Note: The manufacturer recommends avoiding use in patients <12 months due to musculoskeletal, neuromuscular, and nervous system adverse effects observed in neonatal canine models. Daptomycin should not be used for the treatment of pneumonia due to inactivation of antimicrobial activity by pulmonary surfactant (Silverman 2005).
Gram-positive infection, severe: Very limited data available: IV: 6 mg/kg/dose every 12 hours (Bradley 2019; Cohen-Wolkowiez 2008; Sarafidis 2010). Dosing based on several case reports and a pharmacokinetic study. This dosing was used for 10 to 17 days in 3 neonates [patient age: PMA: 32 weeks (PNA: 8 weeks), PMA: 35 weeks (PNA: 3 weeks) and PMA: 32 weeks (PNA: 38 days)] with normal renal function (Cohen-Wolkowiez 2008; Sarafidis 2010). A pharmacokinetic study of 20 neonates and infants [GA: Median: 32 weeks (range: 23 to 40 weeks); PNA: Median: 3 days (range: 1 to 85 days)] evaluated a single 6 mg/kg dose and reported median AUC exposure ~60% of that achieved in adults with standard adult dosing and a faster clearance than adults and adolescents (Cohen-Wolkowiez 2012). A once-daily dose of 10 mg/kg, increased to 15 mg/kg on treatment day 6 for a total duration of 14 days, successfully treated a neonate (PMA: 31 weeks; PNA: 28 days) with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (Hussain 2011).
Dosing adjustment in renal impairment: Data limited to case reports: In a full-term neonate (PNA: 41 days) with impaired kidney function (SCr: 0.9 mg/dL), an initial dose of 4 mg/kg/dose every 48 hours was used; dose was increased to 6 mg/kg/dose every 36 hours upon a decrease in serum creatinine (SCr: 0.6 mg/dL) and lower than desired daptomycin peak concentration; dose was further increased to 6 mg/kg/dose every 24 hours due to persistent positive cultures; after a week on the higher dose, blood cultures became negative (Beneri 2008). In one 24-week GA neonate (PNA 25 days) with impaired kidney function (SCr 2.6 mg/dL), 6 mg/kg/dose every 12 hours was administered throughout the course of therapy (drug was continued for 14 days after first negative culture). Peak and trough concentrations were similar to those previously reported in neonates, and CPK was monitored throughout; no adverse effects were reported (Gawronski 2015).
Note: Daptomycin should not be used for the treatment of pneumonia due to inactivation of antimicrobial activity by pulmonary surfactant (Silverman 2005). The manufacturer recommends avoiding use in patients <12 months due to musculoskeletal, neuromuscular, and nervous system adverse effects observed in neonatal canine models. Approved ages and uses for generic products may vary; consult labeling for specific information.
General dosing, susceptible organisms (severe infection): Limited data available:
Infants: Very limited data available; due to insufficient pharmacokinetic data, optimal dosing not established:
Young infants (eg, <2 months of age): IV: 6 mg/kg/dose every 12 hours (Bradley 2019); dosing was reported in a case-series including former premature and term neonates (n=3, PNA at treatment: 4 to 12 weeks; weight at treatment: 2 to 4.4 kg); one infant required a dose of 15 mg/kg/dose every 12 hours for endocarditis (Antachopoulos 2012).
Infants: IV: Reported range: 8 to 10 mg/kg/dose every 24 hours (Red Book [AAP 2018]; Tedeschi 2016).
Children ≤6 years: 10 mg/kg/dose every 24 hours (Red Book [AAP 2018]). Note: Higher doses may be necessary depending on indication.
Children ≥7 years and Adolescents: 4 to 6 mg/kg/dose every 24 hours (Red Book [AAP 2018]). Note: Higher doses may be necessary depending on indication.
Bacteremia, due to susceptible Staphylococcus aureus :
Children and Adolescents: Treatment duration variable based on source and clinical response; typically ≥14 days is recommended for S. aureus bacteremia; in trials, total treatment duration (IV and oral step-down therapy) was 5 to 28 days in patients <12 years of age and 5 to 42 days in patients 12 to 17 years of age (Arrieta 2018; Red Book [AAP 2018]).
Children ≤6 years: IV: 12 mg/kg/dose every 24 hours.
Children: 7 to ≤11 years: IV: 9 mg/kg/dose every 24 hours.
Children ≥12 years and Adolescents ≤17 years: IV: 7 mg/kg/dose every 24 hours.
Adolescents ≥18 years: IV: 6 mg/kg/dose every 24 hours.
Endocarditis due to Staphylococcus (methicillin-resistant S. aureus [MRSA] or vancomycin resistant/intolerant), treatment (AHA [Baltimore 2015]): Note: Based on more recent pharmacokinetic/dynamic experience in pediatric patients (Arrieta 2018), AHA guideline dosing (AHA [Baltimore 2015]) may not be adequate and higher doses necessary in some patients.
Children <6 years: IV: 10 mg/kg/dose every 24 hours.
Children ≥6 years and Adolescents: 6 mg/kg/dose every 24 hours.
Osteomyelitis, acute hematogenous (AHO): Limited data available:
Children ≤6 years: IV: 12 mg/kg/dose every 24 hours.
Children 7 to ≤11 years: IV: 9 mg/kg/dose every 24 hours.
Children ≥12 years and Adolescents ≤17 years: IV: 7 mg/kg/dose every 24 hours.
Dosing based on a randomized, controlled, non-inferiority trial (n=146, n=74 received daptomycin; ages: 1.2 to 17.3 years) comparing daptomycin to comparator (chosen based on local antibiogram) for AHO. Pathogens were isolated in 62.2% of patients receiving daptomycin (methicillin-susceptible S. aureus [MSSA]: 84.8%; MRSA: 8.7%). The primary objective of clinical improvement on or before day 5 occurred in 77.5% of patients receiving daptomycin and 82.9% of patients receiving comparator. Adverse events were reported more frequently in comparator (62.5%) compared to daptomycin (45.9%). In the United States, median IV treatment duration for daptomycin was 4 days (range: 1 to 21 days) before transitioning to oral step-down therapy (Bradley 2020).
Skin and skin structure infections; complicated (cSSSI) due to susceptible S. aureus :
Children: 1 to <2 years: IV: 10 mg/kg/dose every 24 hours.
Children: 2 to ≤6 years: IV: 9 mg/kg dose every 24 hours.
Children: 7 to ≤11 years: IV: 7 mg/kg/dose every 24 hours.
Children ≥12 years and Adolescents ≤17 years: IV: 5 mg/kg/dose every 24 hours.
Adolescents ≥18 years: IV: 4 mg/kg/dose every 24 hours.
Treatment duration: Up to 14 days (manufacturer's labeling); in clinical trials, the median duration of IV therapy was 3 days (range: 1 to 10 days) and the median duration of total therapy (IV plus oral step-down therapy) was 12 days (range: 1 to 35 days) (Bradley 2017).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: There are no pediatric-specific recommendations in the manufacturer's labeling (has not been studied). The following dosage adjustments have been recommended (Aronoff 2007): Note: Renally adjusted dose recommendations are based on doses of 6 mg/kg/dose every 24 hours. IV:
GFR >30 mL/minute/1.73 m2: Administer full dose
GFR 10 to 29 mL/minute/1.73 m2: 4 mg/kg/dose every 24 hours; one case series using a normal dose of 8 mg/kg/dose every 24 hours, decreased the frequency to every 48 hours (same dose) for pediatric patients <12 years with CrCl <30 mL/minute (Tedeschi 2016); in a retrospective report, a pediatric subject with CrCl <30 mL/minute received 4 mg/kg/dose and had the dosing interval extended to every 48 hours (Ardura 2007)
GFR <10 mL/minute/1.73 m2: 4 mg/kg/dose every 48 hours
Hemodialysis: 4 mg/kg/dose every 48 hours after dialysis
Peritoneal dialysis: 4 mg/kg/dose every 48 hours
Continuous renal replacement therapy (CRRT): 8 mg/kg/dose every 48 hours; monitor CPK weekly
Children and Adolescents:
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
(For additional information see "Daptomycin: Drug information")
Note: Daptomycin should not be used for the treatment of pneumonia due to inactivation of antimicrobial activity by pulmonary surfactant (Silverman 2005).
Bloodstream infection:
Empiric or pathogen-directed therapy for methicillin-resistant Staphylococcus aureus : IV: 6 to 8 mg/kg once daily (IDSA [Liu 2011]; IDSA [Mermel 2009]); some experts recommend 8 to 10 mg/kg once daily (IDSA [Liu 2011]; Lowy 2022; Timbrook 2018). For persistent or refractory cases or isolates with reduced susceptibility, use as part of an appropriate combination regimen (Cortes-Penfield 2018; Dhand 2011; Geriak 2019; Lowy 2022; Sakoulas 2014). Treat uncomplicated S. aureus bacteremia for ≥14 days from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (IDSA [Mermel 2009]).
Empiric or pathogen-directed therapy for methicillin-resistant Staphylococcus epidermidis (alternative agent) (off-label use) : IV: 6 mg/kg once daily (IDSA [Mermel 2009]); some experts recommend 8 to 10 mg/kg once daily (Tufariello 2020). Treat uncomplicated bacteremia for 5 to 7 days from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (IDSA [Mermel 2009]; Tufariello 2020).
Empiric or pathogen-directed therapy for vancomycin-resistant enterococci (alternative agent) (off-label use): IV: 8 to 10 mg/kg once daily; 12 mg/kg once daily may be used for life-threatening infections with relatively high minimum inhibitory concentrations (MICs) (Britt 2017; Casapao 2013; Chuang 2017; Murray 2021; Nellore 2019). May be used as part of an appropriate combination regimen, especially in critically ill patients (Chuang 2018; Murray 2021; Sakoulas 2014). Treat uncomplicated bacteremia for 7 to 14 days from day of first negative blood culture, with longer courses warranted for endocarditis or metastatic sites of infection (IDSA [Mermel 2009]). Some experts recommend a duration of 5 to 7 days for uncomplicated infection with rapid blood culture clearance (within 24 hours) and in the absence of metastatic infection (Murray 2021).
Antibiotic lock technique (catheter-salvage strategy) (off-label use): Note: For infections caused by susceptible organisms when the catheter cannot be removed; use in addition to systemic antibiotics. Catheter salvage is not recommended for S. aureus (Bookstaver 2009; IDSA [Mermel 2009]).
Intracatheter: Prepare lock solution to final concentration of daptomycin 1 to 5 mg/mL; may be combined with heparin (Bookstaver 2009; Bookstaver 2013; Del Pozo 2012; Estes 2013; Justo 2014; Ortega 2014). Instill into each lumen of the catheter access port using a volume sufficient to fill the catheter (2 to 5 mL) with a dwell time of up to 72 hours, depending on frequency of catheter use (Girand 2019). Withdraw lock solution prior to catheter use; replace with fresh daptomycin lock solution after catheter use. Antibiotic lock therapy is given for the same duration as systemic antibiotics (Bookstaver 2009; IDSA [Mermel 2009]).
Cerebrospinal fluid shunt infection (alternative agent) (off-label use):
Pathogen-directed therapy for resistant pathogens (eg, staphylococci [including methicillin-resistant], Cutibacterium acnes, enterococci) or patients intolerant of other antibiotics: IV: 6 to 10 mg/kg once daily for 10 to 14 days; for staphylococci, usually used in combination with rifampin (eg, in the setting of retained hardware) (Antony 2012; IDSA [Tunkel 2017]).
Intraventricular (adjunct to systemic therapy; use a preservative-free preparation): 2 to 5 mg daily (Denetclaw 2014; IDSA [Tunkel 2017]; Mueller 2012). Additional intraventricular doses have been studied (Elvy 2008; Erritouni 2012). When intraventricular daptomycin is administered via a ventricular drain, clamp drain for 15 to 60 minutes after administration (allows solution to equilibrate in cerebrospinal fluid [CSF]) (IDSA [Tunkel 2017]). Note: Intraventricular administration is generally reserved for use in patients who fail parenteral therapy despite removal of CSF shunt or when CSF shunt cannot be removed (Baddour 2019).
Diabetic foot infection, moderate to severe (alternative agent) (off-label use):
Empiric or pathogen-directed therapy for methicillin-resistant S. aureus: IV: 4 to 6 mg/kg once daily. For empiric therapy, use as part of an appropriate combination regimen (Lipsky 2005; Weintrob 2020). If concomitant osteomyelitis is present, higher doses may be required (Malizos 2016). Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (IDSA [Lipsky 2012]; Weintrob 2020).
Endocarditis, treatment: Note: Daptomycin should not be used in patients with concomitant pneumonia (Silverman 2005).
Pathogen-directed therapy for methicillin-resistant staphylococci (native or prosthetic valve) (alternative agent): Note: Reserve use for patients who cannot receive vancomycin due to intolerance or elevated MIC (ESC [Habib 2015]; Karchmer 2020; Sexton 2020).
IV: 8 to 10 mg/kg once daily for ≥6 weeks. For patients with prosthetic valve endocarditis, use as part of an appropriate combination regimen (AHA [Baddour 2015]; ESC [Habib 2015]; IDSA [Liu 2011]; Karchmer 2020; Sexton 2020).
Pathogen-directed therapy for penicillin-, ampicillin-, and vancomycin-resistant enterococci (native or prosthetic valve) (off-label use): IV: 10 to 12 mg/kg once daily as part of an appropriate combination regimen for >6 weeks; may be used as monotherapy for native valve endocarditis (AHA [Baddour 2015]; Karchmer 2020; Sexton 2020).
Intracranial abscess (brain abscess, intracranial epidural abscess) or spinal epidural abscess (alternative agent) (off-label use):
Pathogen-directed therapy for staphylococci (including methicillin-resistant): IV: 6 to 10 mg/kg once daily; some experts usually give in combination with rifampin (Hasbun 2022; Sexton 2022a; Sexton 2022b; Southwick 2022). Duration usually ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Bodilsen 2018; Sexton 2022a; Sexton 2022b; Southwick 2022).
Meningitis, bacterial (alternative agent) (off-label use):
Pathogen-directed therapy for staphylococci (including methicillin-resistant): IV: 6 to 10 mg/kg once daily for 10 to 14 days; usually used in combination with rifampin (IDSA [Tunkel 2017]; Lee 2008; Tunkel 2019).
Osteomyelitis and/or discitis (alternative agent) (off-label use):
Pathogen-directed therapy for staphylococci (including methicillin-resistant): IV: 6 to 10 mg/kg once daily (IDSA [Berbari 2015]; Malizos 2016; Osmon 2019). Some experts combine with rifampin in the presence of retained hardware (IDSA [Berbari 2015]; IDSA [Liu 2011]).
Pathogen-directed therapy for enterococci (penicillin-susceptible or penicillin-resistant): IV: 6 to 10 mg/kg once daily (IDSA [Berbari 2015]; Osmon 2019).
Duration of therapy: Duration is generally ≥6 weeks. Shorter courses are appropriate if the affected bone is completely resected (eg, by amputation) (IDSA [Berbari 2015]; Osmon 2019).
Prosthetic joint infection (alternative agent) (off-label use):
Pathogen-directed therapy for staphylococci (including methicillin-resistant): IV: 6 to 10 mg/kg once daily. Duration ranges from 2 to 6 weeks depending on prosthesis management, use of rifampin, and other patient-specific factors (Berbari 2019; IDSA [Osmon 2013]). Note: In select cases (eg, debridement and retention of prosthesis or one-stage arthroplasty), combine with oral rifampin and give oral suppressive antibiotic therapy following completion of IV treatment (Berbari 2019; IDSA [Osmon 2013]).
Pathogen-directed therapy for enterococci (penicillin-susceptible or penicillin-resistant): IV: 6 to 10 mg/kg once daily for 4 to 6 weeks (Berbari 2019; IDSA [Osmon 2013]). Note: In select cases (eg, debridement and retention of prosthesis or one-stage arthroplasty), give oral suppressive antibiotic therapy following completion of IV treatment (Berbari 2019; IDSA [Osmon 2013]).
Septic arthritis (alternative agent) (off-label use):
Pathogen-directed therapy for staphylococci (including methicillin-resistant): IV: 6 mg/kg once daily (IDSA [Liu 2011]). If concomitant bacteremia is present, higher doses may be required (IDSA [Liu 2011]; Lowy 2022; Timbrook 2018). Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including oral step-down therapy (Goldenberg 2019; IDSA [Liu 2011]; Ross 2017); some experts recommend 4 weeks of parenteral therapy for patients with concomitant bacteremia (Goldenberg 2019).
Skin and skin structure infection (eg, erysipelas, cellulitis, necrotizing infections) (alternative agent): IV: 4 to 6 mg/kg once daily. Total duration of therapy is usually 5 to 14 days (including oral step-down therapy); for necrotizing infection, continue until further debridement is not necessary, patient has improved clinically, and patient is afebrile for ≥48 hours (IDSA [Stevens 2014]; Stevens 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV:
CrCl 30 to <130 mL/minute: No dosage adjustment necessary (Chaves 2014; expert opinion; manufacturer's labeling).
CrCl <30 mL/minute: Administer usual recommended dose every 48 hours (Chaves 2014; expert opinion; manufacturer's labeling). Note: High doses (>8 mg/kg) have not been well studied (Grégoire 2019; Tai 2018; Vlashyn 2021); monitor closely.
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Patients who are young (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).
IV: 10 mg/kg once daily (Falcone 2013b; Hobbs 2015; expert opinion); may increase to 12 mg/kg once daily for severe infections (eg, vancomycin-resistant Enterococcus bloodstream infection or endocarditis) (expert opinion).
Intermittent hemodialysis, thrice weekly: Dialyzable: 51.7% ± 9.2% removed by a standard hemodialysis session (Salama 2010):
Every-48-hour dosing (manufacturer's labeling): IV: Follow dosing recommendations for patients with CrCl <30 mL/minute (administer after hemodialysis on dialysis days).
Three times weekly (post dialysis) dosing: IV: Administer usual recommended dose (ie, 4 or 6 mg/kg) on 48-hour interdialytic days; increase dose by 50% after dialysis on the 72-hour interdialytic day (eg, if the dose is 6 mg/kg for a patient on a Monday, Wednesday, Friday dialysis schedule, administer 6 mg/kg after dialysis on Monday and Wednesday and on Friday administer 9 mg/kg after dialysis) (Butterfield 2013; Patel 2011). Doses ≥6 mg/kg (9 mg/kg on the 72-hour interdialytic day) have not been evaluated.
Note: Although IV administration as a 30-minute infusion or 2-minute IV push post dialysis is preferred (Haselden 2013), intradialytic administration (infused during the last hour of a 3.5-hour dialysis session) may be considered (Butterfield 2013).
Peritoneal dialysis: IV: Follow dosing recommendations for patients with CrCl <30 mL/minute (Benziger 2011; manufacturer's labeling).
CRRT:
Note: Daptomycin is cleared by CRRT, and its clearance is dependent on the effluent flow rate, filter type, and method of renal replacement (Breilh 2019; Churchwell 2006). Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), along with close monitoring for adverse effects (eg, increased CPK).
IV: 6 mg/kg every 24 hours (Corti 2013; Xie 2020).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), along with close monitoring for adverse effects (eg, increased CPK).
IV: Daily PIRRT (high-flux dialyzer; blood and dialysate flow rates of 160 mL/minute; duration 8 hours): 6 mg/kg every 24 hours to be given after PIRRT ends (Bogard 2011; Kielstein 2010; expert opinion).
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Generic: 350 mg (1 ea); 500 mg (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Cubicin: 500 mg (1 ea)
Cubicin RF: 500 mg (1 ea)
Generic: 350 mg (1 ea); 500 mg (1 ea)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Cubicin: 500 mg (1 ea)
Cubicin RF: 500 mg (1 ea)
Generic: 500 mg (1 ea)
Dapzura RT: FDA approved January 2022; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Dapzura RT contains sorbitol. Consult the prescribing information for additional information.
IV: Intermittent IV infusion:
Neonates: Infusion over 60 minutes has been reported in trials (Cohen-Wolkowiez 2012).
Infants <3 months: Infusion over 30 or 60 minutes has been reported in trials with every 12-hour dosing (Antachopoulos 2012; Cohen-Wolkowiez 2012).
Infants ≥3 months: Infusion over 30 minutes has been reported in trials; a longer infusion time of 60 minutes may be considered to minimize exposure to high peak serum concentration (Arrieta 2018; Bradley 2014).
Children 1 to 6 years: Infuse over 60 minutes.
Children ≥7 years and Adolescents: Infuse over 30 minutes.
Do not use in conjunction with ReadyMED elastomeric infusion pumps (Cardinal Health, Inc) due to an impurity (2-mercaptobenzothiazole) which leaches from the pump system into the daptomycin solution.
IV: Administer as an IV infusion over 30 minutes. May also administer IV push over 2 minutes. Do not use in conjunction with ReadyMED elastomeric infusion pumps (Cardinal Health, Inc) due to an impurity (2-mercaptobenzothiazole) leaching from the pump system into the daptomycin solution.
Intraventricular (off-label route): Use preservative-free preparations only. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow daptomycin solution to equilibrate in the cerebrospinal fluid (IDSA [Tunkel 2017]).
Cubicin: Store intact vials at 2°C to 8°C (36°F to 46°F); avoid excessive heat. Refer to manufacturer's labeling for specific storage instructions after reconstitution and/or dilution (varies by product and diluent). Extended storage information for reconstituted vial and diluted solution may be available; contact product manufacturer to obtain current recommendations.
Cubicin RF: Store intact vials at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Refer to manufacturer's labeling for specific storage instructions after reconstitution and/or dilution (varies by product and diluent).
Daptomycin 350 mg vial (Sagent): Store intact vials at 2°C to 8°C (36°F to 46°F); avoid excessive heat. Refer to manufacturer's labeling for specific storage instructions after reconstitution and/or dilution (varies by product and diluent).
Daptomycin 350 mg and 500 mg vial (Hospira): Store intact vials at 2°C to 25°C (36°F to 77°F); do not freeze. Brief exposure to 30°C (86°F) is permitted. Refer to manufacturer's labeling for specific storage instructions after reconstitution and/or dilution (varies by product and diluent).
Treatment of complicated skin and skin structure infections caused by susceptible Gram-positive bacteria (FDA approved in ages ≥1 year and adults); treatment of Staphylococcus aureus bacteremia (FDA approved in ages 1 to 17 years); treatment of S. aureus bacteremia, including right-sided infective endocarditis caused by methicillin-susceptible S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) (FDA approved in ages ≥18 years); has also been used for treatment of osteomyelitis. Note: Approved ages and uses for generic products may vary; consult labeling for specific information.
Cubicin may be confused with Cleocin, Cubicin RF
Cubicin RF may be confused with Cubicin
DAPTOmycin may be confused with DACTINomycin
Storage and preparations errors have occurred when Cubicin has been confused with Cubicin RF (ISMP 2016)
KIDs List: Daptomycin, when used in neonates and infants <1 year of age, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of neuromuscular and skeletal adverse events (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).
Antibiotics, including daptomycin, have been associated with Clostridioides difficile infection (CDI), including Clostridioides difficile associated diarrhea and Clostridioides difficile colitis; however, daptomycin is associated with a lower risk for CDI compared to other high-risk antibiotics (Ref). In addition, some data has suggested efficacy of daptomycin against C. difficile in vitro (Ref).
Mechanism: Non–dose-related; antibiotics disrupt the indigenous gut microbiota which promotes C. difficile spore germination, growth, and toxin production, leading to epithelial damage and colitis (Ref).
Onset: Varied; in general, antibiotic-associated CDI may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).
Risk factors: Antibiotics in general:
• Antibiotic exposure (highest risk factor); antibiotics most frequently associated with C. difficile include clindamycin, fluoroquinolones, third-/fourth-generation cephalosporins, and carbapenems (Ref)
• Long durations in a hospital or other health care setting (recent or current) (Ref)
• Older age (Ref)
• Immunocompromised conditions or serious underlying conditions (Ref)
• GI surgery/manipulation (Ref)
• Antiulcer medications, such as proton pump inhibitors and H2 blockers (suggested risk factor) (Ref)
• Chemotherapy (suggested risk factor) (Ref)
Daptomycin-induced eosinophilic pneumonitis (or eosinophilic interstitial pneumonia) has been reported. It is characterized by new-onset dyspnea, fever, bilateral infiltrates, and/or >25% eosinophils in bronchoalveolar lavage. Peripheral eosinophilia and fine crackles have also been commonly observed in case reports. Most cases reported improvement after daptomycin discontinuation; however, some patients developed chronic pneumonitis and required long-term corticosteroid treatment. However, literature does support a temporal association between daptomycin exposure and the development of eosinophilic pneumonia. Recurrence upon rechallenge has also been observed (Ref).
Mechanism: There have been several mechanisms suggested for daptomycin eosinophilic pneumonia with one centered on daptomycin accumulating and binding to pulmonary surfactant. This has been thought to cause direct or indirect damage to the pulmonary epithelium with resulting inflammation. Of note, one study found an association with development of eosinophilic pneumonia and cumulative dose or duration, while another study did not find this association. An allergic mechanism has also been suggested that attributes the pathophysiology to an antigen-mediated process in which alveolar macrophages and T-helper 2 (Th2) lymphocyte cells are activated, which then cause the subsequent release of interleukin-5, leading to an influx of eosinophils to the lungs (Ref).
Onset: Intermediate; usually 10 days to 4 weeks after initiation of therapy (Ref).
Risk factors: Note: Risk factors for this condition have not been well established (Ref)
• Males (potential risk factor) (Ref)
• Older age (potential risk factor) (Ref)
Immediate hypersensitivity reactions (urticaria, angioedema, anaphylaxis) have been reported (Ref). Delayed hypersensitivity reactions have also been reported, including skin rash, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) (Ref).
Mechanism: Non–dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria) are IgE-mediated. Delayed hypersensitivity reactions, including AGEP, are T-cell mediated (Ref).
Onset: Immediate hypersensitivity reactions: Rapid; generally occurs within 1 hour of administration, but may occur 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Varied; rashes usually begin 6 to 10 days after initiation. Severe cutaneous adverse reactions, including DRESS and AGEP, occur days to 8 weeks after drug exposure (Ref).
Daptomycin may cause symptomatic or asymptomatic increased creatine phosphokinase in blood specimen (CPK) (or creatine kinase) in pediatrics and adults. Use is also associated with significant CPK elevations (>10 times the upper limit of normal [ULN]) and skeletal muscle toxicities, such as myopathy and rhabdomyolysis (including cases of acute renal failure and/or liver injury secondary to the rhabdomyolysis). Case reports of daptomycin-induced rhabdomyolysis have occurred in the setting of monotherapy and with concomitant use of another medication, particularly an HMG CoA-reductase inhibitor (ie, a statin) (Ref). Daptomycin-induced CPK elevation is reversible upon discontinuation (Ref). Therapy discontinuation is warranted in patients with significant CPK elevations, which the prescribing information defines as an increase in CPK >5 times ULN (or 1,000 units/L) in patients with signs/symptoms of myopathy OR an increase in CPK ≥10 times ULN (or >2,000 units/L) in asymptomatic patients.
Mechanism: Exact mechanism is unknown, but it is believed that similar to daptomycin’s mechanism of action in bacterial cells that causes release of intracellular ions, it may also affect myocytes in skeletal muscles resulting in leakage of intracellular CPK (Ref).
Onset: Varied; in a case control study, the mean onset of CPK elevation was 16.7 days (range: 1 to 58 days), the mean onset for myopathy was 25 days (range: 3 to 176 days), and the mean onset for rhabdomyolysis was 13 days (range: 1 to 24 days) (Ref).
Risk factors: Note: A number of risk factors have been suggested, but overall data regarding risk factors are limited, unclear, and conflicting.
• Concomitant statin therapy (potential risk factor suggested by some observational studies (Ref); however, other observational studies have failed to find a significant association) (Ref)
• Obesity (BMI >25 kg/m2) (potential risk factor) (Ref) Note: Patients with obesity have lower daptomycin clearance potentially resulting in greater exposure (Ref)
• Critically ill patients/hypoxic conditions, such as severe sepsis (potential risk factor) (Ref)
• Daptomycin exposure:
- Dosing intervals more frequent than the recommended once-daily regimen (suggested by earlier phase, dose-finding human and animal studies where daptomycin was administered more frequently than once daily) (Ref)
- Trough levels ≥24.3 mg/L has been suggested as a potential risk factor increasing the risk of CPK elevations (Ref); however, other data have not found a significant association (Ref)
• Severe renal impairment (potential risk factor; conflicting evidence exists) (Ref)
Cases of peripheral neuropathy have been reported. There is also a single published case report of external popliteal sciatic nerve paralysis with daptomycin therapy (Ref). In addition, in a clinical trial evaluating daptomycin for bacteremia and endocarditis due to Staphylococcus aureus, an increased incidence of adverse events related to the peripheral nervous system (eg, paresthesia, dysesthesias, and peripheral neuropathies) were observed in patients receiving daptomycin compared to those receiving standard therapy; however, the authors described these events as mild to moderate, mostly short-lived, and resolving with continued treatment (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults and pediatric patients unless otherwise specified.
>10%: Gastrointestinal: Vomiting (children and adolescents: 3% to 11%)
1% to 10%:
Cardiovascular: Chest pain (adults: 7%), edema (adults: 7%), hypertension (adults: 6%), hypotension (adults: 2%)
Dermatologic: Diaphoresis (adults: 5%), pruritus (3% to 6%), skin rash (adults: 4%) (table 1)
Drug (Daptomycin) |
Comparator (Vancomycin or an Anti-Staphylococcal Semi-Synthetic Penicillin) |
Population |
Dose |
Indication |
Number of Patients (Daptomycin) |
Number of Patients (Vancomycin or an Anti-Staphylococcal Semi-Synthetic Penicillin) |
---|---|---|---|---|---|---|
4% |
4% |
Adults |
4 mg/kg |
Complicated skin and skin structure infections |
534 |
558 |
Gastrointestinal: Abdominal pain (adults: 6%; children and adolescents: 2%), diarrhea (5% to 7%)
Genitourinary: Urinary tract infection (adults: 2%)
Hepatic: Abnormal hepatic function tests (adults: 3%)
Infection: Bacteremia (adults: 5%), gram-negative organism infection (adults: 8%), sepsis (adults: 5%)
Nervous system: Dizziness (adults: 2%), headache (3% to 5%), insomnia (adults: 9%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (3% to 9%) (table 2)
Drug (Daptomycin) |
Comparator (Vancomycin, Clindamycin, Cefazolin, or an Anti-Staphylococcal Semi-Synthetic Penicillin) |
Population |
Dose |
Indication |
Number of Patients (Daptomycin) |
Number of Patients (Comparator) |
---|---|---|---|---|---|---|
7% |
0% |
Children and Adolescents |
Age specific dosing (7 mg/kg to 12 mg/kg) |
S. aureus bacteremia |
55 |
26 |
6% |
5% |
Children and Adolescents |
Age specific dosing (5 mg/kg to 10 mg/kg) |
Complicated skin and skin structure infections |
256 |
133 |
7% |
1% |
Adults |
6 mg/kg |
S. aureus bacteremia/endocarditis |
120 |
116 |
3% |
2% |
Adults |
4 mg/kg |
Complicated skin and skin structure infections |
534 |
558 |
Respiratory: Dyspnea (adults: 2%), pharyngolaryngeal pain (adults: 8%)
Miscellaneous: Fever (children and adolescents: 4%)
<1%:
Cardiovascular: Flushing, supraventricular cardiac arrhythmia
Dermatologic: Eczema
Endocrine & metabolic: Electrolyte disturbance, hypomagnesemia, increased lactate dehydrogenase, increased serum bicarbonate
Gastrointestinal: Abdominal distension, dysgeusia, stomatitis
Hematologic & oncologic: Eosinophilia, increased INR, leukocytosis, thrombocythemia, thrombocytopenia
Hepatic: Jaundice
Hypersensitivity: Hypersensitivity reaction
Nervous system: Fatigue, mental status changes, myasthenia, paresthesia, rigors, vertigo
Neuromuscular & skeletal: Arthralgia, asthenia, muscle cramps, myalgia
Ophthalmic: Eye irritation
Frequency not defined:
Cardiovascular: Atrial fibrillation, atrial flutter
Dermatologic: Vesicular eruption
Endocrine & metabolic: Increased serum phosphate
Gastrointestinal: Decreased appetite, epigastric distress, gingival pain, oral candidiasis, xerostomia
Genitourinary: Fungal urinary tract infection, proteinuria, vulvovaginal candidiasis
Hematologic & oncologic: Lymphadenopathy, prolonged prothrombin time
Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Infection: Candidiasis, fungal septicemia
Nervous system: Hallucination, hypoesthesia (oral)
Neuromuscular & skeletal: Dyskinesia
Ophthalmic: Blurred vision
Otic: Tinnitus
Renal: Renal insufficiency
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis (Gordon Spratt 2014), erythema of skin (Caulder 2014), Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria (Metz 2008), vesiculobullous dermatitis
Endocrine & metabolic: Hyperkalemia (Budovich 2014)
Gastrointestinal: Clostridioides difficile associated diarrhea (Webb 2020), dysphagia, nausea
Hematologic & oncologic: Anemia, myoglobin increased, neutropenia (Knoll 2013)
Hepatic: Hepatotoxicity (Abraham 2008)
Hypersensitivity: Anaphylaxis, angioedema (Gisler 2016)
Immunologic: Drug reaction with eosinophilia and systemic symptoms
Nervous system: Peripheral neuropathy (Villaverde Piñeiro 2018)
Neuromuscular & skeletal: Myopathy (Hagiya 2015), rhabdomyolysis (King 2014)
Ophthalmic: Visual disturbance
Renal: Acute interstitial nephritis (Bosak 2016), acute kidney injury (Abraham 2008)
Respiratory: Bronchiolitis obliterans organizing pneumonia, cough, eosinophilic pneumonitis (Higashi 2018)
Hypersensitivity to daptomycin or any component of the formulation
Concerns related to adverse effects:
• Eosinophilic pneumonia: Use may result in eosinophilic pneumonia; generally develops 2 to 4 weeks after therapy initiation. Monitor for signs and symptoms of eosinophilic pneumonia, including new onset or worsening fever, dyspnea, difficulty breathing, new infiltrates on chest imaging studies, and/or >25% eosinophils present in bronchoalveolar lavage. Discontinue use immediately with signs/symptoms of eosinophilic pneumonia and initiate appropriate treatment (ie, corticosteroids). May reoccur with re-exposure.
• Drug reaction with eosinophilia and systemic symptoms: Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported. Evaluate patients with symptoms of fever, peripheral eosinophilia, rash, and systemic organ impairment (eg, hepatic, pulmonary, renal); discontinue and institute appropriate treatment if DRESS is suspected.
• Hypersensitivity: Hypersensitivity reactions and anaphylaxis (including angioedema) have been reported with use. Discontinue use immediately with signs/symptoms of hypersensitivity and initiate appropriate treatment.
• Myopathy/rhabdomyolysis: May be associated with an increased incidence of myopathy; rhabdomyolysis, with or without acute renal failure, has also been reported. Discontinue in patients with signs and symptoms of myopathy in conjunction with an increase in CPK (>5 times ULN or 1,000 units/L) or in asymptomatic patients with a CPK ≥10 times ULN or >2,000 units/L. Myopathy may occur more frequently at dose and/or frequency in excess of recommended dosages. Consider temporarily interrupting therapy with other agents associated with rhabdomyolysis (eg, HMG-CoA reductase inhibitors) during daptomycin therapy.
• Peripheral neuropathy: Symptoms suggestive of peripheral neuropathy have been observed with treatment; monitor for new-onset or worsening neuropathy.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Tubulointerstitial nephritis: Tubulointerstitial nephritis (TIN) has been reported. Evaluate patients with new or worsening renal impairment; discontinue and institute appropriate treatment if TIN is suspected.
Disease-related concerns:
• Persisting or relapsing S. aureus bacteremia or endocarditis: Repeat blood cultures in patients with persisting or relapsing S. aureus bacteremia/endocarditis or poor clinical response. If culture is positive for S. aureus, perform minimum inhibitory concentration (MIC) susceptibility testing of the isolate and diagnostic evaluation of the patient to rule out sequestered foci of infection. Appropriate surgical intervention (eg, debridement, removal of prosthetic devices, valve replacement surgery) and/or consideration of a change in antibacterial therapy may be necessary.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required in severe renal impairment (CrCl <30 mL/minute). Limited data (eg, subgroup analysis) from cSSSI and endocarditis trials suggest possibly reduced clinical efficacy (relative to comparators) in patients with baseline moderate to severe renal impairment (<50 mL/minute).
Special populations:
• Pediatric: Avoid use in pediatric patients <12 months due to risk of potential muscular, neuromuscular, and/or nervous systems effects observed in neonatal canines.
Dosage form specific issues:
• Latex: Some products may contain latex.
Avoiding use in neonatal and pediatric patients <12 months is recommended in product labeling; neonatal animal models (canine) have shown reversible musculoskeletal, neuromuscular, and nervous system adverse effects including twitching, muscle rigidity of the limbs, and impaired use of the limbs; adverse effects were observed at lower serum concentrations than older canine models (approximately threefold less than juvenile models and ninefold less than adult models) and resolved within 28 days of discontinuation. The neuromuscular/skeletal adverse events occurred with canine doses and drug exposure levels that were higher than the standard adult human dose (6 mg/kg) and corresponding daptomycin exposure levels. Nervous system adverse effects are most associated with high peak serum concentrations; to mitigate this risk and lower patient's exposure, longer infusion times are used in pediatric patients (ie, age ≤6 years: Infuse over 60 minutes; >6 years of age: Infuse over 30 minutes vs adolescents ≥18 years: Bolus over 2 minutes) (Arrieta 2018). Evaluate risk vs benefit when considering use in neonates and infants.
None known.
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
HMG-CoA Reductase Inhibitors (Statins): May enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping statin (HMG-CoA reductase inhibitor) therapy prior to daptomycin. If daptomycin is used with a statin, creatine phosphokinase (CPK) monitoring could be considered. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methadone: May decrease the serum concentration of DAPTOmycin. Risk C: Monitor therapy
Simvastatin: May enhance the adverse/toxic effect of DAPTOmycin. Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Adverse events were not observed in animal reproduction studies. Successful use of daptomycin during the second and third trimesters of pregnancy has been described; however, only limited information is available from case reports.
Signs and symptoms of myopathy (muscle pain or weakness, particularly of the distal extremities), weekly CPK levels during therapy (more frequent monitoring if history of current or prior statin therapy and/or renal impairment), signs of peripheral neuropathy (new or worsening); observe for changes in bowel frequency; monitor renal function periodically; signs/symptoms of eosinophilic pneumonia.
Daptomycin binds to components of the cell membrane of susceptible organisms and causes rapid depolarization, inhibiting intracellular synthesis of DNA, RNA, and protein. Daptomycin is bactericidal in a concentration-dependent manner.
Distribution:
Vss:
Neonates and Infants <3 months of age: Median: 0.21 L/kg (range: 0.11 to 0.34 L/kg) (Cohen-Wolkowiez 2012).
Children 2 to 6 years of age: 0.14 L/kg (Abdel-Rahman 2008; Abdel-Rahman 2011).
Children 7 to 17 years of age: 0.11 ± 0.02 L/kg (Abdel-Rahman 2008).
Adults: 0.1 L/kg; Critically-ill patients: Vss: 0.23 ± 0.14 L/kg (Vilay 2011).
Bone (cancellous): fCmax (plasma)/fCmax (tissue) ratio, steady state: 75%; fAUCtissue/fAUCplasma ratio, steady state: 117% (Traunmüller 2010); bone/plasma ratio, single dose, ~7 hours postdose: ~8% to 10% (Montange 2014).
CSF:plasma ratio: AUC24 0.45%; Cmax 0.24% (Piva 2019).
Synovial fluid, single dose, ~7 hours postdose:plasma ratio ~54% (Montange 2014).
Protein binding: 90% to 93%; 84% to 88% in patients with CrCl <30 mL/minute.
Metabolism: Minor amounts of oxidative metabolites have been detected.
Half-life elimination:
Neonates and infants <3 months of age: Median: 6.2 hours (range: 3.7 to 9 hours) (Cohen-Wolkowiez 2012).
Children 2 to 6 years of age: Mean range: 5.3 to 5.7 hours (Abdel-Rahman 2008; Abdel-Rahman 2011).
Children 7 to 11 years of age: 5.6 ± 2.2 hours (Abdel-Rahman 2008).
Children 12 to 17 years of age: 6.7 ± 2.2 hours (Abdel-Rahman 2008).
Adults: 8 to 9 hours (up to 28 hours in renal impairment).
Excretion: Urine (78%; primarily as unchanged drug); feces (5.7%).
Clearance:
Neonates and infants <3 months of age: Median: 21 mL/hour/kg (range: 16 to 34 mL/hour/kg) (Cohen-Wolkowiez 2012).
Children 2 to 6 years of age: 19 to 20 mL/hour/kg (Abdel-Rahman 2008; Abdel-Rahman 2011).
Children 7 to 11 years of age: 17 mL/hour/kg (Abdel-Rahman 2008).
Children: 12 to 17 years of age: 11 mL/hour/kg (Abdel-Rahman 2008).
Adults: 8.3 to 9 mL/hour/kg.
Renal function impairment: Mean total plasma clearance was 9%, 22%, and 46% lower in patients with mild (CrCl 50 to 80 mL/minute), moderate (CrCl 30 to <50 mL/minute), and severe (CrCl <30 mL/minute) renal impairment, respectively, compared with those with healthy renal function. Mean AUC, half-life, and Vd at steady state increased with decreasing renal function.
Pediatric: In neonates and pediatric patients <12 years of age, clearance and volume of distribution are higher than older populations; these patients require higher mg/kg doses or more frequent dosing to achieve adequate serum concentrations and systemic exposure (Principi 2015)
Geriatric: Mean total clearance is reduced ~35% and AUC is increased ~58% in elderly patients compared with younger healthy subjects.
Obesity: Plasma clearance was 15% and 23% lower and AUC increased by 30% and 31% in moderately obese patients and extremely obese patients, respectively, compared with nonobese controls.
Anti-infective considerations:
Parameters associated with efficacy:
Gram-positive infection: Concentration dependent, associated with AUC24/minimum inhibitory concentration (MIC), goal: >400 (bacteriostatic), ≥666 (reduced mortality) (Falcone 2013a), >800 (bactericidal) (Di Paolo 2013), and fCmax (peak)/MIC, goal: 2.5 to 7 (bacteriostatic); 7 to 25 (2-log kill) (Safdar 2004).
Pathogen specific:
E. faecalis: fAUC24/MIC ≥7.2 (bacteriostatic) (Kidd 2018).
Enterococcus faecium: Cmax/MIC ≥0.14 to 0.25 (bacteriostatic); AUC24/MIC ≥0.94 to 1.67 (bacteriostatic) (Safdar 2004); fAUC24/MIC ≥0.85 (bacteriostatic); ≥12.9 (1-log kill) (Kidd 2018).
S. aureus: Cmax/MIC ≥59 to 94 (bacteriostatic); AUC24/MIC ≥388 to 537 (bacteriostatic) (Safdar 2004); fAUC24/MIC ≥42 to 43 (stasis) (Louie 2001; Safdar 2004).
Streptococcus pneumoniae: Cmax/MIC ≥12 to 36 (bacteriostatic); AUC24/MIC ≥75 to 237 (bacteriostatic) (Safdar 2004).
Expected drug exposure in patients with normal renal function:
AUC24:
Pediatric patients with bacteremia:
Children 2 to 6 years: 12 mg/kg once daily: 620 ± 109 mg•hour/L.
Children 7 to 11 years: 9 mg/kg once daily: 579 ± 116 mg•hour/L.
Children and Adolescents 12 to 17 years: 7 mg/kg once daily: 656 ± 334 mg•hour/L.
Adults (healthy):
6 mg/kg once daily: 632 ± 78 mg•hour/L.
8 mg/kg once daily: 858 ± 213 mg•hour/L.
10 mg/kg once daily: 1,039 ± 178 mg•hour/L.
12 mg/kg once daily: 1,277 ± 254 mg•hour/L.
Cmax (peak):
Pediatric patients with bacteremia:
Children 2 to 6 years: 12 mg/kg once daily: 106 ± 12.8 mg/L.
Children 7 to 11 years: 9 mg/kg once daily: 104 ± 14.5 mg/L.
Children and Adolescents 12 to 17 years: 7 mg/kg once daily: 104 ± 35.5 mg/L.
Adults (healthy):
6 mg/kg once daily: 93.9 ± 6 mg/L.
8 mg/kg once daily: 123.3 ± 16 mg/L.
10 mg/kg once daily: 141.1 ± 24 mg/L.
12 mg/kg once daily: 183.7 ± 25 mg/L.
Postantibiotic effect: Bacterial killing continues after daptomycin concentration falls below the MIC of targeted pathogen and varies based on the organism:
E. faecalis: 0.6 to 6.7 hours, dose dependent (Hanberger 1991).
S. aureus: 1 to 6.3 hours (Hanberger 1991; Pankuch 2003; Safdar 2004).
Methicillin-susceptible S. aureus: Mean: 2.4 hours (Pankuch 2003).
Methicillin-resistant S. aureus: Mean: 4.1 hours (Pankuch 2003).
S. pneumoniae: 1 to 2.5 hours (mean: 1.7 hours) (Pankuch 2003); postantibiotic effect of up to 10.8 hours has been observed at a dose of 10 mg/kg (Safdar 2004).
Parameters associated with toxicity: Cmin (trough) (steady state) ≥24.3 mg/L associated with increased risk of CPK elevation (Abdul-Aziz 2020; Bhavnani 2010).
Solution (reconstituted) (Cubicin Intravenous)
500 mg (per each): $534.59
Solution (reconstituted) (Cubicin RF Intravenous)
500 mg (per each): $534.59
Solution (reconstituted) (DAPTOmycin Intravenous)
350 mg (per each): $24.59 - $332.40
500 mg (per each): $23.04 - $534.58
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