Generic: DAPTOMYCIN
Lipopeptide Antibacterial [EPC]
1 INDICATIONS AND USAGE Daptomycin for Injection is a lipopeptide antibacterial indicated for the treatment of: • Complicated skin and skin structure infections (cSSSI) in adult patients ( 1.1 ) and, • Staphylococcus aureus bloodstream infections (bacteremia), in adult patients including those with right-sided infective endocarditis, ( 1.2 ) Limitations of Use: • This Daptomycin for Injection product is not approved for use in pediatric patients. ( 1.3 ) • Daptomycin for Injection is not indicat...
1 INDICATIONS AND USAGE Daptomycin for Injection is a lipopeptide antibacterial indicated for the treatment of: • Complicated skin and skin structure infections (cSSSI) in adult patients ( 1.1 ) and, • Staphylococcus aureus bloodstream infections (bacteremia), in adult patients including those with right-sided infective endocarditis, ( 1.2 ) Limitations of Use: • This Daptomycin for Injection product is not approved for use in pediatric patients. ( 1.3 ) • Daptomycin for Injection is not indicated for the treatment of pneumonia. ( 1.3 ) • Daptomycin for Injection is not indicated for the treatment of left-sided infective endocarditis due to S. aureus . ( 1.3 ) • 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. ( 1.3 ) 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. ( 1.4 ) 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). 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 Limitations of Use This Daptomycin for Injection product is not approved for use in pediatric patients [see Use in Specific Populations (8.4) ] . 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) ] . 1.4 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.
5 WARNINGS AND PRECAUTIONS • Anaphylaxis/hypersensitivity reactions (including life-threatening): Discontinue Daptomycin for Injection and treat sign/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 for Injection. ( 5.2 ) • Eosinophilic pneumonia: Discontinue Daptomycin for Injection and consider treatment with systemic steroids. ( 5.3 ) • Drug Reaction with Eosinophi...
5 WARNINGS AND PRECAUTIONS • Anaphylaxis/hypersensitivity reactions (including life-threatening): Discontinue Daptomycin for Injection and treat sign/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 for Injection. ( 5.2 ) • Eosinophilic pneumonia: Discontinue Daptomycin for Injection and consider treatment with systemic steroids. ( 5.3 ) • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue Daptomycin for Injection and institute appropriate treatment. ( 5.4 ) • Tubulointerstitial Nephritis (TIN): Discontinue Daptomycin for Injection 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 for Injection 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 for injection. 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 for injection was dosed more than once daily. Therefore, Daptomycin for Injection should not be dosed more frequently than once a day. Daptomycin for Injection 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 for Injection [see Drug Interactions (7.1) ]. 5.3 Eosinophilic Pneumonia Eosinophilic pneumonia has been reported in patients receiving daptomycin for injection [see Adverse Reactions (6.2) ] . In reported cases associated with daptomycin for injection, 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 for injection, and improved when daptomycin for injection 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 for Injection should undergo prompt medical evaluation, and Daptomycin for Injection 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 for injection [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 for Injection should undergo medical evaluation. If DRESS is suspected, discontinue Daptomycin for Injection promptly and institute appropriate treatment. 5.5 Tubulointerstitial Nephritis (TIN) TIN has been reported in post-marketing experience with daptomycin for injection [see Adverse Reactions (6.2) ] . Patients who develop new or worsening renal impairment while receiving Daptomycin for Injection should undergo medical evaluation. If TIN is suspected, discontinue Daptomycin for Injection promptly and institute appropriate treatment. 5.6 Peripheral Neuropathy Cases of peripheral neuropathy have been reported during the daptomycin for injection post-marketing experience [see Adverse Reactions (6.2) ]. Therefore, physicians should be alert to signs and symptoms of peripheral neuropathy in patients receiving Daptomycin for Injection. 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 for Injection 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 for injection, 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) ]. 5.10 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 for injection treatment in adult patients with creatinine clearance (CL CR ) <50 mL/min; only 31/534 (6%) patients treated with daptomycin for injection in the intent-to-treat (ITT) population had a baseline CL CR <50 mL/min. Table 2 shows the number of adult patients by renal function and treatment group who were clinical successes in the Phase 3 cSSSI trials. Table 2: 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 for Injection 4 mg/kg every 24h Comparator 50–70 mL/min 25/38 (66%) 30/48 (63%) 30–<50 mL/min 7/15 (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 for injection-treated adult patients were lower in patients with baseline CL CR <50 mL/min (see Table 3 ). A decrease of the magnitude shown in Table 3 was not observed in comparator-treated patients. Table 3: 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 for Injection 6 mg/kg every 24h Comparator Bacteremia Right-Sided Infective Endocarditis Bacteremia Right-Sided Infective Endocarditis >80 mL/min 30/50 (60%) 7/14 (50%) 19/42 (45%) 5/11 (46%) 50–80 mL/min 12/26 (46%) 1/4 (25%) 13/31 (42%) 1/2 (50%) 30–<50 mL/min 2/14 (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. 5.11 Increased International Normalized Ratio (INR)/Prolonged Prothrombin Time 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) ] . 5.12 Development of Drug-Resistant Bacteria Prescribing Daptomycin for Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication 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) ] • Drug Reaction with Eosinophilia and Systemic Symptoms [see Warnings and Precautions (5.4) ] • Tubulointerstitial Nephritis [see Warnings and Precautions (5.5) ] • Periphe...
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) ] • 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 for injection 4 mg/kg were diarrhea, headache, dizziness, rash, abnormal liver function tests, elevated creatine phosphokinase (CPK), urinary tract infections hypotension, and dyspnea. ( 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 for injection 6 mg/kg were sepsis, bacteremia, abdominal pain, chest pain, edema, pharyngolaryngeal pain, pruritus, increased sweating, insomnia, elevated CPK, and hypertension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hospira at 1-800-438-1985 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 for injection 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 4. Table 4: Incidence of Adverse Reactions that Occurred in ≥2% of Adult Patients in the Daptomycin for Injection Treatment Group and ≥ the Comparator Treatment Group in Phase 3 cSSSI Trials Adverse Reaction Adult Patients n (%) Daptomycin for Injection 4 mg/kg (N=534) Comparator Comparator: vancomycin (1 g IV every 12h) or an anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, or flucloxacillin; 4 to 12 g/day IV in divided doses). (N=558) 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 for injection 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 for injection-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 5. Table 5: Incidence of Adverse Reactions that Occurred in ≥5% of Adult Patients in the Daptomycin for Injection Treatment Group and ≥ the Comparator Treatment Group in the S. aureus Bacteremia/Endocarditis Trial Adverse Reaction NOS, not otherwise specified Adult Patients n (%) Daptomycin for Injection 6 mg/kg (N=120) Comparator Comparator: vancomycin (1 g IV every 12h) or an anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, or flucloxacillin; 2 g IV every 4h), each with initial low-dose gentamicin. (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 for injection-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 for injection-treated patients than in comparator-treated patients. These differences were due to lack of therapeutic effectiveness of daptomycin for injection in the treatment of CAP in patients experiencing these adverse events [see Indications and Usage (1.3) ] . Laboratory Changes in Adults Complicated Skin and Skin Structure Infection Trials in Adults In Phase 3 cSSSI trials of adult patients receiving daptomycin for injection at a dose of 4 mg/kg, elevations in CPK were reported as clinical adverse events in 15/534 (2.8%) daptomycin for injection-treated patients, compared with 10/558 (1.8%) comparator-treated patients. Of the 534 patients treated with daptomycin, 1 (0.2%) had symptoms of muscle pain or weakness associated with CPK elevations to greater than 4 times the upper limit of normal (ULN). The symptoms resolved within 3 days and CPK returned to normal within 7 to 10 days after treatment was discontinued [see Warnings and Precautions (5.2) ] . Table 6 summarizes the CPK shifts from Baseline through End of Therapy in the cSSSI adult trials. Table 6: Incidence of CPK Elevations from Baseline during Therapy in Either the Daptomycin for Injection Treatment Group or the Comparator Treatment Group in Phase 3 cSSSI Adult Trials Change in CPK All Adult Patients Adult Patients with Normal CPK at Baseline Daptomycin for Injection 4 mg/kg Comparator Comparator: vancomycin (1 g IV every 12h) or an anti-staphylococcal semi-synthetic penicillin (i.e., nafcillin, oxacillin, cloxacillin, or flucloxacillin; 4 to 12 g/day IV in divided doses). (N=459) Daptomycin for Injection 4 mg/kg Comparator (N=392) (N=430) % n (N=374) % n % n % n Note: Elevations in CPK observed in adult patients treated with daptomycin for injection or comparator were not clinically or statistically significantly different. No Increase 90.7 390 91.1 418 91.2 341 91.1 357 Maximum Value >1× ULN ULN (Upper Limit of Normal) is defined as 200 U/L. 9.3 40 8.9 41 8.8 33 8.9 35 >2× ULN 4.9 21 4.8 22 3.7 14 3.1 12 >4× ULN 1.4 6 1.5 7 1.1 4 1.0 4 >5× ULN 1.4 6 0.4 2 1.1 4 0.0 0 >10× ULN 0.5 2 0.2 1 0.2 1 0.0 0 S. aureus Bacteremia/Endocarditis Trial in Adults In the S. aureus bacteremia/endocarditis trial in adult patients, at a dose of 6 mg/kg, 11/120 (9.2%) daptomycin for injection-treated patients, including two patients with baseline CPK levels >500 U/L, had CPK elevations to levels >500 U/L, compared with 1/116 (0.9%) comparator-treated patients. Of the 11 daptomycin for injection-treated patients, 4 had prior or concomitant treatment with an HMG-CoA reductase inhibitor. Three of these 11 daptomycin for injection-treated patients discontinued therapy due to CPK elevation, while the one comparator-treated patient did not discontinue therapy [see Warnings and Precautions (5.2) ]. 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, pruritus, hives, shortness of breath, difficulty swallowing, truncal erythema, and pulmonary eosinophilia [see Contraindications (4) and Warnings and Precautions (5.1) ] Infections and Infestations: Clostridioides difficile –associated diarrhea [see Warnings and Precautions (5.8) ] 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 (5.6) ] Skin and Subcutaneous Tissue Disorders: serious skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), vesiculobullous rash (with or without mucous membrane involvement, including Stevens-Johnson syndrome [SJS] and toxic epidermal necrolysis [TEN]), and acute generalized exanthematous pustulosis [see Warnings and Precautions (5.4) ] Gastrointestinal Disorders: nausea, vomiting Metabolic and Nutritional Disorders: hyperkalemia Renal and urinary disorders: acute kidney injury, renal insufficiency, renal failure, and tubulointerstitial nephritis (TIN) [see Warnings and Precautions (5.5) ] Special Senses: visual disturbances
Medical Disclaimer: This information is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider before making any decisions about your medications. Data sourced from openFDA.