Skip to Content

DAPTOmycin

Pronunciation

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: 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: Median: 0.21 L/kg (range: 0.11 to 0.34 L/kg) (Cohen-Wolkowiez 2012)

Children 2 to 6 years: 0.14 L/kg (Abdel-Rahman 2008; Abdel-Rahman 2011)

Children 7 to 17 years: 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)

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.

Use: Labeled Indications

Skin and skin structure infections, complicated: Treatment of complicated skin and skin structure infections caused by Staphylococcus 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.

S. aureus bacteremia: Treatment of S. aureus (methicillin-susceptible and methicillin-resistant isolates) bacteremia in adults, including those with right-sided infective endocarditis.

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

Off Label Uses

Diabetic foot infections

Data from a randomized, controlled trial supports 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]. Additional data may be necessary to further define the role of daptomycin for this condition.

Based on the Infectious Diseases Society of America (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 methicillin-resistant Staphylococcus aureus coverage).

Infective endocarditis (due to S. aureus [left-sided] or Enterococcus), treatment (adults)

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 Enterococcus [Carugati 2013], [Das 2011], [Dohmen 2013], [Kaya 2013]. Additional data may be necessary to further define the role of daptomycin in this condition.

Based on the American Heart Association (AHA) Scientific Statement for 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 Enterococcus spp (native or prosthetic valve).

Osteomyelitis and/or septic arthritis due to methicillin-resistant Staphylococcus aureus

Based on the Infectious Diseases Society of America (IDSA) guidelines for the Diagnosis and Treatment of Methicillin-Resistant Infectious Diseases Society of America (IDSA) guidelines for the Diagnosis and Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in Adults and Children (MRSA) Infections in Adults and Children, daptomycin is a recommended alternative to vancomycin for the treatment of bone and joint infections due to MRSA.

Osteomyelitis, native vertebral

Based on the Infectious Diseases Society of America (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 (oxacillin-susceptible or -resistant) or Enterococcus spp. (penicillin-resistant or –sensitive).

Prosthetic joint infection caused by staphylococci (oxacillin-susceptible or -resistant) or Enterococcus (penicillin-susceptible or -resistant)

Based on the Infectious Diseases Society of America (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 -resistant) or Enterococcus (penicillin-susceptible or -resistant).

Vancomycin-resistant enterococci (VRE) bacteremia

Data from a retrospective cohort study suggest that daptomycin may be beneficial for the treatment of VRE bacteremia [Britt 2015]. Additional trials may be necessary to further define the role of daptomycin in this condition.

Contraindications

Hypersensitivity to daptomycin or any component of the formulation

Dosing: Adult

Diabetic foot infections without osteomyelitis (off-label use): IV: 4 mg/kg once daily (Lipsky 2005)

Infective endocarditis, treatment: IV:

S. aureus (right-sided, native valve): Note: Clinical trial demonstrating noninferiority to standard therapy for S. aureus right-sided endocarditis included only patients with native valve infective endocarditis (Fowler 2006)

Manufacturer labeling: 6 mg/kg once daily for 2 to 6 weeks

Alternate recommendation: 8 to 10 mg/kg once daily (IDSA [Liu 2011])

S. aureus (left-sided, native valve) (off-label use): ≥8 mg/kg once daily for 6 weeks, consultation with infectious disease specialist recommended for dosage selection (AHA [Baddour 2015])

Enterococcus (penicillin-, aminoglycoside-, and vancomycin-resistant) (off-label use): 10 to 12 mg/kg once daily for a minimum of 6 weeks; combination therapy with ampicillin, ceftaroline, or another antibiotic may be considered in patients with persistent bacteremia or strains with relatively high MICs to daptomycin within the susceptible range (<4 mcg/mL) (AHA [Baddour 2015])

Osteomyelitis due to MRSA (off-label use): IV: 6 mg/kg once daily for a minimum of 8 weeks; some experts combine with rifampin (in patients with concurrent bacteremia, initiate rifampin after clearance of bacteremia) (IDSA [Liu 2011])

Osteomyelitis, native vertebral (off-label use) (IDSA [Berbari 2015]): IV:

Staphylococci (oxacillin-susceptible or -resistant): 6 to 8 mg/kg once daily for 6 weeks

Enterococcus spp (penicillin-susceptible or -resistant): 6 mg/kg once daily for 6 weeks. Note: In patients with infective endocarditis, the addition of an aminoglycoside for 4 to 6 weeks is recommended

Prosthetic joint infection (off-label use): IV:

Enterococcus spp (penicillin-susceptible or -resistant) (alternative treatment): 6 mg/kg every 24 hours for 4 to 6 weeks (consider adding an aminoglycoside), followed by an oral antibiotic suppressive regimen if a debridement and retention strategy or 1-stage exchange is chosen (Osmon 2013)

Staphylococci (oxacillin-susceptible or -resistant) (alternative treatment): 6 mg/kg every 24 hours for 2 to 6 weeks (used in combination with rifampin if a debridement and retention strategy or 1-stage exchange is chosen), followed by oral antibiotic treatment (and suppressive regimen if a debridement and retention strategy or 1-stage exchange is chosen) (Osmon 2013)

S. aureus bacteremia: IV

Manufacturer labeling: 6 mg/kg once daily for 2 to 6 weeks

Alternate recommendation: 8 to 10 mg/kg once daily for complicated bacteremia (IDSA [Liu 2011])

Septic arthritis due to MRSA (off-label use): IV: 6 mg/kg once daily for 3 to 4 weeks (IDSA [Liu 2011])

Skin and skin structure infections, complicated: IV: 4 mg/kg once daily for 7 to 14 days

VRE bacteremia (off-label use): IV: 6 to 8 mg/kg once daily (Casapao 2013; Gallagher 2009); however, based on pharmacokinetic data, higher doses (up to 12 mg/kg once daily) may be appropriate for difficult to treat infections (Benvenuto 2006). Additional trials may be necessary to further define the role of daptomycin in this condition.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Skin and skin structure infections, complicated: Children and Adolescents: IV:

1 to <2 years: 10 mg/kg once daily

2 to 6 years: 9 mg/kg once daily

7 to 11 years: 7 mg/kg once daily

12 to 17 years: 5 mg/kg once daily

≥18 years: Refer to adult dosing

Duration of therapy: ≤14 days

Dosing: Renal Impairment

Adults:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute:

Skin and soft tissue infections: 4 mg/kg every 48 hours

Staphylococcal bacteremia: 6 mg/kg every 48 hours

End-stage renal disease (ESRD) on intermittent hemodialysis (IHD): Note: Hemodialysis: Dialyzable: 15% (removed by 4-hour hemodialysis session); 50% (removed by 4-hour high permeability intermittent hemodialysis session) (Salama 2010). A notable amount of drug may be removed in the last 30 minutes of dialysis; administration after dialysis is completed is preferred (Haselden 2013).

Manufacturer's labeling: Dose as in CrCl <30 mL/minute (administer after hemodialysis on dialysis days).

Alternate dosing: Administer usual recommended dose (ie, 4 or 6 mg/kg) on 48 hour intradialytic days; increase dose by 50% after dialysis on the 72 hour intradialytic 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) (Haselden 2013, Patel 2011).

Peritoneal dialysis (PD): Dose as in CrCl <30 mL/minute

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

Continuous veno-venous hemodialysis (CVVHD): 8 mg/kg every 48 hours (Vilay 2010)

Note: For other forms of CRRT (eg, CVVH or CVVHDF), dosing as with CrCl <30 mL/minute may result in low Cmax. May consider 4 to 6 mg/kg every 24 hours (or 8 mg/kg every 48 hours) depending on site or severity of infection or if not responding to standard dosing; therapeutic drug monitoring and/or more frequent serum CPK levels may be necessary (Heintz 2009).

Slow extended daily dialysis (or extended dialysis): 6 mg/kg every 24 hours (Kielstein 2010); Note: Dialysis should be initiated within 8 hours of administering daptomycin dose to avoid dose accumulation.

Children and Adolescents: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Dosing: Hepatic Impairment

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).

Reconstitution

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 25 mL (children 1 to 6 years of age) or 50 mL (children and adolescents 7 to 17 years and adults) 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 25 mL (children 1 to 6 years of age) or 50 mL (children and adolescents 7 to 17 years and adults) NS prior to administration.

Administration

Administer as an IV infusion over 30 minutes (children and adolescents 7 to 17 years of age and adults) or 60 minutes (children 1 to 6 years of age). May also administer IV push over 2 minutes in adults only; do not administer IV push to pediatric patients. 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.

Compatibility

See Trissel’s IV Compatibility Database

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).

Drug Interactions

HMG-CoA Reductase Inhibitors: 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

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 (≤3%)

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, 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.

• Hypersensitivity: Hypersensitivity reactions and anaphylaxis (including angioedema, and drug rash with eosinophilia and systemic symptoms [DRESS]) 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.

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).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, abdominal pain, insomnia, sweating a lot, or pharyngitis. Have patient report immediately to prescriber severe headache, dizziness, passing out, vision changes, severe loss of strength and energy, burning or numbness feeling, muscle pain, muscle weakness, dark urine, urinary retention, change in amount of urine passed, cough, shortness of breath, angina, edema, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Hide