DAPTOMYCIN: Package Insert and Label Information

DAPTOMYCIN — daptomycin injection, powder, lyophilized, for solution
AuroMedics Pharma LLC

1 INDICATIONS AND USAGE

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).

1.2 Staphylococcus aureus Bloodstream Infections (Bacteremia) in Adult Patients, Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates

Daptomycin for injection is indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia), including adult patients with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates.

1.3 Staphylococcus aureus Bloodstream 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 aureus bloodstream infections (bacteremia).

1.4 Limitations of Use

Daptomycin 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 with S. aureus bloodstream 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)].

1.5 Usage

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.

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Duration Instructions

Adults

Administer the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL) to adult patients intravenously 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.


2.2 Dosage in Adults for cSSSI

Administer 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.

2.3 Dosage in Pediatric Patients (1 to 17 Years of Age) for cSSSI

The 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 Regimen* 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 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.

2.4 Dosage in Adult Patients with Staphylococcus aureus Bloodstream Infections (Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates

Administer 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.

2.5 Dosage in Pediatric Patients (1 to 17 Years of Age) with Staphylococcus aureus Bloodstream Infections (Bacteremia)

The recommended dosage regimens based on age for pediatric patients with S. aureus bloodstream 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 Dosage* 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
*Recommended 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.

2.6 Dosage in Patients with Renal Impairment

Adult 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 CLCR less 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. aureus bloodstream 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
* When possible, administer daptomycin for injection following the completion of hemodialysis, on hemodialysis days.
Creatinine Clearance (CLCR ) Dosage Regimen in Adults
cSSSI S. aureus Bloodstream Infections
Greater 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 hours* 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.

2.7 Preparation and Administration of Daptomycin for Injection

There 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 Vial

Daptomycin 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:

  1. To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.
  2. Remove the polypropylene flip-off cap from the daptomycin for injection vial to expose the central portion of the rubber stopper.
  3. 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.
  4. 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.
  5. Ensure that all of the daptomycin for injection powder is wetted by gently rotating the vial.
    1. Allow the wetted product to stand undisturbed for 10 minutes.
    2. Gently rotate or swirl the vial contents for a few minutes, as needed, to obtain a completely reconstituted solution.

Administration Instructions

Parenteral 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:

Adults
Intravenous Injection over a period of 2 minutes

  • For intravenous injection over a period of 2 minutes in adult patients only: Administer the appropriate volume of the reconstituted daptomycin for injection (concentration of 50 mg/mL).

Intravenous Infusion over a period of 30 minutes

  • For intravenous 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 intravenous 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 intravenous 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 intravenous 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 Diluents

Stability 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°F 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.

2.8 Compatible Intravenous Solution for Reconstitution and Dilution

Daptomycin for injection is compatible with 0.9% sodium chloride injection for reconstitution.
Reconstituted daptomycin for injection can only be diluted with 0.9% sodium chloride injection.

2.9 Incompatibilities

Daptomycin 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 intravenous 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 intravenous line. If the same intravenous 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.

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