Bedapt Daptomycin Special Precautions

Anaphylaxis/Hypersensitivity Reactions: Anaphylaxis/hypersensitivity reactions have been reported with the use of antibacterial agents, including daptomycin for injection. If an allergic reaction to daptomycin for injection occurs, discontinue the drug and institute appropriate therapy.
Pneumonia: Daptomycin for injection should not be used for the treatment of pneumonia. It has been demonstrated in clinical studies that Daptomycin for injection is not effective in the treatment of community-acquired pneumonia, due to binding to pulmonary surfactant and consequent inactivation.
Skeletal Muscle Effects: Increases in plasma CPK levels, muscular pains, weakness, and/or rhabdomyolysis have been reported during therapy with Daptomycin for injection.
It is recommended that: Patients receiving Daptomycin for injection be monitored for the development of muscle pain or weakness, particularly of the distal extremities.
In patients who receive Daptomycin for injection, CPK levels be measured at baseline and at regular intervals (at least 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 patients with renal impairment, both renal function and CPK be monitored more frequently than once weekly.
Daptomycin for injection be discontinued in patients with unexplained signs and symptoms of myopathy in conjunction with CPK elevations to levels greater than 1000 U/L (approximately 5 times upper limit of normal [ULN]) and in patients without reported symptoms who have marked elevations in CPK, with levels greater than 2000 U/L (≥10x ULN).
Consideration be given to suspending agents associated with rhabdomyolysis, such as HMG-CoA reductase inhibitors, temporarily in patients receiving Daptomycin for injection.
Peripheral Neuropathy: Physicians should be alert to signs and symptoms of peripheral neuropathy in patients receiving Daptomycin for injection.
Pediatric patients younger than one-year-old should not be given Daptomycin for injection due to the risk of potential effects on muscular, neuromuscular, and/or nervous systems (either peripheral and/or central) that were observed in neonatal dogs.
Eosinophilic Pneumonia: Eosinophilic pneumonia has been reported in patients receiving Daptomycin for injection. 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.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): DRESS has been reported in post-marketing experience with daptomycin. Patients who develop fever, skin rash, peripheral eosinophilia, and systemic organ (for example, hepatic, pulmonary or renal) impairment while receiving Daptomycin for injection should undergo medical evaluation. If DRESS is suspected, Daptomycin for injection should be discontinued promptly and appropriate treatment instituted.
Tubulointerstitial Nephritis (TIN): TIN has been reported in post-marketing experience with daptomycin. Patients who develop new or worsening renal impairment while receiving Daptomycin for injection should undergo medical evaluation. If TIN is suspected, Daptomycin for injection should be discontinued promptly and appropriate treatment instituted.
Clostridioides difficile-Associated Diarrhea: Clostridioides difficile-associated diarrhea (CDAD) has been reported with the use of nearly all antibacterial agents, including Daptomycin for injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
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.
Drug-Laboratory Test Interactions: False prolongation of prothrombin time (PT) and elevation of International Normalized Ratio (INR) have been observed when certain recombinant thromboplastin reagents are utilized for the assay [see Interference with Laboratory Tests under Adverse Reactions].
Non-Susceptible Microorganisms: The use of antibacterials may promote the overgrowth of non-susceptible microorganisms. If superinfection occurs during therapy, take appropriate measures.
Use in Specific Populations: Renal Impairment: Daptomycin is eliminated primarily by the kidneys; therefore, an adjustment of Daptomycin for injection dosage interval is recommended for adult patients with CL_CR <30 mL/min, including patients receiving hemodialysis or CAPD. The recommended dosing regimen for these patients is 4 mg/kg (cSSSI) or 6 mg/kg (S. aureus bloodstream infections) once every 48 hours. When possible, administer Daptomycin for injection following the completion of hemodialysis on hemodialysis days. In adult patients with renal impairment, monitor both renal function and CPK more frequently than once weekly.
No dosage interval adjustment is required for patients with CL_CR ≥30 mL/min.
The dosage regimen for Daptomycin for injection in pediatric patients with renal impairment has not been established [see Renal Impairment under Dosage & Administration].
Hepatic Impairment: No dosage adjustment is warranted when Daptomycin for injection is administered to patients with mild to moderate hepatic impairment (Child-Pugh Class B). The pharmacokinetics of daptomycin in patients with severe hepatic impairment (Child-Pugh Class C) have not been evaluated.
Gender: No dosage adjustment is warranted based on gender when Daptomycin for injection is administered.
Obesity: No adjustment of Daptomycin for injection dosage is warranted in obese patients.
Use in Children: The safety and effectiveness of Daptomycin for injection in patients 1 to 17 years are supported by evidence from adequate and well-controlled studies in adults, pharmacokinetic data in pediatric patients, and additional data from two prospective studies in pediatric patients 1 to 17 years of age with cSSSI and pediatric patients 2 to 17 years of age with Staphylococcus aureus Bloodstream Infections (bacteremia).
In clinical trials, 372 pediatric patients (3 months to 17 years of age) were given intravenous Daptomycin for injection. Pharmacokinetic studies enrolled a total of 61 pediatric patients, and an additional 256 and 55 pediatric patients received Daptomycin for injection in the prospective studies of cSSSI (DAP-PEDS-07-03) and bacteremia (DAP-PEDBAC-11-02), respectively.
Use in the Elderly: No adjustment of Daptomycin for injection dosage is warranted for elderly patients with CL_CR ≥30 mL/min.