin for injection occurs, discontinue the drug and institute appropriate therapy
[see Adverse Reactions (6.2)]. - Myopathy and rhabdomyolysis: Monitor CPK levels and follow muscle pain or weakness; if elevated CPK or myopathy occurs, consider discontinuation of daptomycin for injection. ()
5.2 Myopathy and RhabdomyolysisMyopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper limit of normal (ULN), has been reported with the use of daptomycin for injection. Rhabdomyolysis, with or without acute renal failure, has been reported
[see Adverse Reactions (6.2)].Patients receiving daptomycin for injection should be monitored for the development of muscle pain or weakness, particularly of the distal extremities. In patients who receive daptomycin for injection, CPK levels should be monitored weekly, and more frequently in patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment with daptomycin for injection.
In adult patients with renal impairment, both renal function and CPK should be monitored more frequently than once weekly
[see Use in Specific Populations (8.6)and Clinical Pharmacology (12.3)].In Phase 1 studies and Phase 2 clinical trials in adults, CPK elevations appeared to be more frequent when daptomycin for injection was dosed more than once daily. Therefore, daptomycin for injection should not be dosed more frequently than once a day.
Daptomycin for injection should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to levels >1,000 U/L (~5× ULN), and in patients without reported symptoms who have marked elevations in CPK, with levels >2,000 U/L (≥10× ULN). In addition, consideration should be given to suspending agents associated with rhabdomyolysis, such as HMG-CoA reductase inhibitors, temporarily in patients receiving daptomycin for injection
[see Drug Interactions (7.1)]. - Eosinophilic pneumonia: Discontinue daptomycin for injection and consider treatment with systemic steroids. ()
5.3 Eosinophilic PneumoniaEosinophilic pneumonia has been reported in patients receiving daptomycin for injection
[see Adverse Reactions (6.2)].In reported cases associated with daptomycin for injection, patients developed fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates or organizing pneumonia. In general, patients developed eosinophilic pneumonia 2 to 4 weeks after starting daptomycin for injection and improved when daptomycin for injection was discontinued and steroid therapy was initiated. Recurrence of eosinophilic pneumonia upon re-exposure has been reported. Patients who develop these signs and symptoms while receiving daptomycin for injection should undergo prompt medical evaluation, and daptomycin for injection should be discontinued immediately. Treatment with systemic steroids is recommended. - Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue daptomycin for injection and institute appropriate treatment. ()
5.4 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)DRESS has been reported in post-marketing experience with daptomycin for injection
[see Adverse Reactions (6.2)]. Patients who develop skin rash, fever, peripheral eosinophilia, and systemic organ (for example, hepatic, renal, pulmonary) impairment while receiving daptomycin for injection should undergo medical evaluation. If DRESS is suspected, discontinue daptomycin for injection promptly and institute appropriate treatment. - Tubulointerstitial Nephritis (TIN): Discontinue daptomycin for injection and institute appropriate treatment. ()
5.5 Tubulointerstitial Nephritis (TIN)TIN has been reported in post-marketing experience with daptomycin for injection
[see Adverse Reactions (6.2)]. Patients who develop new or worsening renal impairment while receiving daptomycin for injection should undergo medical evaluation. If TIN is suspected, discontinue daptomycin for injection promptly and institute appropriate treatment. - Peripheral neuropathy: Monitor for neuropathy and consider discontinuation. ()
5.6 Peripheral NeuropathyCases of peripheral neuropathy have been reported during the daptomycin for injection postmarketing experience
[see Adverse Reactions (6.2)].Therefore, physicians should be alert to signs and symptoms of peripheral neuropathy in patients receiving daptomycin for injection. Monitor for neuropathy and consider discontinuation. - Potential nervous system and/or muscular system effects in pediatric patients younger than 12 months: Avoid use of daptomycin for injection in this age group. ()
5.7 Potential Nervous System and/or Muscular System Effects in Pediatric Patients Younger than 12 MonthsAvoid use of daptomycin for injection in pediatric patients younger than 12 months due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs with intravenous daptomycin
[see Nonclinical Toxicology (13.2)]. - Clostridioides difficile–associated diarrhea: Evaluate patients if diarrhea occurs. ()
5.8Clostridioides difficile-Associated DiarrheaClostridioides difficile–associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including daptomycin for injection, and may range in severity from mild diarrhea to fatal colitis[see Adverse Reactions (6.2)].Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth ofC. difficile.C. difficileproduces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains ofC. difficilecause increased morbidity and mortality, since these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.If CDAD is suspected or confirmed, ongoing antibacterial use not directed against
C. difficilemay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment ofC. difficile, and surgical evaluation should be instituted as clinically indicated. - Persisting or relapsing S. aureusbacteremia/endocarditis: Perform susceptibility testing and rule out sequestered foci of infection. ()
5.9 Persisting or RelapsingS. aureusBacteremia/EndocarditisPatients with persisting or relapsing
S. aureusbacteremia/endocarditis or poor clinical response should have repeat blood cultures. If a blood culture is positive forS. aureus, minimum inhibitory concentration (MIC) susceptibility testing of the isolate should be performed using a standardized procedure, and diagnostic evaluation of the patient should be performed to rule out sequestered foci of infection. Appropriate surgical intervention (e.g., debridement, removal of prosthetic devices, valve replacement surgery) and/or consideration of a change in antibacterial regimen may be required.Failure of treatment due to persisting or relapsing
S. aureusbacteremia/endocarditis may be due to reduced daptomycin susceptibility (as evidenced by increasing MIC of theS. aureusisolate)[see Clinical Studies (14.2)]. - Decreased efficacy was observed in adult patients with moderate baseline renal impairment. ()
5.10 Decreased Efficacy in Patients with Moderate Baseline Renal ImpairmentLimited data are available from the two Phase 3 complicated skin and skin structure infection (cSSSI) trials regarding clinical efficacy of daptomycin for injection treatment in adult patients with creatinine clearance (CLCR) <50 mL/min; only 31/534 (6%) patients treated with daptomycin for injection in the intent-to-treat (ITT) population had a baseline CLCR<50 mL/min. Table 4 shows the number of adult patients by renal function and treatment group who were clinical successes in the Phase 3 cSSSI trials.
Table 4: Clinical Success Rates by Renal Function and Treatment Group in Phase 3 cSSSI Trials in Adult Patients (Population: ITT) CLCR Success Rate
n/N (%)Daptomycin for Injection
4 mg/kg every 24hComparator 50-70 mL/min 25/38 (66%) 30/48 (63%) 30-<50 mL/min 7/15 (47%) 20/35 (57%) In a subgroup analysis of the ITT population in the Phase 3
S. aureusbacteremia/endocarditis trial, clinical success rates, as determined by a treatment-blinded Adjudication Committee[see Clinical Studies (14.2)], in the daptomycin for injection-treated adult patients were lower in patients with baseline CLCR<50 mL/min (see Table 5). A decrease of the magnitude shown in Table 5 was not observed in comparator-treated patients.Table 5: Adjudication Committee Clinical Success Rates at Test of Cure by Baseline Creatinine Clearance and Treatment Subgroup in the S. aureus Bacteremia/Endocarditis Trial in Adult Patients (Population: ITT) Baseline CLCR Success Rate
n/N (%)Daptomycin for Injection
6 mg/kg every 24hComparator Bacteremia Right-Sided Infective Endocarditis Bacteremia Right-Sided Infective Endocarditis >80 mL/min 30/50 (60%) 7/14 (50%) 19/42 (45%) 5/11 (46%) 50–80 mL/min 12/26 (46%) 1/4 (25%) 13/31 (42%) 1/2 (50%) 30–<50 mL/min 2/14 (14%) 0/1 (0%) 7/17 (41%) 1/1 (100%) Consider these data when selecting antibacterial therapy for use in adult patients with baseline moderate to severe renal impairment.