Daptomycin (Page 3 of 10)

5.4 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.

5.5 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) ].

5.6 Clostridium difficile –Associated Diarrhea

Clostridium 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.

5.7 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 Trials (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 for Injection treatment in adult patients with creatinine clearance (CLCR ) <50 mL/min; only 31/534 (6%) patients treated with Daptomycin for Injection in the intent-to-treat (ITT) population had a baseline CLCR <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)

CLCR

Success Rate n/N (%)

Daptomycin for Injection 4 mg/kg q24h

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 Trials (14.2)], in the Daptomycin for Injection-treated adult patients were lower in patients with baseline CLCR <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 CLCR

Success Rate n/N (%)

Daptomycin for Injection 6 mg/kg q24h

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.

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