NDC 0143-9378 Daptomycin

Daptomycin

NDC Product Code 0143-9378

NDC 0143-9378-01

Package Description: 1 VIAL, SINGLE-DOSE in 1 CARTON > 10 mL in 1 VIAL, SINGLE-DOSE

NDC Product Information

Daptomycin with NDC 0143-9378 is a a human prescription drug product labeled by Hikma Pharmaceuticals Usa Inc.. The generic name of Daptomycin is daptomycin. The product's dosage form is injection, powder, lyophilized, for solution and is administered via intravenous form.

Labeler Name: Hikma Pharmaceuticals Usa Inc.

Dosage Form: Injection, Powder, Lyophilized, For Solution - A dosage form intended for the solution prepared by lyophilization ("freeze drying"), a process which involves the removal of water from products in the frozen state at extremely low pressures; this is intended for subsequent addition of liquid to create a solution that conforms in all respects to the requirements for Injections.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Daptomycin Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • DAPTOMYCIN 500 mg/10mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SODIUM HYDROXIDE (UNII: 55X04QC32I)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intravenous - Administration within or into a vein or veins.
  • Intravenous - Administration within or into a vein or veins.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Lipopeptide Antibacterial - [EPC] (Established Pharmacologic Class)
  • Lipopeptides - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Hikma Pharmaceuticals Usa Inc.
Labeler Code: 0143
FDA Application Number: ANDA212022 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 01-01-2020 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Daptomycin Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1.1 Complicated Skin And Skin Structure Infections (Csssi)

Daptomycin for Injection is indicated for the treatment of adult patients with complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive bacteria:


Staphylococcus aureus (including methicillin-resistant isolates),


Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp.


equisimilis, and


Enterococcus faecalis (vancomycin-susceptible isolates only).


Pediatric use information is approved for Merck & Co., Inc.’s Cubicin (daptomycin for injection). However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

1.2 Staphylococcus Aureus Bloodstream Infections (Bacteremia) In Adult Patients, Including Those With Right-Sided Infective Endocarditis, Caused By Methicillin-Susceptible And Methicillin-Resistant Isolates

Daptomycin for Injection is indicated for the treatment of adult patients with


Staphylococcus aureus bloodstream infections (bacteremia), including adult patients with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates.


Pediatric use information is approved for Merck & Co., Inc.’s Cubicin (daptomycin for injection). However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

1.4 Limitations Of Use

Daptomycin for Injection is not indicated for the treatment of pneumonia.Daptomycin for Injection is not indicated for the treatment of pneumonia.Daptomycin for Injection is not indicated for the treatment of left-sided infective endocarditis due to


S. aureus. The clinical trial of Daptomycin for Injection in adult patients with


S. aureus bloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor


[see


Clinical Studies (14.2)].


 Daptomycin for Injection has not been studied in patients with prosthetic valve endocarditis.


Daptomycin for Injection is not recommended in pediatric patients younger than 1 year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs


[see


Warnings and Precautions (5.5) and


Nonclinical Toxicology (13.2)]


.

1.5 Usage

Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to daptomycin.To reduce the development of drug-resistant bacteria and maintain the effectiveness of Daptomycin for Injection and other antibacterial drugs, Daptomycin for Injection should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.When culture and susceptibility information is available, it should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Empiric therapy may be initiated while awaiting test results.

2.2 Dosage In Adults For Csssi

Administer daptomycin for injection 4 mg/kg to adult patients intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days.Pediatric use information is approved for Merck & Co., Inc.’s Cubicin (daptomycin for injection). However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.4 Dosage In Adult Patients With Staphylococcus Aureus Bloodstream Infections (Bacteremia), Including Those With Right-Sided Infective Endocarditis, Caused By Methicillin-Susceptible And Methicillin-Resistant Isolates

Administer daptomycin for injection 6 mg/kg to adult patients intravenously in 0.9% sodium chloride injection once every 24 hours for 2 to 6 weeks. There are limited safety data for the use of daptomycin for injection for more than 28 days of therapy. In the Phase 3 trial, there were a total of 14 adult patients who were treated with daptomycin for injection for more than 28 days.Pediatric use information is approved for Merck & Co., Inc.’s Cubicin (daptomycin for injection). However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.7 Preparation And Administration Of Daptomycin For Injection

There are two formulations of daptomycin that have differences concerning storage and reconstitution. Carefully follow the reconstitution and storage procedures in labeling.

2.8 Compatible Intravenous Solutions

Daptomycin for injection is compatible with 0.9% sodium chloride injection and lactated Ringer's injection.

2.9 Incompatibilities

Daptomycin for injection is not compatible with dextrose-containing diluents.Daptomycin for injection should not be used in conjunction with ReadyMED


® elastomeric infusion pumps. Stability studies of daptomycin for injection solutions stored in ReadyMED


® elastomeric infusion pumps identified an impurity (2-mercaptobenzothiazole) leaching from this pump system into the daptomycin for injection solution.


Because only limited data are available on the compatibility of daptomycin for injectionwith other IV substances, additives and other medications should not be added to daptomycin for injection single-dose vials or infusion bags, or infused simultaneously with daptomycin for injection through the same IV line. If the same IV line is used for sequential infusion of different drugs, the line should be flushed with a compatible intravenous solution before and after infusion with daptomycin for injection.

3 Dosage Forms And Strengths

For Injection: 500 mg daptomycin as a sterile, pale yellow to light brown lyophilized powder for reconstitution in a single-dose vial.

4 Contraindications

Daptomycin for Injection is contraindicated in patients with known hypersensitivity to daptomycin.

5.1 Anaphylaxis/Hypersensitivity Reactions

Anaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including daptomycin, and may be life-threatening. If an allergic reaction to daptomycin occurs, discontinue the drug and institute appropriate therapy


[see


Adverse Reactions (6.2)].

5.2 Myopathy And Rhabdomyolysis

Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in creatine phosphokinase (CPK) values to greater than 10 times the upper limit of normal (ULN), has been reported with the use of daptomycin. Rhabdomyolysis, with or without acute renal failure, has been reported


[see


Adverse Reactions (6.2)]


.


Patients receiving daptomycin should be monitored for the development of muscle pain or weakness, particularly of the distal extremities. In patients who receive daptomycin, CPK levels should be monitored weekly, and more frequently in patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment with daptomycin.In adult patients with renal impairment, both renal function and CPK should be monitored more frequently than once weekly


[see


Use in Specific Populations (8.6) and


Clinical Pharmacology (12.3)].


In Phase 1 studies and Phase 2 clinical trials in adults, CPK elevations appeared to be more frequent when daptomycin was dosed more than once daily. Therefore, daptomycin should not be dosed more frequently than once a day.Daptomycin should be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to levels >1,000 U/L (~5× ULN), and in patients without reported symptoms who have marked elevations in CPK, with levels >2,000 U/L (≥10× ULN). In addition, consideration should be given to suspending agents associated with rhabdomyolysis, such as HMG-CoA reductase inhibitors, temporarily in patients receiving daptomycin 


[see


Drug Interactions (7.1)].

5.3 Eosinophilic Pneumonia

Eosinophilic pneumonia has been reported in patients receiving daptomycin 


[see


Adverse Reactions (6.2)].


In reported cases associated with daptomycin, patients developed fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates or organizing pneumonia. In general, patients developed eosinophilic pneumonia 2 to 4 weeks after starting daptomycin and improved when daptomycin was discontinued and steroid therapy was initiated. Recurrence of eosinophilic pneumonia upon re-exposure has been reported. Patients who develop these signs and symptoms while receiving daptomycin should undergo prompt medical evaluation, and daptomycin should be discontinued immediately. Treatment with systemic steroids is recommended.

5.4 Peripheral Neuropathy

Cases of peripheral neuropathy have been reported during the daptomycin postmarketing experience


[see


Adverse Reactions (6.2)].


Therefore, physicians should be alert to signs and symptoms of peripheral neuropathy in patients receiving daptomycin. Monitor for neuropathy and consider discontinuation.

5.5 Potential Nervous System And/Or Muscular System Effects In Pediatric Patients Younger Than 12 Months

Avoid use of daptomycin in pediatric patients younger than 12 months due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs with intravenous daptomycin


[see


Nonclinical Toxicology (13.2)].

5.6 Clostridium Difficile-Associated Diarrhea

Clostridium difficile–associated diarrhea (CDAD) has been reported with the use of nearly all systemic antibacterial agents, including daptomycin, and may range in severity from mild diarrhea to fatal colitis


[see


Adverse Reactions (6.2)].


Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of


C. difficile.


C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of


C. difficile cause increased morbidity and mortality, since these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.


If CDAD is suspected or confirmed, ongoing antibacterial use not directed against


C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of


C. difficile, and surgical evaluation should be instituted as clinically indicated.

5.7 Persisting Or Relapsing S. Aureus Bacteremia/Endocarditis

Patients with persisting or relapsing


S. aureus bacteremia/endocarditis or poor clinical response should have repeat blood cultures. If a blood culture is positive for


S. aureus, minimum inhibitory concentration (MIC) susceptibility testing of the isolate should be performed using a standardized procedure, and diagnostic evaluation of the patient should be performed to rule out sequestered foci of infection. Appropriate surgical intervention (e.g., debridement, removal of prosthetic devices, valve replacement surgery) and/or consideration of a change in antibacterial regimen may be required.


Failure of treatment due to persisting or relapsing


S. aureus bacteremia/endocarditis may be due to reduced daptomycin susceptibility (as evidenced by increasing MIC of the


S. aureus isolate)


[see


Clinical Studies (14.2)].

5.8 Decreased Efficacy In Patients With Moderate Baseline Renal Impairment

Limited data are available from the two Phase 3 complicated skin and skin structure infection (cSSSI) trials regarding clinical efficacy of daptomycin treatment in adult patients with creatinine clearance (CL


CR) <50 mL/min; only 31/534 (6%) patients treated with daptomycin in the intent-to-treat (ITT) population had a baseline CL


CR <50 mL/min. Table 4 shows the number of adult patients by renal function and treatment group who were clinical successes in the Phase 3 cSSSI trials.


Table 4: Clinical Success Rates by Renal Function and Treatment Group in Phase 3 cSSSI Trials in Adult Patients (Population: ITT) CL


CR Success Rate


n/N (%)


Daptomycin


4 mg/kg q24h


Comparator50-70 mL/min25/38 (66%)30/48 (63%)30-<50 mL/min7/15 (47%)20/35 (57%)In a subgroup analysis of the ITT population in the Phase 3


S. aureus bacteremia/endocarditis trial, clinical success rates, as determined by a treatment-blinded Adjudication Committee


[see


Clinical Studies (14.2)]


, in the daptomycin-treated adult patients were lower in patients with baseline CL


CR <50 mL/min (see


Table 5). A decrease of the magnitude shown in Table 5 was not observed in comparator-treated patients.


Table 5: Adjudication Committee Clinical Success Rates at Test of Cure by Baseline Creatinine Clearance and Treatment Subgroup in the S. aureus Bacteremia/Endocarditis Trial in Adult Patients (Population: ITT) Baseline CL


CR Success Rate


n/N (%)


Daptomycin


6 mg/kg q24h


Comparator Bacteremia Right-Sided Infective Endocarditis Bacteremia Right-Sided Infective Endocarditis>80 mL/min30/50 (60%)7/14 (50%)19/42 (45%)5/11 (46%)50–80 mL/min12/26 (46%)1/4 (25%)13/31 (42%)1/2 (50%)30–<50 mL/min2/14 (14%)0/1 (0%)7/17 (41%)1/1 (100%)Consider these data when selecting antibacterial therapy for use in adult patients with baseline moderate to severe renal impairment.

5.9 Drug-Laboratory Test Interactions

Clinically relevant plasma concentrations of daptomycin have been observed to cause a significant concentration-dependent false prolongation of prothrombin time (PT) and elevation of International Normalized Ratio (INR) when certain recombinant thromboplastin reagents are utilized for the assay


[see


Drug Interactions (7.2)]


.

5.10 Non-Susceptible Microorganisms

The use of antibacterials may promote the overgrowth of non-susceptible microorganisms. If these infections occur during therapy, appropriate measures should be taken.Prescribing daptomycin in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

6 Adverse Reactions

  • The following adverse reactions are described, or described in greater detail, in other sections:Anaphylaxis/hypersensitivity reactions
  • [see
  • Warnings and Precautions (5.1)]
  • Myopathy and rhabdomyolysis
  • [see
  • Warnings and Precautions (5.2)]
  • Eosinophilic pneumonia
  • [see
  • Warnings and Precautions (5.3)]
  • Peripheral neuropathy
  • [see
  • Warnings and Precautions (5.4)]
  • Increased International Normalized Ratio (INR)/prolonged prothrombin time
  • [see
  • Warnings and Precautions (5.9) and
  • Drug Interactions (7.2)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

6.2 Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of daptomycin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Blood and lymphatic system disorders: anemia, thrombocytopenia


General and administration site conditions: pyrexia


Immune System Disorders: anaphylaxis; hypersensitivity reactions, including angioedema, drug rash with eosinophilia and systemic symptoms (DRESS), pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia


[see


Contraindications (4),


Warnings and Precautions (5.1)]


Infections and Infestations: Clostridium difficile–associated diarrhea


[see


Warnings and Precautions (5.6)]


Laboratory Investigations: platelet count decreased


Musculoskeletal Disorders: myoglobin increased; rhabdomyolysis (some reports involved patients treated concurrently with daptomycin and HMG-CoA reductase inhibitors)


[see


Warnings and Precautions (5.2),


Drug Interactions (7.1), and


Clinical Pharmacology (12.3)]


Respiratory, Thoracic, and Mediastinal Disorders: cough, eosinophilic pneumonia, organizing pneumonia


[see


Warnings and Precautions (5.3)]


Nervous System Disorders: peripheral neuropathy


[see


Warnings and Precautions (5.4)]


Skin and Subcutaneous Tissue Disorders: serious skin reactions, including Stevens-Johnson syndrome and vesiculobullous rash (with or without mucous membrane involvement), acute generalized exanthematous pustulosis


Gastrointestinal Disorders: nausea, vomiting


Renal and urinary disorders: acute kidney injury, renal insufficiency, and renal failure


Special Senses: visual disturbances

7.1 Hmg-Coa Reductase Inhibitors

In healthy adult subjects, concomitant administration of daptomycin and simvastatin had no effect on plasma trough concentrations of simvastatin, and there were no reports of skeletal myopathy


[see


Clinical Pharmacology (12.3)].


However, inhibitors of HMG-CoA reductase may cause myopathy, which is manifested as muscle pain or weakness associated with elevated levels of creatine phosphokinase (CPK). In the adult Phase 3


S. aureus bacteremia/endocarditis trial, some patients who received prior or concomitant treatment with an HMG-CoA reductase inhibitor developed elevated CPK


[see


Adverse Reactions (6.1)].


Experience with the coadministration of HMG-CoA reductase inhibitors and daptomycin in patients is limited; therefore, consideration should be given to suspending use of HMG-CoA reductase inhibitors temporarily in patients receiving daptomycin.

7.2 Drug-Laboratory Test Interactions

  • Clinically relevant plasma concentrations of daptomycin have been observed to cause a significant concentration-dependent false prolongation of prothrombin time (PT) and elevation of International Normalized Ratio (INR) when certain recombinant thromboplastin reagents are utilized for the assay. The possibility of an erroneously elevated PT/INR result due to interaction with a recombinant thromboplastin reagent may be minimized by drawing specimens for PT or INR testing near the time of trough plasma concentrations of daptomycin. However, sufficient daptomycin concentrations may be present at trough to cause interaction.If confronted with an abnormally high PT/INR result in a patient being treated with daptomycin, it is recommended that clinicians:Repeat the assessment of PT/INR, requesting that the specimen be drawn just prior to the next daptomycin dose (i.e., at trough concentration). If the PT/INR value obtained at trough remains substantially elevated above what would otherwise be expected, consider evaluating PT/INR utilizing an alternative method.Evaluate for other causes of abnormally elevated PT/INR results.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients below the age of one year have not been established. Avoid use of daptomycin in pediatric patients younger than one year of age due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) observed in neonatal dogs

[see


Warnings and Precautions (5.5) and


Nonclinical Toxicology (13.2)].


Daptomycin is not indicated in pediatric patients with renal impairment because dosage has not been established in these patients.Daptomycin has not been studied in pediatric patients with other bacterial infections.Pediatric use information is approved for Merck & Co., Inc.’s Cubicin (daptomycin for injection). However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

8.5 Geriatric Use

Of the 534 adult patients treated with daptomycin in Phase 3 controlled clinical trials of complicated skin and skin structure infections (cSSSI), 27% were 65 years of age or older and 12% were 75 years of age or older. Of the 120 adult patients treated with daptomycin in the Phase 3 controlled clinical trial of


S. aureus bacteremia/endocarditis, 25% were 65 years of age or older and 16% were 75 years of age or older. In Phase 3 adult clinical trials of cSSSI and


S. aureus bacteremia/endocarditis, clinical success rates were lower in patients ≥65 years of age than in patients <65 years of age. In addition, treatment-emergent adverse events were more common in patients ≥65 years of age than in patients <65 years of age.


The exposure of daptomycin was higher in healthy elderly subjects than in healthy young adult subjects. However, no adjustment of daptomycin dosage is warranted for elderly patients with creatinine clearance (CL


CR) ≥30 mL/min


[see


Dosage and Administration (2.6) and


Clinical Pharmacology (12.3)].

8.6 Patients With Renal Impairment

Daptomycin is eliminated primarily by the kidneys; therefore, a modification of daptomycin dosage interval is recommended for adult patients with CL


CR <30 mL/min, including patients receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD). In adult patients with renal impairment, both renal function and creatine phosphokinase (CPK) should be monitored more frequently than once weekly


[see


Dosage and Administration (2.6),


Warnings and Precautions (5.2,


5.8), and


Clinical Pharmacology (12.3)].


The dosage regimen for daptomycin in pediatric patients with renal impairment has not been established


.

10 Overdosage

In the event of overdosage, supportive care is advised with maintenance of glomerular filtration. Daptomycin is cleared slowly from the body by hemodialysis (approximately 15% of the administered dose is removed over 4 hours) and by peritoneal dialysis (approximately 11% of the administered dose is removed over 48 hours). The use of high-flux dialysis membranes during 4 hours of hemodialysis may increase the percentage of dose removed compared with that removed by low-flux membranes.

11 Description

Daptomycin for Injection contains daptomycin, a cyclic lipopeptide antibacterial agent derived from the fermentation of


Streptomyces roseosporus. The chemical name is


N-decanoyl-L-tryptophyl-D-asparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-D-seryl-


threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanine ε


1-lactone. The chemical structure is:


The empirical formula is C


72H


101N


17O


26; the molecular weight is 1620.67. Daptomycin for Injection is supplied in a single-dose vial as a sterile, nonpyrogenic, preservative-free, pale yellow to light brown, lyophilized cake/powder containing approximately 500 mg of daptomycin for intravenous (IV) use following reconstitution with 0.9% sodium chloride injection


[see


Dosage and Administration (2.7)].


The only inactive ingredient is sodium hydroxide, which is used for pH adjustment. Freshly reconstituted solutions of Daptomycin for Injection range in color from pale yellow to light brown.

12.1 Mechanism Of Action

Daptomycin is an antibacterial drug


[see


Clinical Pharmacology (12.4)].

12.2 Pharmacodynamics

Based on animal models of infection, the antimicrobial activity of daptomycin appears to correlate with the AUC/MIC (area under the concentration-time curve/minimum inhibitory concentration) ratio for certain pathogens, including


S. aureus. The principal pharmacokinetic/pharmacodynamic parameter best associated with clinical and microbiological cure has not been elucidated in clinical trials with daptomycin.

12.4 Microbiology

Daptomycin belongs to the cyclic lipopeptide class of antibacterials. Daptomycin has clinical utility in the treatment of infections caused by aerobic, Gram-positive bacteria. The


in vitro spectrum of activity of daptomycin encompasses most clinically relevant Gram-positive pathogenic bacteria.


Daptomycin exhibits rapid, concentration-dependent bactericidal activity against Gram-positive bacteria


in vitro. This has been demonstrated both by time-kill curves and by MBC/MIC (minimum bactericidal concentration/minimum inhibitory concentration) ratios using broth dilution methodology. Daptomycin maintained bactericidal activity


in vitro against stationary phase


S. aureus in simulated endocardial vegetations. The clinical significance of this is not known.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term carcinogenicity studies in animals have not been conducted to evaluate the carcinogenic potential of daptomycin. However, neither mutagenic nor clastogenic potential was found in a battery of genotoxicity tests, including the Ames assay, a mammalian cell gene mutation assay, a test for chromosomal aberrations in Chinese hamster ovary cells, an


in vivo micronucleus assay, an


in vitro DNA repair assay, and an


in vivo sister chromatid exchange assay in Chinese hamsters.


Daptomycin did not affect the fertility or reproductive performance of male and female rats when administered intravenously at doses of 25, 75, or 150 mg/kg/day, which is approximately up to 9 times the estimated human exposure level based upon AUCs (or approximately up to 4 times the recommended human dose of 6 mg/kg based on body surface area comparison).

15 References

  • Liu SL, Howard LC, Van Lier RBL, Markham JK: Teratology studies with daptomycin administered intravenously (iv) to rats and rabbits. Teratology 37(5):475, 1988.Stroup JS, Wagner J, Badzinski T: Use of daptomycin in a pregnant patient with Staphylococcus aureus endocarditis. Ann Pharmacother 44(4):746-749, 2010.Buitrago MI, Crompton JA, Bertolami S, North DS, Nathan RA. Extremely low excretion of daptomycin into breast milk of a nursing mother with methicillin-resistant
  • Staphylococcus aureus pelvic inflammatory disease. Pharmacotherapy 2009;29(3):347–351.
  • Klibanov OM, Vickery S, Nortey C: Successful treatment of infective panniculitis with daptomycin in a pregnant, morbidly obese patient. Ann Pharmacother 48(5):652-655, 2014.Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, Bashore T, Corey GR. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633–638.

16 How Supplied/Storage And Handling

Daptomycin for Injection is supplied as a sterile, nonpyrogenic, preservative-free pale yellow to light brown lyophilized cake/powder in a single-dose 20 mL vial containing 500 mg of daptomycin: Package of 1 (NDC 0143-9378-01).The container closure is not made with natural rubber latex.

17 Patient Counseling Information

Advise patients that allergic reactions, including serious allergic reactions, could occur and that serious reactions require immediate treatment. Patients should report any previous allergic reactions to daptomycin.


[See


Warnings and Precautions (5.1).]


Advise patients to report muscle pain or weakness, especially in the forearms and lower legs, as well as tingling or numbness.


[See


Warnings and Precautions (5.2,


5.4).]


Advise patients to report any symptoms of cough, breathlessness, or fever.


[See


Warnings and Precautions (5.3).]


Advise patients that diarrhea is a common problem caused by antibacterials that usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever), even as late as 2 or more months after having received the last dose of the antibacterial. If this occurs, patients should contact their physician as soon as possible.


[See


Warnings and Precautions (5.6).]


Counsel patients that antibacterial drugs, including daptomycin, should be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When daptomycin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be administered exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by daptomycin or other antibacterial drugs in the future.

* Please review the disclaimer below.