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DAPTOmycin

Medically reviewed by Drugs.com. Last updated on Sep 5, 2020.

Pronunciation

(DAP toe mye sin)

Index Terms

  • Cidecin
  • Dapcin
  • LY146032

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

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)

Brand Names: U.S.

  • Cubicin
  • Cubicin RF

Pharmacologic Category

  • Antibiotic, Cyclic Lipopeptide

Pharmacology

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 post-dose: ~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).

Metabolism

Minor amounts of oxidative metabolites have been detected

Excretion

Urine (78%; primarily as unchanged drug); feces (5.7%)

Clearance:

Neonates and Infants <3 months: Median: 21 mL/hour/kg (range: 16 to 34 mL/hour/kg) (Cohen-Wolkowiez 2012)

Children 2 to 6 years: 19 to 20 mL/hour/kg (Abdel-Rahman 2008; Abdel-Rahman 2011)

Children 7 to 11 years: 17 mL/hour/kg (Abdel-Rahman 2008)

Children: 12 to 17 years: 11 mL/hour/kg (Abdel-Rahman 2008)

Adults: 8.3 to 9 mL/hour/kg

Half-Life Elimination

Neonates and Infants <3 months: Median: 6.2 hours (range: 3.7 to 9 hours) (Cohen-Wolkowiez 2012)

Children 2 to 6 years: Mean range: 5.3 to 5.7 hours (Abdel-Rahman 2008; Abdel-Rahman 2011)

Children 7 to 11 years: 5.6 ± 2.2 hours (Abdel-Rahman 2008)

Children 12 to 17 years: 6.7 ± 2.2 hours (Abdel-Rahman 2008)

Adults: 8 to 9 hours (up to 28 hours in renal impairment)

Protein Binding

90% to 93%; 84% to 88% in patients with CrCl <30 mL/minute

Special Populations: 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.

Special Populations: Elderly

Mean total clearance is reduced approximately 35% and AUC is increased approximately 58% in elderly patients compared with younger healthy subjects.

Special Populations: Children

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)

Special Populations Note

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), >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 (Bhavnani 2010).

Use: Labeled Indications

Bloodstream infection: Treatment of bloodstream infection caused by Staphylococcus aureus (methicillin-susceptible and methicillin-resistant isolates) in adults, including those with right-sided infective endocarditis; treatment of bloodstream infection due to S. aureus in pediatric patients 1 to 17 years of age.

Skin and skin structure infections, complicated: Treatment of complicated skin and skin structure infections caused by S. aureus (including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subspecies equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only) in adult and pediatric patients 1 to 17 years of age.

Limitations of use: Not indicated for the treatment of pneumonia.

Off Label Uses

Cerebrospinal fluid shunt infection

Based on the Infectious Diseases Society of America (IDSA) guidelines for healthcare-associated ventriculitis and meningitis, daptomycin is an effective and recommended alternative systemic therapy for treatment of healthcare-associated ventriculitis and meningitis caused by methicillin-resistant Staphylococcus aureus (MRSA), Cutibacterium acnes, or resistant enterococcal infections. Intraventricular administration of daptomycin, as an adjunct to systemic therapy, may be considered in patients with poor response to systemic antimicrobial therapy alone.

Diabetic foot infections

Data from a randomized, controlled trial support the use of daptomycin in the treatment of diabetic foot infections that are known or suspected to be caused by a gram-positive organism [Lipsky 2005].

Based on the IDSA guidelines for the diagnosis and treatment of diabetic foot infections, daptomycin is an effective and recommended alternative treatment option for moderate to severe diabetic foot infections (for MRSA coverage).

Endocarditis, treatment

Data from a limited number of patients studied suggest that daptomycin may be beneficial for the treatment of left-sided infective endocarditis (native or prosthetic valve) from gram-positive organisms, including methicillin-sensitive and methicillin-resistant S. aureus, Enterococcus faecalis, and vancomycin-resistant enterococci [Carugati 2013], [Das 2011], [Dohmen 2013], [Kaya 2013].

Based on the American Heart Association scientific statement on infective endocarditis in adults, daptomycin may be considered for treatment of left-sided infective endocarditis due to methicillin-sensitive and methicillin-resistant S. aureus (native valve) as an alternative to vancomycin therapy, and for treatment of endocarditis due to penicillin-, aminoglycoside-, and vancomycin-resistant enterococci (native or prosthetic valve).

Intracranial abscess (brain abscess, intracranial epidural abscess) or spinal epidural abscess

Clinical experience suggests the utility of daptomycin as an alternative agent for the treatment of intracranial abscess or spinal epidural abscess [Bodilsen 2018], [Sexton 2019a].

Meningitis, bacterial

Based on the IDSA guidelines for healthcare-associated ventriculitis and meningitis, daptomycin is an effective and recommended alternative systemic therapy for treatment of bacterial meningitis caused by staphylococci (including MRSA).

Osteomyelitis and/or discitis

Based on the IDSA guidelines for the treatment of MRSA infections in adults and children, daptomycin is an effective and recommended alternative to vancomycin for the treatment of bone and joint infections due to MRSA. Based on the IDSA guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, daptomycin is an effective and recommended alternative treatment option for native vertebral osteomyelitis due to staphylococci (including MRSA) and enterococci (penicillin-susceptible or penicillin-resistant).

Prosthetic joint infection

Based on the IDSA guidelines for the management of prosthetic joint infection, daptomycin is an effective and recommended agent for treatment of prosthetic joint infection with either staphylococci (oxacillin-susceptible or oxacillin-resistant) or enterococci (penicillin-susceptible or penicillin-resistant).

Septic arthritis

Based on the IDSA guidelines for the treatment of MRSA infections in adults and children, daptomycin is effective and recommended in the treatment of MRSA bone and joint infections, including septic arthritis.

Contraindications

Hypersensitivity to daptomycin or any component of the formulation

Dosing: Adult

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 2019; 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 2019; 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 2019). 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 2019).

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 MICs (Britt 2017; Casapao 2013; Chuang 2017; Murray 2020; Nellore 2019). May be used as part of an appropriate combination regimen, especially in critically ill patients (Chuang 2018; Murray 2020; 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]).

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 infections, 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 2019). 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 2019).

Endocarditis, treatment: Note: Daptomycin should not be used in patients with concomitant pneumonia (Silverman 2005).

Pathogen-directed therapy for methicillin-resistant staphylococci (native valve) (alternative agent): IV: 8 to 10 mg/kg once daily for 6 weeks (AHA [Baddour 2015]; ESC [Habib 2015]; IDSA [Liu 2011]; Sexton 2019c).

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 2019; Sexton 2019c).

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; 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 2019a; Sexton 2019b; Southwick 2020).

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 2019; 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 2020).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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.

Dosing: Obesity

The recommendations for dosing in obese patients are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.

Note: Higher weight-based dosing (8 to 12 mg/kg) has been recommended in select populations (eg, methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, vancomycin-resistant enterococci bacteremia, sepsis) due to the pharmacokinetic variability observed and potential benefit with higher AUCs (Britt 2017; Falcone 2013; Safdar 2004). However, while higher dosing will result in higher overall AUCs, this may lead to more adverse reactions (eg, elevated CPK, myalgias).

Manufacturers labeling and some clinical data recommend the use of total body weight (TBW) for weight-based dosing in obese patients (Dvorchik 2005); however, in obese patients, TBW dosing yields significant increases in AUC and Cmax (Dvorchik 2005; Pai 2007) and a higher incidence of adverse reactions (eg, CPK elevation) (Bhavnani 2010; Bookstaver 2013) and should not be used in this population (Pai 2007). Some experts recommend fixed (non-weight based) dosing based on Monte Carlo simulations to achieve comparable probabilities of target attainment; however, this strategy has not been validated prospectively to determine clinical outcomes (Butterfield-Cowper 2018; Falcone 2013; Lorenzo 2020).

Recommended dosing:

Adjusted body weight: Note: One retrospective equivalency study suggests no difference in clinical failure rate in patients with class I, II, or III obesity using adjusted body weight vs TBW (Fox 2019).

IV: Clinical expert opinion recommends using adjusted body weight in obese patients (≥30 kg/m2). Adjusted body weight can be calculated by using the following equation: Adjusted body weight = (ideal body weight [IBW] + 0.4 [TBW – IBW]).

Reconstitution

IV:

Cubicin: Reconstitute vial with 10 mL NS to a concentration of 50 mg/mL. Add NS to vial and rotate gently to wet powder. Allow to stand for 10 minutes, then gently swirl to obtain completely reconstituted solution. Do not shake or agitate vial vigorously. For administration via IVPB, further dilute in 50 mL NS prior to administration.

Cubicin RF: Reconstitute vial with 10 mL SWFI or bacteriostatic water for injection to a concentration of 50 mg/mL; do not use saline based diluents (will result in hyperosmotic solution that may cause infusion site reactions when administered as an IV injection over 2 minutes). Add diluent to vial and rotate or swirl for a few minutes, as needed, to obtain a completely reconstituted solution. For administration via IVPB, further dilute in 50 mL NS prior to administration.

Daptomycin 350 mg vial: Reconstitute vial with 7 mL NS to a concentration of 50 mg/mL. Add NS to vial and rotate gently to wet powder. Allow to stand for 10 minutes, then gently swirl to obtain completely reconstituted solution. Do not shake or agitate vial vigorously. For administration via IVPB, further dilute in 50 mL NS prior to administration.

Administration

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]).

Storage

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: 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).

Drug Interactions

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 HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Consider therapy modification

Simvastatin: May enhance the adverse/toxic effect of DAPTOmycin. Avoid combination

Test Interactions

Daptomycin may cause false prolongation of the PT and increase of INR with certain recombinant thromboplastin reagents. This appears to be a dose-dependent phenomenon. If PT/INR is elevated, repeat PT/INR immediately prior to next daptomycin dose (eg, trough). If PT/INR remains elevated, repeat PT/INR using alternate reagents (if available) and evaluate for other causes of elevated PT/INR.

Adverse Reactions

1% to 10%:

Cardiovascular: Chest pain (adults: 7%), edema (adults: 7%), hypertension (adults: 6%), hypotension (adults: 2%)

Central nervous system: Insomnia (adults: 9%), headache (3% to 5%), dizziness (adults: 2%)

Dermatologic: Pruritus (3% to 6%), diaphoresis (adults: 5%), skin rash (adults: 4%)

Gastrointestinal: Diarrhea (5% to 7%), abdominal pain (adults: 6%; children and adolescents: 2%), vomiting (children and adolescents: 3% to 11%; adults: <1%)

Genitourinary: Urinary tract infection (adults: 2%)

Hepatic: Abnormal hepatic function tests (adults: 3%), increased serum alkaline phosphatase (adults: 2%)

Infection: Gram-negative organism infection (adults: 8%), bacteremia (adults: 5%), sepsis (adults: 5%)

Neuromuscular & skeletal: Increased creatine phosphokinase (3% to 9%)

Respiratory: Pharyngolaryngeal pain (adults: 8%), dyspnea (adults: 2%)

Miscellaneous: Fever (≤4%)

Frequency not defined:

Cardiovascular: Atrial fibrillation, atrial flutter

Central nervous system: Hallucination, hypoesthesia (including oral)

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

Hepatic: Increased serum ALT, increased serum AST

Infection: Candidiasis, fungal septicemia

Neuromuscular & skeletal: Dyskinesia

Ophthalmic: Blurred vision

Otic: Tinnitus

Renal: Renal insufficiency

<1%, postmarketing, and/or case reports: Abdominal distension, acute generalized exanthematous pustulosis, acute renal failure, anaphylaxis, anemia, arthralgia, bronchiolitis obliterans organizing pneumonia, Clostridioides (formerly Clostridium) difficile-associated diarrhea, cough, decreased appetite, dysgeusia, eczema, electrolyte disturbance, eosinophilia, eosinophilic pneumonitis, eye irritation, fatigue, flushing, hypomagnesemia, hypersensitivity reaction (including angioedema, drug rash with eosinophilia and systemic symptoms [DRESS], dysphagia, hives, pulmonary eosinophilia, truncal erythema), increased lactate dehydrogenase, increased myoglobin, increased serum bicarbonate, jaundice, leukocytosis, mental status changes, muscle cramps, myalgia, myasthenia, myopathy, nausea, neutropenia (Knoll 2013), paresthesia, peripheral neuropathy, renal failure, rhabdomyolysis, rigors, Stevens-Johnson syndrome, stomatitis, supraventricular cardiac arrhythmia, thrombocythemia, thrombocytopenia, vertigo, vesiculobullous dermatitis, visual disturbance, weakness

Warnings/Precautions

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.

Monitoring Parameters

Monitor signs and symptoms of infection. CPK should be monitored at least weekly during therapy; more frequent monitoring if current or prior statin therapy, unexplained CPK increases, and/or renal impairment. Monitor for muscle pain or weakness, especially if noted in distal extremities. Monitor for new onset or worsening peripheral neuropathy. Monitor for signs/symptoms of eosinophilic pneumonia.

Pregnancy Considerations

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.

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Abdominal pain

• Trouble sleeping

• Sweating a lot

• Vomiting

• Sore throat

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Severe headache

• Severe dizziness

• Passing out

• Vision changes

• Severe loss of strength and energy

• Burning or numbness feeling

• Muscle pain

• Muscle weakness

• Dark urine

• Not able to pass urine

• Cough

• Shortness of breath

• Chest pain

• Swelling

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.