Daptomycin In Sodium Chloride
Daptomycin In Sodium Chloride Prescribing Information
Daptomycin in Sodium Chloride 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) for whom appropriate dosing can be achieved () and,1.1 Complicated Skin and Skin Structure Infections (cSSSI)Daptomycin in Sodium Chloride Injection is indicated for the treatment of adult and pediatric patients (1 to 17 years of age) for whom appropriate dosing can be achieved, 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 dysgalactiaesubsp.equisimilis,andEnterococcus faecalis(vancomycin-susceptible isolates only).• Staphylococcus aureusbloodstream infections (bacteremia), in adult patients for whom appropriate dosing can be achieved, 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 in Sodium Chloride Injection is indicated for the treatment of adult patients for whom appropriate dosing can be achieved, 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) for whom appropriate dosing can be achieved. ()1.3Staphylococcus aureusBloodstream Infections (Bacteremia) in Pediatric Patients (1 to 17 Years of Age)Daptomycin in Sodium Chloride Injection is indicated for the treatment of pediatric patients (1 to 17 years of age) for whom appropriate dosing can be achieved with
Staphylococcus aureusbloodstream infections (bacteremia).
Limitations of Use
• Daptomycin in Sodium Chloride Injection is not indicated for the treatment of pneumonia. ()1.4 Limitations of UseDaptomycin in Sodium Chloride Injection is not indicated for the treatment of pneumonia.
Daptomycin in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride Injection is not indicated for the treatment of left-sided infective endocarditis due to S. aureus. ()1.4 Limitations of UseDaptomycin in Sodium Chloride Injection is not indicated for the treatment of pneumonia.
Daptomycin in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride Injection is not indicated for the treatment of pneumonia.
Daptomycin in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride Injection and other antibacterial drugs, Daptomycin in Sodium Chloride 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 in Sodium Chloride Injection and other antibacterial drugs, Daptomycin in Sodium Chloride 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.
If a dose of Daptomycin in Sodium Chloride Injection is required that does not equal 350 mg, 500 mg, 700 mg or 1,000 mg, this product is not recommended for use and an alternative formulation of daptomycin should be considered. (
If a dose of Daptomycin in Sodium Chloride Injection is required that does not equal 350 mg, 500 mg, 700 mg or 1,000 mg, this product is not recommended for use and an alternative formulation of daptomycin should be considered.
Administer the appropriate dose of Daptomycin in Sodium Chloride Injection to adult patients by intravenous infusion over a thirty (30) minute period
• Pediatric Patients 7 to 17 years of Age:Administer Daptomycin in Sodium Chloride 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 in Sodium Chloride Injection intravenously by infusion over a 60-minute period[see Dosage and Administration (2.3, 2.5, 2.7)].
• Administer to adult patients intravenously by infusion over a 30-minute period. (,2.1 Important Administration Duration InstructionsIf a dose of Daptomycin in Sodium Chloride Injection is required that does not equal 350 mg, 500 mg, 700 mg or 1,000 mg, this product is not recommended for use and an alternative formulation of daptomycin should be considered.
Adult Patients:Administer the appropriate dose of Daptomycin in Sodium Chloride Injection to adult patients by intravenous infusion over a thirty (30) minute period
[see Dosage and Administration (2.2, 2.4, 2.7)].Pedatric Patients (1 to 17 Years of Age)• Pediatric Patients 7 to 17 years of Age:Administer Daptomycin in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride InjectionThawing of Plastic Container• Thaw frozen container at room temperature 20°C to 25°C (68°F to 77°F) or under refrigeration 2°C to 8°C (36°F to 46°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw.• No further dilution is necessary.• Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.• Do not add supplementary medication.• The container should be visually inspected. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired.• Thaw and equilibrate container to a room temperature.• Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded.• Solution should be clear and slightly yellow in color.• The thawed solution is stable for 30 days under refrigeration (5°C/41°F) or 48 hours at room temperature (25°C/77°F).Do not refreeze thawed antibacterial drugs.
Preparation for Administration• Suspend container from support.• Remove protector from outlet port at bottom of container.• Attach Intravenous administration set to outlet port. Refer to the manufacturer’s instructions accompanying the administration set for complete directions.
Administration InstructionsParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
AdultsIntravenous Infusion over a period of 30 minutes• For intravenous infusion over a period of 30 minutes in adult patients: The appropriate dose of Daptomycin in Sodium Chloride Injection should be used, based on patient weight.
Pediatric Patients (1 to 17 Years of Age)Intravenous Infusion over a period of 30 or 60 minutes• For Intravenous infusion over a period of 60 minutes in pediatric patients 1 to 6 years of age:The appropriate dose of Daptomycin in Sodium Chloride Injection should be used, based on patient weight. The infusion rate should be maintained at 0.83 mL/min for a 50 mL GALAXY container and 1.67 mL/min for a 100 mL GALAXY container 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 dose of Daptomycin in Sodium Chloride Injection should be used, based on patient weight. The infusion rate should be maintained at 1.67 mL/min for a 50 mL GALAXY container and 3.33 mL/min for a 100 mL GALAXY container over the 30-minute period.
Do not exceed the In-Use storage conditions of Daptomycin in Sodium Chloride Injection described below. Discard unused portions of Daptomycin in Sodium Chloride Injection.
In-Use Storage Conditions for Daptomycin in Sodium Chloride InjectionThe thawed solution is stable for 30 days under refrigeration (5°C/41°F) or 48 hours at 25°C/77°F.
Do not refreeze thawed antibacterial drugs.• Recommended dosage regimen for adult patients (,2.2 Dosage in Adults for cSSSIAdminister Daptomycin in Sodium Chloride Injection 4 mg/kg to adult patients intravenously 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 in Sodium Chloride Injection 6 mg/kg to adult patients intravenously 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 in Sodium Chloride 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 . When possible, Daptomycin in Sodium Chloride 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 in Sodium Chloride Injection in Adult Patients Creatinine Clearance(CLCR)Dosage Regimen in AdultscSSSIS. 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 hours*
6 mg/kg once every 48 hours*
*When possible, administer Daptomycin in Sodium Chloride Injection following the completion of hemodialysis on hemodialysis days.
Pediatric Patients:The dosage regimen for Daptomycin in Sodium Chloride Injection in pediatric patients with renal impairment has not been established.
| Creatinine Clearance (CLCR) | Dosage Regimen | |
|---|---|---|
cSSSI For 7 to 14 days | S. aureus BacteremiaFor 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 hours* | 6 mg/kg once every 48 hours* |
*Administered following hemodialysis on hemodialysis days. | ||
• Administer to pediatric patients intravenously by infusion over a 30- or 60-minute period, based on age. (,2.1 Important Administration Duration InstructionsIf a dose of Daptomycin in Sodium Chloride Injection is required that does not equal 350 mg, 500 mg, 700 mg or 1,000 mg, this product is not recommended for use and an alternative formulation of daptomycin should be considered.
Adult Patients:Administer the appropriate dose of Daptomycin in Sodium Chloride Injection to adult patients by intravenous infusion over a thirty (30) minute period
[see Dosage and Administration (2.2, 2.4, 2.7)].Pedatric Patients (1 to 17 Years of Age)• Pediatric Patients 7 to 17 years of Age:Administer Daptomycin in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride InjectionThawing of Plastic Container• Thaw frozen container at room temperature 20°C to 25°C (68°F to 77°F) or under refrigeration 2°C to 8°C (36°F to 46°F). Product should not be thawed by immersion in water baths or by microwave irradiation. Do not force thaw.• No further dilution is necessary.• Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.• Do not add supplementary medication.• The container should be visually inspected. If the outlet port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired.• Thaw and equilibrate container to a room temperature.• Agitate after solution has reached room temperature. If after visual inspection the solution remains cloudy or if an insoluble precipitate is noted or if any seals are not intact, the container should be discarded.• Solution should be clear and slightly yellow in color.• The thawed solution is stable for 30 days under refrigeration (5°C/41°F) or 48 hours at room temperature (25°C/77°F).Do not refreeze thawed antibacterial drugs.
Preparation for Administration• Suspend container from support.• Remove protector from outlet port at bottom of container.• Attach Intravenous administration set to outlet port. Refer to the manufacturer’s instructions accompanying the administration set for complete directions.
Administration InstructionsParenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
AdultsIntravenous Infusion over a period of 30 minutes• For intravenous infusion over a period of 30 minutes in adult patients: The appropriate dose of Daptomycin in Sodium Chloride Injection should be used, based on patient weight.
Pediatric Patients (1 to 17 Years of Age)Intravenous Infusion over a period of 30 or 60 minutes• For Intravenous infusion over a period of 60 minutes in pediatric patients 1 to 6 years of age:The appropriate dose of Daptomycin in Sodium Chloride Injection should be used, based on patient weight. The infusion rate should be maintained at 0.83 mL/min for a 50 mL GALAXY container and 1.67 mL/min for a 100 mL GALAXY container 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 dose of Daptomycin in Sodium Chloride Injection should be used, based on patient weight. The infusion rate should be maintained at 1.67 mL/min for a 50 mL GALAXY container and 3.33 mL/min for a 100 mL GALAXY container over the 30-minute period.
Do not exceed the In-Use storage conditions of Daptomycin in Sodium Chloride Injection described below. Discard unused portions of Daptomycin in Sodium Chloride Injection.
In-Use Storage Conditions for Daptomycin in Sodium Chloride InjectionThe thawed solution is stable for 30 days under refrigeration (5°C/41°F) or 48 hours at 25°C/77°F.
Do not refreeze thawed antibacterial drugs.• 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 cSSSIIf a dose of Daptomycin in Sodium Chloride Injection is required that does not equal 350 mg, 500 mg, 700 mg or 1,000 mg, this product is not recommended for use and an alternative formulation of daptomycin should be considered. The recommended dosage regimens based on age for pediatric patients with cSSSI are shown in Table 1. Administer Daptomycin in Sodium Chloride Injection intravenously once every 24 hours for up to 14 days.
Table 1. Recommended Dosage of Daptomycin in Sodium Chloride Injection in Pediatric Patients (1 to 17 Years of Age) with cSSSI, Based on Age Age RangeDosage Regimen*Duration of therapy12 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.
| Age group | Dosage* | 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 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. | ||
• Recommended dosage regimen for pediatric patients (1 to 17 years of age) with S. aureus bacteremia, based on age ():2.5 Dosage in Pediatric Patients (1 to 17 Years of Age) withStaphylococcus aureusBloodstream Infections (Bacteremia)If a dose of Daptomycin in Sodium Chloride Injection is required that does not equal 350 mg, 500 mg, 700 mg or 1,000 mg, this product is not recommended for use and an alternative formulation of daptomycin should be considered. The recommended dosage regimens based on age for pediatric patients with
S. aureusbloodstream infections (bacteremia) are shown in Table 2. Administer Daptomycin in Sodium Chloride Injection intravenously once every 24 hours for up to 42 days.Table 2. Recommended Dosage of Daptomycin in Sodium Chloride Injection in Pediatric Patients (1 to 17 Years of Age) with S. aureus Bacteremia, Based on Age AgeDosage*Duration of therapy12 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.
| 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. | ||
Injection: Daptomycin in Sodium Chloride injection is a frozen, premixed, iso-osmotic, sterile, nonpyrogenic solution in the GALAXY container.
• 350 mg/50 mL (7 mg/mL): Each 50 mL single-dose GALAXY container contains 350 mg daptomycin in sodium chloride.• 500 mg/50 mL (10 mg/mL): Each 50 mL single-dose GALAXY container contains 500 mg daptomycin in sodium chloride.• 700 mg/100 mL (7 mg/mL): Each 100 mL single-dose GALAXY container contains 700 mg daptomycin in sodium chloride.• 1,000 mg/100 mL (10 mg/mL): Each 100 mL single-dose GALAXY container contains 1,000 mg daptomycin in sodium chloride.
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.
In pregnant rats, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 18. Maternal body weight gain was decreased at 75 mg/kg/day. No embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than in humans at the recommended maximum dose of 6 mg/kg (based on body surface area).
In pregnant rabbits, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 15. Maternal body weight gain and food consumption were decreased at 75 mg/kg/day. No embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 4-fold higher than in humans at the maximum recommended dose of 6 mg/kg (based on body surface area).
In a combined fertility and pre/postnatal development study, daptomycin was administered intravenously to female rats at doses of 2, 25, 75 mg/kg/day from 14-days pre-mating through lactation/postpartum day 20). No effects on pre/postnatal development were observed up to the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than the maximum recommended human dose of 6 mg/kg (based on body surface area)1.
Daptomycin in Sodium Chloride 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 in Sodium Chloride Injection occurs, discontinue the drug and institute appropriate therapy
• Anaphylaxis/hypersensitivity reactions (including life-threatening): Discontinue Daptomycin in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride Injection should be monitored for the development of muscle pain or weakness, particularly of the distal extremities. In patients who receive Daptomycin in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride Injection should not be dosed more frequently than once a day.
Daptomycin in Sodium Chloride 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 in Sodium Chloride Injection
[see Drug Interactions (7.1)].• Eosinophilic pneumonia: Discontinue Daptomycin in Sodium Chloride 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 in Sodium Chloride Injection should undergo prompt medical evaluation, and Daptomycin in Sodium Chloride Injection should be discontinued immediately. Treatment with systemic steroids is recommended.• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue Daptomycin in Sodium Chloride 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 in Sodium Chloride Injection should undergo medical evaluation. If DRESS is suspected, discontinue Daptomycin in Sodium Chloride Injection promptly and institute appropriate treatment.• Tubulointerstitial Nephritis (TIN): Discontinue Daptomycin in Sodium Chloride 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 in Sodium Chloride Injection should undergo medical evaluation. If TIN is suspected, discontinue Daptomycin in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride 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 in Sodium Chloride 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 relapsingS. 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 4shows 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) CLCRSuccess Rate n/N (%)Daptomycin for Injection for Injection
4 mg/kg every 24hComparator50-70 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 5was 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) Success Rate n/N (%)Baseline CLCRDaptomycin for Injection
6 mg/kg every 24hComparatorBacteremiaRight-SidedInfective EndocarditisBacteremiaRight-SidedInfective 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.