Cubicin

Lipopeptide Antibiotics

NOTE: There are 3 formulations of daptomycin that have differences concerning storage and reconstitution. Generic products may also have different storage recommendations. Carefully follow the reconstitution and storage instructions in product labeling.
For intravenous (IV) administration only.
Use a 21 gauge or smaller needle for all transfers.
Because only limited data are available regarding compatibility with other IV substances, additives or other medications should not be added to daptomycin vials or infusion bags.
Daptomycin should not be used in conjunction with ReadyMED elastomeric infusion pumps. Stability studies of daptomycin solutions stored in ReadyMED elastomeric infusion pumps identified an impurity, 2-mercaptobenzothiazole (MBT), leaching from this pump system into the daptomycin solution. MBT is used to manufacture rubber and has been reported to leach from rubber stoppers and syringe components into medicinal products. Cutaneous exposure to MBT has been associated with dermal sensitization, and chronic administration of MBT to laboratory rodents has been associated with an increased risk of certain tumors.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Cubicin RF powder vials for injection (including generics)
Reconstitution
Reconstitute a 500 mg vial with 10 mL of Sterile Water for Injection or Bacteriostatic Water for Injection. The vial solution concentration will be 50 mg/mL.
Do not reconstitute with saline products as this will result in a hyperosmotic solution that may result in infusion site reactions if the reconstituted product is administered by IV injection over 2 minutes.
Transfer the 10 mL of Sterile Water for Injection or Bacteriostatic Water for Injection through the center of the rubber stopper. Point the transfer needle against the inside wall of the vial.
Prior to use, rotate or swirl the vial for a few minutes to obtain complete reconstitution.
Vials are not preserved and are for single-use only.
For IV push injection administration, slowly remove the reconstituted 50 mg/mL solution from the vial using a polypropylene syringe with an elastomeric plunger stopper.
For intermittent IV infusion administration, further dilution is required.
Storage (vials): Follow storage recommendations in the manufacturer's instructions. Vials reconstituted with Sterile Water for Injection are stable for 1 day at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Vials reconstituted with Bacteriostatic Water for Injection are stable for 2 days at room temperature and 3 days under refrigeration.
Storage (syringes): Follow storage recommendations in the manufacturer's instructions. Solutions reconstituted with Sterile Water for Injection are stable in polypropylene syringes with an elastomeric plunger stopper for 1 day at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Solutions reconstituted with Bacteriostatic Water for Injection are stable in this syringe type for 2 days at room temperature and 5 days under refrigeration.
 
Dilution (for intermittent IV infusion)
Adults, Adolescents, and Children 7 to 17 years: Further dilute in 50 mL of 0.9% Sodium Chloride Injection.
Children 1 to 6 years: Further dilute in 25 mL of 0.9% Sodium Chloride Injection.
Storage: Follow storage recommendations in the manufacturer's instructions. Solutions reconstituted with Sterile Water for Injection that are immediately diluted with 0.9% Sodium Chloride Injection are stable for 19 hours at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Solutions reconstituted with Bacteriostatic Water for Injection that are immediately diluted with 0.9% Sodium Chloride Injection are stable for 2 days at room temperature and 5 days under refrigeration.
 
Intermittent IV Infusion
Adults, Adolescents, and Children 7 to 17 years: Infuse IV over 30 minutes.
Children 1 to 6 years: Infuse IV over 60 minutes.
Additives or other medications should not be added to daptomycin or infused simultaneously through the same IV line. If the same IV line is used for sequential infusion of different drugs, flush the line with a compatible IV solution before and after daptomycin administration.
 
Intermittent IV Push
NOTE: Daptomycin should not be administered as an IV push in pediatric patients.
Use only the reconstituted 50 mg/mL solution.
Administer via slow IV push over 2 minutes.
 
Cubicin powder vials for injection (including generics)
Reconstitution
To minimize foaming, avoid vigorous agitation or shaking of the vial during or after reconstitution.
Reconstitute the daptomycin vial with 0.9% Sodium Chloride Injection according to the manufacturer's instructions to a final concentration of 50 mg/mL.
Transfer the appropriate volume of 0.9% Sodium Chloride Injection through the center of the rubber stopper. Point the transfer needle against the inside wall of the vial.
Ensure that all the 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.
Vials are not preserved and are for single-use only.
For IV push injection administration, slowly remove the reconstituted 50 mg/mL solution from the vial using a syringe.
For intermittent IV infusion administration, further dilution is required.
Storage: Follow storage recommendations in the manufacturer's instructions. The reconstituted solution is stable in the vial for 12 hours at room temperature and up to 48 hours if stored under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Some products require protection from light.
 
Dilution (for intermittent IV infusion)
Adults, Adolescents, and Children 7 to 17 years: Further dilute in 50 mL of 0.9% Sodium Chloride Injection or other compatible solution according to the manufacturer's instructions.
Children 1 to 6 years: Further dilute in 25 mL of 0.9% Sodium Chloride Injection or other compatible solution according to the manufacturer's instructions.
Storage: Follow storage recommendations in the manufacturer's instructions. Diluted solutions are stable for 12 hours at room temperature or 48 hours under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). The combined storage time (reconstituted solution in the vial and the diluted solution in the infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration. Extended storage times may be allowed according to the manufacturer's instructions.
 
Intermittent IV Infusion
Adults, Adolescents, and Children 7 to 17 years: Infuse IV over 30 minutes.
Children 1 to 6 years: Infuse IV over 60 minutes.
Additives or other medications should not be added to daptomycin or infused simultaneously through the same IV line. If the same IV line is used for sequential infusion of different drugs, flush the line with a compatible IV solution before and after daptomycin administration.
 
Intermittent IV Push
NOTE: Daptomycin should not be administered as an IV push in pediatric patients.
Use only the reconstituted 50 mg/mL solution.
Administer via slow IV push over 2 minutes.
 
Dapzura RT powder vials for injection
Reconstitution
Reconstitute a 500 mg vial with 10 mL of Sterile Water for Injection or Bacteriostatic Water for Injection. The vial solution concentration will be 50 mg/mL.
Do not reconstitute with saline products as this will result in a hyperosmotic solution that may result in infusion site reactions if the reconstituted product is administered by IV injection over 2 minutes.
Transfer the 10 mL of Sterile Water for Injection or Bacteriostatic Water for Injection through the center of the rubber stopper. Point the transfer needle against the inside wall of the vial.
Prior to use, rotate or swirl the vial for a few minutes to obtain complete reconstitution.
Vials are not preserved and are for single-use only.
For IV push injection administration, slowly remove the reconstituted 50 mg/mL solution from the vial using a polypropylene syringe with an elastomeric plunger stopper.
For intermittent IV infusion administration, further dilution is required.
Storage (vials): Follow storage recommendations in the manufacturer's instructions. Vials reconstituted with Sterile Water for Injection are stable for 18 hours at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Vials reconstituted with Bacteriostatic Water for Injection are stable for 2 days at room temperature and 5 days under refrigeration.
Storage (syringes): Follow storage recommendations in the manufacturer's instructions. Solutions reconstituted with Sterile Water for Injection are stable in polypropylene syringes with an elastomeric plunger stopper for 18 hours at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Solutions reconstituted with Bacteriostatic Water for Injection are stable in this syringe type for 2 days at room temperature and 5 days under refrigeration.
 
Dilution (for intermittent IV infusion)
Adults, Adolescents, and Children 7 to 17 years: Further dilute in 50 mL of 0.9% Sodium Chloride Injection.
Children 1 to 6 years: Further dilute in 25 mL of 0.9% Sodium Chloride Injection.
Storage: Follow storage recommendations in the manufacturer's instructions. Solutions reconstituted with Sterile Water for Injection that are immediately diluted with 0.9% Sodium Chloride Injection are stable for 1 day at room temperature (20 to 25 degrees C or 68 to 77 degrees F) and 3 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Solutions reconstituted with Bacteriostatic Water for Injection that are immediately diluted with 0.9% Sodium Chloride Injection are stable for 2 days at room temperature and 5 days under refrigeration.
 
Intermittent IV Infusion
Adults, Adolescents, and Children 7 to 17 years: Infuse IV over 30 minutes.
Children 1 to 6 years: Infuse IV over 60 minutes.
Additives or other medications should not be added to daptomycin or infused simultaneously through the same IV line. If the same IV line is used for sequential infusion of different drugs, flush the line with a compatible IV solution before and after daptomycin administration.
 
Intermittent IV Push
NOTE: Daptomycin should not be administered as an IV push in pediatric patients.
Use only the reconstituted 50 mg/mL solution.
Administer via slow IV push over 2 minutes.

eczema vaccinatum / Delayed / 0-1.0
proteinuria / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
atrial flutter / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
eosinophilic pneumonia / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known

chest pain (unspecified) / Early / 7.0-7.0
edema / Delayed / 7.0-7.0
hypertension / Early / 6.0-6.0
elevated hepatic enzymes / Delayed / 3.0-3.0
hypotension / Rapid / 2.4-2.4
dyspnea / Early / 2.1-2.1
stomatitis / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
myopathy / Delayed / 0-1.0
eosinophilia / Delayed / 0-1.0
thrombocytosis / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
hypomagnesemia / Delayed / 0-1.0
peripheral neuropathy / Delayed / Incidence not known
hallucinations / Early / Incidence not known
dyskinesia / Delayed / Incidence not known
blurred vision / Early / Incidence not known
anemia / Delayed / Incidence not known
prolonged bleeding time / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known
bullous rash / Early / Incidence not known
dysphagia / Delayed / Incidence not known
erythema / Early / Incidence not known
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known
vaginitis / Delayed / Incidence not known
candidiasis / Delayed / Incidence not known
hyperphosphatemia / Delayed / Incidence not known

vomiting / Early / 2.7-11.0
insomnia / Early / 9.0-9.0
diarrhea / Early / 5.2-7.0
abdominal pain / Early / 2.0-6.0
pruritus / Rapid / 3.1-6.0
headache / Early / 2.7-5.4
hyperhidrosis / Delayed / 5.0-5.0
infection / Delayed / 2.4-5.0
rash / Early / 4.3-4.3
fever / Early / 3.9-3.9
dizziness / Early / 2.2-2.2
weakness / Early / 0-1.0
flushing / Rapid / 0-1.0
fatigue / Early / 0-1.0
dysgeusia / Early / 0-1.0
myalgia / Early / 0-1.0
arthralgia / Delayed / 0-1.0
muscle cramps / Delayed / 0-1.0
vertigo / Early / 0-1.0
paresthesias / Delayed / 0-1.0
ocular irritation / Rapid / 0-1.0
leukocytosis / Delayed / 0-1.0
hypoesthesia / Delayed / Incidence not known
anorexia / Delayed / Incidence not known
nausea / Early / Incidence not known
xerostomia / Early / Incidence not known
cough / Delayed / Incidence not known
vesicular rash / Delayed / Incidence not known
tinnitus / Delayed / Incidence not known

Cubicin, Cubicin RF

Rx

Intravenous, cyclic lipopeptide antibiotic
Used for susceptible gram-positive infections, including MRSA, complicated skin and skin structure infections, and bacteremia, including patients with right-sided infective endocarditis
Inactivated by pulmonary surfactant, therefore ineffective for pneumonia

6 mg/kg/dose IV every 24 hours for 2 to 6 weeks is the FDA-approved dosage. Doses of 8 to 10 mg/kg/dose IV every 24 hours may be warranted for MRSA. In patients with persistent MRSA bacteremia and vancomycin treatment failures, the clinical practice guidelines recommend 10 mg/kg/dose IV every 24 hours in combination with another agent (gentamicin, rifampin, linezolid, sulfamethoxazole/trimethoprim, or a beta-lactam). Treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia. Studies have demonstrated the safety of doses of at least 8 mg/kg/dose IV every 24 hours. Limited safety data are available for use beyond 28 days.

7 mg/kg/dose IV every 24 hours for up to 6 weeks.

9 mg/kg/dose IV every 24 hours for up to 6 weeks.

12 mg/kg/dose IV every 24 hours for up to 6 weeks.

Safety and efficacy have not been established; limited data are available. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. 6 to 10 mg/kg/dose IV every 24 hours is suggested by the Infectious Diseases Society of America (IDSA) for bacteremia. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 9 with bacteremia; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. Treat for 2 to 6 weeks for bacteremia. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.

Safety and efficacy have not been established; very limited data are available. Doses of 6 to 15 mg/kg/dose IV every 12 to 24 hours have been successfully used in case reports of neonates and premature neonates (n = 7) with MRSA and vancomycin-resistant enterococcal bacteremia. 6 mg/kg/dose IV every 12 hours is the most commonly reported dose; however, differences in peak concentrations have been observed with this dose between various studies. Doses higher than 6 mg/kg/dose may be necessary in neonates to achieve adequate drug exposure. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 9 with bacteremia; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. Treat 2 to 6 weeks for bacteremia. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.

4 mg/kg/dose IV every 24 hours for 7 to 14 days.

5 mg/kg/dose IV every 24 hours for up to 14 days.

7 mg/kg/dose IV every 24 hours for up to 14 days.

9 mg/kg/dose IV every 24 hours for up to 14 days.

10 mg/kg/dose IV every 24 hours for up to 14 days.

Safety and efficacy have not been established; limited data are available describing the use of daptomycin in pediatric patients. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 3 with complicated skin and soft tissue infections; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.

Safety and efficacy have not been established; very limited data are available. Doses of 6 to 15 mg/kg/dose IV every 12 to 24 hours have been successfully used in case reports of neonates and premature neonates (n = 7) with methicillin-resistant S. aureus and vancomycin-resistant enterococcal bacteremia. 6 mg/kg/dose IV every 12 hours is the most commonly reported dose; however, differences in peak concentrations have been observed with this dose between various studies. Doses higher than 6 mg/kg/dose may be necessary in neonates to achieve adequate drug exposure. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 3 with complicated skin and soft tissue infections; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.

4 mg/kg/dose IV every 24 hours for 5 to 14 days. 

5 mg/kg/dose IV every 24 hours for 5 to 14 days. 

7 mg/kg/dose IV every 24 hours for 5 to 14 days. 

9 mg/kg/dose IV every 24 hours for 5 to 14 days. 

10 mg/kg/dose IV every 24 hours for 5 to 14 days. 

4 mg/kg/dose IV every 24 hours for 7 to 14 days for infections due to methicillin-resistant S. aureus or in combination with other agents if a polymicrobial infection is suspected. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

4 mg/kg/dose IV every 24 hours in patients with risk factors for methicillin-resistant S. aureus.

4 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity. 

5 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity. 

7 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity. 

9 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity. 

10 mg/kg/dose IV every 24 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for Streptococcus and S. aureus infections in patients with severe penicillin hypersensitivity. 

6 mg/kg/dose IV every 24 hours for 2 to 6 weeks is the FDA-approved dosage for right-sided S. aureus endocarditis. Guidelines suggest doses of 8 to 10 mg/kg/dose IV every 24 hours for MRSA endocarditis and 10 to 12 mg/kg/dose IV every 24 hours for multi-drug resistant enterococcal endocarditis as part of combination therapy. Daptomycin is also an alternative option in patients with MSSA left-sided endocarditis. Treat native-valve S. aureus endocarditis for 6 weeks and multi-drug resistant enterococcal endocarditis for more than 6 weeks. Studies have demonstrated the safety of doses of at least 8 mg/kg/dose IV every 24 hours. Limited safety data are available for use beyond 28 days.

6 mg/kg/dose IV every 24 hours for 6 weeks is recommended by guidelines.

10 mg/kg/dose IV every 24 hours for 6 weeks is recommended by guidelines.

Safety and efficacy have not been established; limited data are available. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. 6 to 10 mg/kg/dose IV every 24 hours is suggested by the Infectious Diseases Society of America (IDSA) for infective endocarditis. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 9 with bacteremia; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. Guidelines recommend treatment for 6 weeks for endocarditis. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.

Safety and efficacy have not been established; very limited data are available. Doses of 6 to 15 mg/kg/dose IV every 12 to 24 hours have been successfully used in case reports of neonates and premature neonates (n = 7) with MRSA and vancomycin-resistant enterococcal bacteremia. 6 mg/kg/dose IV every 12 hours is the most commonly reported dose; however, differences in peak concentrations have been observed with this dose between various studies. Doses higher than 6 mg/kg/dose may be necessary in neonates to achieve adequate drug exposure. 8 mg/kg/dose IV every 24 hours was successfully used in a small study of 12 pediatric patients (n = 9 with bacteremia; age range 14 days to 7 years); microbiologic eradication was achieved in all patients and no drug-related adverse reactions occurred. Guidelines recommend treatment for 6 weeks for endocarditis. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.

Doses of 8 to 12 mg/kg/dose IV every 24 hours have been used safely and effectively in patients with vancomycin-resistant enterococci (VRE) infections, including bloodstream infections. 10 to 12 mg/kg/dose IV every 24 hours is recommended by guidelines for multi-drug resistant enterococcal endocarditis as part of combination therapy.

Safety and efficacy have not been established; limited data are available describing the use of daptomycin in pediatric patients. 8 to 10 mg/kg/dose IV every 24 hours has been recommended for VRE bacteremia. 8 mg/kg/dose IV every 24 hours was successfully used in a case report of a 10-year old girl with severe sepsis due to vancomycin- and linezolid-resistant Enterococcus faecium (VAN-B VRE).

Safety and efficacy have not been established; limited data are available describing the use of daptomycin in pediatric patients. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. One case report describes the use of daptomycin 4 mg/kg/dose IV every 12 hours in combination with linezolid in a 21-month-old child with vancomycin-resistant enterococcal bacteremia; blood cultures were sterilized 14 days after daptomycin initiation.

Safety and efficacy have not been established; limited data are available describing the use of daptomycin in pediatric patients. Based on pharmacokinetic data, doses of 8 to 10 mg/kg/dose IV every 24 hours have been recommended in this age group. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in order to ensure safe and effective therapy.

Safety and efficacy have not been established; very limited data are available. Doses of 6 to 15 mg/kg/dose IV every 12 to 24 hours have been successfully used in case reports of neonates and premature neonates (n = 7) with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococcal bacteremia. 6 mg/kg/dose IV every 12 hours is the most commonly reported dose; however, differences in peak concentrations have been observed with this dose between various studies. Doses higher than 6 mg/kg/dose may be necessary in neonates to achieve adequate drug exposure. FDA-approved labeling warns against use; animal data suggests there may be an increased risk for muscular, neuromuscular, and/or nervous system (both peripheral and central) adverse reactions in pediatric patients younger than 12 months of age. Monitoring of daptomycin serum concentrations and creatine phosphokinase (CPK) concentrations is recommended in neonates in order to ensure safe and effective therapy.

6 mg/kg/dose IV every 24 hours for at least 8 weeks, which may be followed by long-term suppressive therapy. May consider the addition of rifampin; for patients with concurrent bacteremia, add rifampin after bacteremia clearance.

7 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.

9 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.

12 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.

6 mg/kg/dose IV every 24 hours. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.

7 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

9 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

12 mg/kg/dose IV every 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

6 mg/kg/dose IV every 24 hours in combination with rifampin for 2 to 6 weeks, followed by oral step-down therapy, which may be followed by long-term suppressive therapy.

6 mg/kg/dose IV every 24 hours plus rifampin followed by long-term oral therapy.

6 mg/kg/dose IV every 24 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

7 mg/kg/dose IV every 24 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

9 mg/kg/dose IV every 24 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

12 mg/kg/dose IV every 24 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

6 to 8 mg/kg/dose IV every 24 hours for 6 weeks.

6 mg/kg/dose IV every 24 hours for 6 weeks. Add an aminoglycoside for 4 to 6 weeks in patients with endocarditis or bacteremia; may consider shorter aminoglycoside duration in patients with bacteremia.

6 mg/kg/dose IV every 24 hours for 4 to 6 weeks with or without an aminoglycoside, which may be followed by long-term suppressive therapy.

6 mg/kg/dose IV every 24 hours is recommended by clinical practice guidelines for patients with suspected MRSA, vancomycin-resistant pathogens (VRE), or when vancomycin is not an option. Daptomycin as part of combination therapy with an antibiotic that has gram negative coverage has been successfully used in patients with febrile neutropenia in small studies.

4 to 6 mg/kg/dose IV every 24 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

4 to 6 mg/kg/dose IV every 24 hours as part of combination therapy for at least 5 to 7 days as an alternative.

100 mg/L intraperitoneal loading dose, followed by 20 mg/L in each dialysate exchange. Treat for 21 days.

†Indicates off-label use

No dosage adjustment is required in patients with mild to moderate hepatic impairment; however, the pharmacokinetics in patients with severe hepatic impairment (Child-Pugh class C) have not been evaluated.

Adults
CrCl 30 mL/minute or more: No dosage adjustment required.
CrCl less than 30 mL/minute: Extend the dosing interval to every 48 hours.
 
Pediatric patients†
The following dose adjustments, based on a dose of 6 mg/kg/dose IV every 24 hours, have been recommended.
CrCl 30 mL/minute/1.73 m2 or more: No dosage adjustment required.
CrCl 10 to 29 mL/minute/1.73 m2: 4 mg/kg/dose IV every 24 hours.
CrCl less than 10 mL/minute/1.73 m2: 4 mg/kg/dose IV every 48 hours.
 
Neonates†
A dose of 6 mg/kg/dose IV every 24 hours was successfully used in a full-term neonate with renal impairment (serum creatinine 0.6 mg/dL) and vancomycin-resistant enterococcal bacteremia. The patient received an 8-week course of daptomycin, including 6 weeks after the last positive blood culture.
 
Intermittent hemodialysis
Adults
Extend the dosing interval to every 48 hours. When possible, the daptomycin dose should be given after hemodialysis on hemodialysis days.
 
Pediatric patients†
4 mg/kg/dose IV every 48 hours after dialysis.
 
Continuous renal replacement therapy (CRRT)†
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.[42303]
 
Adults
4 to 8 mg/kg IV every 24 hours or 8 mg/kg IV every 48 hours. General recommendations for patients receiving CVVH, CVVHD, and CVVHDF suggest 4 or 6 mg/kg/dose IV every 48 hours. However, some experts state that dose may result in underdosing and suggest 4 to 6 mg/kg IV every 24 hours or 8 mg/kg IV every 48 hours. More specific recommendations for CVVH, CVVHD, and CVVHDF based on ultrafiltrate rate (UFR) suggest 6 to 8 mg/kg IV every 24 hours for patients receiving an UFR of 1 to 2 L/hour and 8 mg/kg IV every 24 hours for patients receiving an UFR of at least 3 L/hour. Doses more than 8 mg/kg IV every 24 hours increase the risk of CPK elevations and myopathy. Use clinical judgment and frequent monitoring if pursuing doses of 10 to 12 mg/kg IV every 24 hours in patients receiving an UFR of at least 3 L/hour.
 
Pediatric patients†
8 mg/kg/dose IV every 48 hours.
 
Hybrid hemodialysis†
NOTE: Hybrid treatments include prolonged intermittent renal replacement therapy (PIRRT), sustained low-efficiency dialysis (SLED), slow extended daily dialysis/diafiltration (SLEDD-f), and extended daily dialysis (EDD). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), the type of infection, the duration of renal replacement therapy, the ultrafiltration rate, the dialysis flow rate, and how often dialysis sessions occur.[65397]
 
Adults
In a single-dose pharmacokinetic study in 10 critically ill patients receiving an 8-hour EDD session, daptomycin 6 mg/kg IV was administered 8 hours prior to dialysis. Daptomycin half-life in these critically ill patients was comparable to healthy controls. The mean fraction of drug removal by a single dialysis treatment was 23.3%. The authors recommended 6 mg/kg IV every 24 hours if administered within 8 hours of EDD initiation to decrease the risk of treatment failure.
 
Peritoneal dialysis
Adults
Extend the dosing interval to every 48 hours.
 
Pediatric patients†
4 mg/kg/dose IV every 48 hours.

HMG-CoA reductase inhibitors: (Major) Temporarily suspend HMG-CoA reductase inhibitors in patients taking daptomycin as cases of rhabdomyolysis have been reported with concomitant use. Both agents can cause myopathy and rhabdomyolysis when given alone and the risk may be increased when given together.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Red Yeast Rice: (Moderate) Certain red yeast rice products (i.e., pre-2005 Cholestin formulations) contain lovastatin. HMG-CoA reductase inhibitors such as lovastatin are known to cause myopathy. Elevated CPK has been reported in clinical trials of daptomycin, a lipopeptide antibiotic. In a placebo-controlled phase I trial of daptomycin that included 10 healthy subjects stabilized on simvastatin therapy, there was no increase in the incidence of adverse reactions nor was myopathy reported. However, data regarding coadministration of daptomycin with HMG-CoA reductase inhibitors are limited; temporary suspension of HMG-CoA reductase inhibitor therapy should be considered in patients receiving daptomycin.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Tobramycin: (Moderate) The pharmacokinetics of daptomycin and tobramycin may be altered when the two antibiotics are coadministered. The serum concentration of daptomycin may be increased and the serum concentration of tobramycin may be decreased. The manufacturer recommends caution when daptomycin is coadministered with tobramycin.
Warfarin: (Moderate) Monitor patients for signs and symptoms of bleeding during coadministration. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary. The concomitant use of warfarin with antibiotics may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. In 16 healthy adults, a 5-day daptomycin course coadministered with a single oral dose of warfarin (25 mg) on the fifth day had no significant effect on the pharmacokinetics of either drug and did not significantly alter the INR; however, there are no data describing concurrent use beyond a single warfarin dose.

Cubicin/Cubicin RF/Daptomycin Intravenous Inj Pwd F/Sol: 350mg, 500mg
Daptomycin Intravenous Inj Sol: 50mL, 100mL, 350mg, 500mg, 700mg, 1000mg

6 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 12 mg/kg/dose IV every 24 hours have been used off-label.

6 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 12 mg/kg/dose IV every 24 hours have been used off-label.

7 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 10 mg/kg/dose IV every 24 hours have been used off-label.

12 years: 7 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 10 mg/kg/dose IV every 24 hours have been used off-label.
7 to 11 years: 9 mg/kg/dose IV every 24 hours is FDA-approved maximum dosage; however, doses up to 10 mg/kg/dose IV every 24 hours have been used off-label.
1 to 6 years: 12 mg/kg/dose IV every 24 hours.

Safety and efficacy have not been established; doses up to 10 mg/kg/dose IV every 24 hours have been used off-label.

Safety and efficacy have not been established; doses up to 15 mg/kg/dose IV every 12 hours have been used off-label.

Lipopeptide antibiotics, like daptomycin, interfere with the integrity of cell wall structure in gram-positive bacteria via a unique mechanism of action. Specifically, lipopeptides bind to bacterial membranes and cause a rapid depolarization of membrane potential; they do not penetrate the bacterial cytoplasm. This loss of membrane potential leads to inhibition of protein, DNA, and RNA synthesis and, eventually, bacterial cell death. Lipopeptides appear to be bactericidal against gram-positive bacteria.[29273]
 
Ironically, the unique mechanism of action of daptomycin causes it to be inactivated by pulmonary surfactant. Pulmonary surfactant is primarily dipalmitoylphosphatidylcholine with significant amounts of phosphatidylglycerol, which is also a prominent component of gram-positive bacterial membranes. These phospholipids interact with daptomycin and sequester the antibiotic, thereby preventing it from exerting its antibacterial effects.[32686] Phase 3 clinical trials in adults with community-acquired pneumonia showed reduced efficacy of daptomycin.[29273]
 
Daptomycin displays rapid, concentration-dependent bactericidal activity against gram-positive bacteria and a post-antibiotic effect (PAE). Concentration-dependent killing describes the principle that bactericidal effects increase as the concentration increases. PAE is where suppression of bacterial growth continues after the antibiotic concentration falls below the bacterial MIC. Based on animal models, the pharmacokinetic/pharmacodynamic (PK/PD) activity of daptomycin appears to correlate best with the area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio for certain pathogens, including S. aureus. The principal PK/PD parameter associated with clinical success has not been determined by trials.[29273] [55016]
 
The susceptibility interpretive criteria for daptomycin are delineated by pathogen. The MICs are defined for beta-hemolytic streptococci, Streptococcus sp. viridans group, and Staphylococcus sp. as susceptible at 1 mcg/mL or less. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterococcus sp. The MICs are defined by the FDA for Enterococcus faecalis (including vancomycin-resistant isolates) as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL. The MICs are defined by CLSI for Enterococcus faecium as susceptible-dose dependent (SDD) at 4 mcg/mL or less and resistant at 8 mcg/mL or more (based on a dosage of 8 to 12 mg/kg IV every 24 hours). The MICs are defined by CLSI for other Enterococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more. Susceptibility test interpretive criteria (STIC) are based on a dosage of 6 mg/kg IV once every 24 hours for patients with a CrCl more than 30 mL/minute for all isolates except E. faecium MICs as defined by CLSI. MICs are not intended to be used for respiratory isolates.[63320] [63321]
 
Nonsusceptible isolates have emerged during daptomycin therapy. Mechanisms of resistance are not clearly defined; however, single-point mutations in mprF, the lysylphosphatidyglycerol synthetase gene, have been present in resistant strains. Additionally, prior exposure to vancomycin and elevated vancomycin MICs have been associated with increases in daptomycin MICs, which may suggest possible cross-resistance.[46693]

Daptomycin is administered intravenously. Protein binding is approximately 90% to 93%, primarily to albumin, and is reversible; it is not altered by daptomycin concentration, dose, or number of doses received. In patients with significant renal impairment, protein binding is decreased. Daptomycin is distributed into lung tissue; however, it is inhibited by pulmonary surfactant. The steady-state volume of distribution in healthy adults is approximately 0.1 L/kg. The metabolism of daptomycin has not been determined; however, inactive metabolites have been identified in the urine. Daptomycin is primarily (78%) excreted by the kidneys; 5.7% of a dose is excreted in the feces. The clearance and elimination half-life of daptomycin in adults is approximately 7 to 9 mL/hour/kg and 8 to 9 hours, respectively.
 
Affected cytochrome P450 isoenzymes: none
In vitro studies have shown that daptomycin is not metabolized by human liver microsomes. In vitro studies have also shown that daptomycin does not induce or inhibit the following CYP450 enzymes: 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A4.

After a 30 minute intravenous infusion of daptomycin, the maximum serum concentrations (Cmax) occur in about 30 to 60 minutes (Tmax). The Cmax is approximately 57.8 mcg/mL for a dose of 4 mg/kg, 93.9 mcg/mL for a dose of 6 mg/kg, 123.3 mcg/mL for a dose of 8 mg/kg, 141.1 mcg/mL for a dose of 10 mg/kg, and 183.7 mcg/mL for a dose of 12 mg/kg. The AUC is 494 mcg x hour/mL for a dose of 4 mg/kg, 632 mcg x hour/mL for a dose of 6 mg/kg, 858 mcg x hour/mL for a dose of 8 mg/kg, 1,039 mcg x hour/mL for a dose of 10 mg/kg, and 1,277 mcg x hour/mL for a dose of 12 mg/kg. The Cmax in inflammatory fluid has a Tmax of about 4 hours. Steady state serum concentrations are obtained in about 3 days. After administration of daptomycin over a 2 minute period, the steady-state AUC value is approximately 475 mcg x hour/mL for a 4 mg/kg dose and 701 mcg x hour/mL for a 6 mg/kg dose. The Cmax for these doses was simulated to be 77.7 mcg/mL for the 4 mg/kg dose and 116.6 mcg/mL for the 6 mg/kg dose.

Data on the use of daptomycin in human pregnancy are insufficient to inform a drug-associated risk for major birth defects and miscarriage. Daptomycin was not teratogenic in rats and rabbits at exposures significantly higher (75 mg/kg/day) than the expected human exposure; maternal toxicity, including decreased body weight gain and food consumption, was observed at the highest dose.  Due to a high molecular weight, placental crossing of daptomycin is expected to be limited. However, vancomycin, which is similar in molecular weight to daptomycin, crosses the placenta in the second trimester resulting in detectable concentrations in amniotic fluid and cord blood.

Daptomycin is excreted in human milk. There are no data on the effects of daptomycin on the breast-fed infant or milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for daptomycin and any potential adverse effects on the breast-fed infant from daptomycin or the underlying maternal condition.[29273] [46784] In 1 patient treated for a pelvic infection with daptomycin (6.7 mg/kg IV) and ertapenem for 28 days, daptomycin breast-milk concentrations were obtained on day 27 of therapy. Concentrations were highest at 8 hours after the dose with a concentration of 44.7 mcg/L. At 20 hours after the dose, a concentration of 29.2 mcg/L was obtained, and the final sample had no detectable drug (less than 25 mcg/L). Estimated milk:plasma ratio was 0.0012.[46784] Vancomycin, clindamycin, and sulfamethoxazole; trimethoprim may be potential alternatives to consider during breast-feeding. However, assess site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility before choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal.[28468] [40955] Alternative antimicrobials that previous American Academy of Pediatrics recommendations considered as usually compatible with breast-feeding include clindamycin and sulfamethoxazole; trimethoprim.[27500]