Daptomycin

Daptomycin for Injection is a lipopeptide antibacterial indicated for the treatment of: Complicated skin and skin structure infections (cSSSI) in adult and pediatric patients (1 to 17 years of age) ( 1.1 ) and, Staphylococcus aureus bloodstream infections (bacteremia), in adult patients including those with right-sided infective endocarditis, ( 1.2 ) Staphylococcus aureus bloodstream infections (bacteremia) in pediatric patients (1 to 17 years of age). ( 1.3 ) Limitations of Use: Daptomycin for Injection is not indicated for the treatment of pneumonia. ( 1.4 ) Daptomycin for Injection is not indicated for the treatment of left-sided infective endocarditis due to S. aureus . ( 1.4 ) Daptomycin for Injection is not recommended 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. ( 1.4 ) 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 to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.5 )

1.1 Complicated Skin and Skin Structure Infections (cSSSI) Daptomycin for Injection is indicated for the treatment of adult and pediatric patients (1 to 17 years of age) 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).

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.

1.3 Staphylococcus aureus Bloodstream Infections (Bacteremia) in Pediatric Patients (1 to 17 Years of Age) Daptomycin for Injection is indicated for the treatment of pediatric patients (1 to 17 years of age) with Staphylococcus aureus bloodstream infections (bacteremia).

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 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 ( 5.7 ) 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 or prevent 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.

For Injection: 350 mg daptomycin as a sterile, pale yellow to light brown lyophilized powder for reconstitution in a single-dose vial. For Injection: 350 mg lyophilized powder for reconstitution in a single-dose vial ( 3 )

Daptomycin for injection is contraindicated in patients with known hypersensitivity to daptomycin [see Warnings and Precautions ( 5.1 )]. Known hypersensitivity to daptomycin ( 4 )

Anaphylaxis/hypersensitivity reactions (including life-threatening): Discontinue daptomycin and treat signs/symptoms. ( 5.1 ) Myopathy and rhabdomyolysis: Monitor CPK levels and follow muscle pain or weakness; if elevated CPK or myopathy occurs, consider discontinuation of daptomycin. ( 5.2 ) Eosinophilic pneumonia: Discontinue daptomycin and consider treatment with systemic steroids. ( 5.3 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue daptomycin and institute appropriate treatment. ( 5.4 ) Tubulointerstitial Nephritis (TIN): Discontinue daptomycin and institute appropriate treatment. ( 5.5 ) Peripheral neuropathy: Monitor for neuropathy and consider discontinuation. ( 5.6 ) Potential nervous system and/or muscular system effects in pediatric patients younger than 12 months: Avoid use of daptomycin in this age group. ( 5.7 ) Clostridioides difficile –associated diarrhea: Evaluate patients if diarrhea occurs. ( 5.8 ) Persisting or relapsing S. aureus bacteremia/endocarditis: Perform susceptibility testing and rule out sequestered foci of infection. ( 5.9 ) Decreased efficacy was observed in adult patients with moderate baseline renal impairment. ( 5.10 )

5.1 Anaphylaxis/Hypersensitivity Reactions Anaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including daptomycin for injection, and may be life-threatening. If an allergic reaction to Daptomycin for Injection 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 for Injection should be monitored for the development of muscle pain or weakness, particularly of the distal extremities. In patients who receive Daptomycin for Injection, 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 for Injection. 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 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) DRESS has been reported in post-marketing experience with daptomycin [see Adverse Reactions ( 6.2 )] . Patients who develop skin rash, fever, peripheral eosinophilia, and systemic organ (for example, hepatic, renal, pulmonary) impairment while receiving daptomycin should undergo medical evaluation. If DRESS is suspected, discontinue daptomycin promptly and institute appropriate treatment.

5.5 Tubulointerstitial Nephritis (TIN) TIN has been reported in post-marketing experience with daptomycin [see Adverse Reactions ( 6.2 )] . Patients who develop new or worsening renal impairment while receiving daptomycin should undergo medical evaluation. If TIN is suspected, discontinue daptomycin promptly and institute appropriate treatment.

5.6 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.

5.7 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 )] .

5.8 Clostridioides difficile –Associated Diarrhea Clostridioides 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.

5.9 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 )] . […]

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 )] Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions ( 5.4 )] Tubulointerstitial Nephritis [see Warnings and Precautions ( 5.5 )] Peripheral Neuropathy [see Warnings and Precautions ( 5.6 )] Increased International Normalized Ratio (INR)/Prolonged Prothrombin Time [see Warnings and Precautions ( 5.11 ) and Drug Interactions ( 7.2 )] Adult cSSSI Patients: The most common adverse reactions that occurred in ≥2% of adult cSSSI patients receiving daptomycin 4 mg/kg were diarrhea, headache, dizziness, rash, abnormal liver function tests, elevated creatine phosphokinase (CPK), urinary tract infections, hypotension, and dyspnea. ( 6.1 ) Pediatric cSSSI Patients: The most common adverse reactions that occurred in ≥2% of pediatric patients receiving daptomycin were diarrhea, vomiting, abdominal pain, pruritus, pyrexia, elevated CPK, and headache. ( 6.1 ) Adult S. aureus bacteremia/endocarditis Patients: The most common adverse reactions that occurred in ≥5% of S. aureus bacteremia/endocarditis patients receiving daptomycin 6 mg/kg were sepsis, bacteremia, abdominal pain, chest pain, edema, pharyngolaryngeal pain, pruritus, increased sweating, insomnia, elevated CPK, and hypertension. ( 6.1 ) Pediatric S. aureus bacteremia Patients: The most common adverse reactions that occurred in ≥5% of pediatric patients receiving daptomycin were vomiting and elevated CPK. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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. Clinical Trial Experience in Adult Patients Clinical trials enrolled 1,864 adult patients treated with daptomycin and 1,416 treated with comparator. Complicated Skin and Skin Structure Infection Trials in Adults In Phase 3 complicated skin and skin structure infection (cSSSI) trials in adult patients, daptomycin was discontinued in 15/534 (2.8%) patients due to an adverse reaction, while comparator was discontinued in 17/558 (3.0%) patients. The rates of the most common adverse reactions, organized by body system, observed in adult patients with cSSSI (receiving 4 mg/kg daptomycin) are displayed in Table 6 . Table 6: Incidence of Adverse Reactions that Occurred in ≥2% of Adult Patients in the Daptomycin Treatment Group and ≥ the Comparator Treatment Group in Phase 3 cSSSI Trials Adverse Reaction Adult Patients (%) Daptomycin 4 mg/kg (N=534) Comparator* (N=558) *Comparator: vancomycin (1 g IV q12h) or an anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, or flucloxacillin; 4 to 12 g/day IV in divided doses). Gastrointestinal disorders Diarrhea 5.2

4.3 Nervous system disorders Headache 5.4

5.4 Dizziness 2.2

2.0 Skin/subcutaneous disorders Rash 4.3

3.8 Diagnostic investigations Abnormal liver function tests 3.0

1.6 Elevated CPK 2.8

1.8 Infections Urinary tract infections 2.4

0.5 Vascular disorders Hypotension 2.4

1.4 Respiratory disorders Dyspnea 2.1

1.6 Drug-related adverse reactions (possibly or probably drug-related) that occurred in <1% of adult patients receiving daptomycin in the cSSSI trials are as follows: Body as a Whole: fatigue, weakness, rigors, flushing, hypersensitivity Blood/Lymphatic System: leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, increased International Normalized Ratio (INR) Cardiovascular System: supraventricular arrhythmia Dermatologic System: eczema Digestive System: abdominal distension, stomatitis, jaundice, increased serum lactate dehydrogenase Metabolic/Nutritional System: hypomagnesemia, increased serum bicarbonate, electrolyte disturbance Musculoskeletal System: myalgia, muscle cramps, muscle weakness, arthralgia Nervous System: vertigo, mental status change, paresthesia Special Senses: taste disturbance, eye irritation S. aureus Bacteremia/Endocarditis Trial in Adults In the S. aureus bacteremia/endocarditis trial involving adult patients, daptomycin was discontinued in 20/120 (16.7%) patients due to an adverse reaction, while comparator was discontinued in 21/116 (18.1%) patients. Serious Gram-negative infections (including bloodstream infections) were reported in 10/120 (8.3%) daptomycin-treated patients and 0/115 comparator-treated patients. Comparator-treated patients received dual therapy that included initial gentamicin for 4 days. Infections were reported during treatment and during early and late follow-up. Gram-negative infections included cholangitis, alcoholic pancreatitis, sternal osteomyelitis/mediastinitis, bowel infarction, recurrent Crohn's disease, recurrent line sepsis, and recurrent urosepsis caused by a number of different Gram-negative bacteria. The rates of the most common adverse reactions, organized by System Organ Class (SOC), observed in adult patients with S. aureus bacteremia/endocarditis (receiving 6 mg/kg daptomycin) are displayed in Table 7 . Table 7: Incidence of Adverse Reactions that Occurred in ≥5% of Adult Patients in the Daptomycin Treatment Group and ≥ the Comparator Treatment Group in the S. aureus Bacteremia/Endocarditis Trial *NOS, not otherwise specified. † Comparator: vancomycin (1 g IV q12h) or an anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, or flucloxacillin; 2 g IV q4h), each with initial low-dose gentamicin. Adverse Reaction* Adult Patients n (%) Daptomycin 6 mg/kg (N=120) Comparator † (N=116) Infections and infestations Sepsis NOS 6 (5%) 3 (3%) Bacteremia 6 (5%) 0 (0%) Gastrointestinal disorders Abdominal pain NOS 7 (6%) 4 (3%) General disorders and administration site conditions Chest pain 8 (7%) 7 (6%) Edema NOS 8 (7%) 5 (4%) Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain 10 (8%) 2 (2%) Skin and subcutaneous tissue disorders Pruritus 7 (6%) 6 (5%) Sweating increased 6 (5%) 0 (0%) Psychiatric disorders Insomnia 11 (9%) 8 (7%) Investigations Blood creatine phosphokinase increased 8 (7%) 1 (1%) Vascular disorders Hypertension NOS 7 (6%) 3 (3%) The following reactions, not included above, were reported as possibly or probably drug-related in the daptomycin-treated group: Blood and Lymphatic System Disorders: eosinophilia, lymphadenopathy, thrombocythemia, thrombocytopenia Cardiac Disorders: atrial fibrillation, atrial flutter, cardiac arrest Ear and Labyrinth Disorders: tinnitus Eye Disorders: vision blurred Gastrointestinal Disorders: dry mouth, epigastric discomfort, gingival pain, hypoesthesia oral Infections and Infestations: candidal infection NOS, vaginal candidiasis, fungemia, oral candidiasis, urinary tract infection fungal Investigations: blood phosphorous increased, blood alkaline phosphatase increased, INR increased, liver function test abnormal, alanine aminotransferase increased, aspartate aminotransferase increased, prothrombin time prolonged Metabolism and Nutrition Disorders: appetite decreased NOS Musculoskeletal and Connective Tissue Disorders: myalgia Nervous System Disorders: dyskinesia, paresthesia Psychiatric Disorders: hallucination NOS Renal and Urinary Disorders: proteinuria, renal impairment NOS Skin and Subcutaneous Tissue Disorders: pruritus generalized, rash vesicular Other Trials in Adults In Phase 3 trials of community-acquired pneumonia (CAP) in adult patients, the death rate and rates of serious cardiorespiratory adverse events were higher in daptomycin-treated patients than in comparator-treated patients. […]

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.

8.1 Pregnancy Risk Summary Limited published data on use of daptomycin in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies performed in rats and rabbits daptomycin was administered intravenously during organogenesis at doses 2 and 4-times, respectively, the recommended 6 mg/kg human dose (on a body surface area basis). No evidence of adverse developmental outcomes was observed. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In pregnant rats, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 18. Maternal body weight gain was decreased at 75 mg/kg/day. No embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than in humans at the recommended maximum dose of 6 mg/kg (based on body surface area). In pregnant rabbits, daptomycin was administered intravenously at doses of 5, 20, or 75 mg/kg/day during the gestation days 6 to 15. Maternal body weight gain and food consumption were decreased at 75 mg/kg/day. No embryo/fetal effects were noted at the highest dose of 75 mg/kg/day, a dose approximately 4-fold higher than in humans at the maximum recommended dose of 6 mg/kg (based on body surface area). In a combined fertility and pre/postnatal development study, daptomycin was administered intravenously to female rats at doses of 2, 25, 75 mg/kg/day from 14-days pre-mating through lactation/postpartum day 20). No effects on pre/postnatal development were observed up to the highest dose of 75 mg/kg/day, a dose approximately 2-fold higher than the maximum recommended human dose of 6 mg/kg (based on body surface area) 1 .

8.2 Lactation Risk Summary Limited published data report that daptomycin is present in human milk at infant doses of 0.1% of the maternal dose (see Data ) 2,3,4 . There is no information on the effects of daptomycin on the breastfed infant or the effects of daptomycin on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for daptomycin and any potential adverse effects on the breastfed infant from daptomycin or from the underlying maternal condition.

8.4 Pediatric Use The safety and effectiveness of daptomycin in the treatment of cSSSI and S. aureus bloodstream infections (bacteremia) have been established in the age groups 1 to 17 years of age. Use of daptomycin in these age groups is supported by evidence from adequate and well-controlled studies in adults, with additional data from pharmacokinetic studies in pediatric patients, and from safety, efficacy and PK studies in pediatric patients with cSSSI and S. aureus bloodstream infections [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.1 , 14.2 )] . 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 ( 5.7 ) 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.

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 , 5.10 ), and Clinical Pharmacology ( 12.3 )] . The dosage regimen for daptomycin in pediatric patients with renal impairment has not been established.

Daptomycin is an antibacterial drug [see Clinical Pharmacology ( 12.4 )] .