Posology : מינונים

2       DOSAGE AND ADMINISTRATION

2.1      Important Administration Duration Instructions
Administer the appropriate volume of the reconstituted Daptomycin Medi-Market (concentration of 50 mg/mL) intravenously either by injection over a two (2) minute period or by intravenous infusion over a thirty (30) minute period [see Dosage and Administration (2.2, 2.3, 2.5)].

2.2      Dosage for Complicated Skin and Skin Structure Infections

Administer Daptomycin Medi-Market 4 mg/kg intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days.

2.3      Dosage in Patients with Staphylococcus aureus Bloodstream Infections
(Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates

Administer Daptomycin Medi-Market 6 mg/kg 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.

2.4      Dosage in Patients with Renal Impairment

No dosage adjustment is required in adult patients with creatinine clearance (CLCR) greater than or equal to 30 mL/min. The recommended dosage regimen for Daptomycin Medi-Market in adult patients with CLCR less than 30 mL/min, including adult patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), is 4 mg/kg (cSSSI) or 6 mg/kg (S. aureus bloodstream infections) once every 48 hours (Table 1). When possible, Daptomycin Medi- Market should be administered following the completion of hemodialysis, on hemodialysis days [see Warnings and Precautions (5.2, 5.10), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

Table 1: Recommended Dosage of Daptomycin Medi-Market in Adult Patients Dosage Regimen
Creatinine Clearance
(CLCR)                cSSSI                  S. aureus Bloodstream
Infections
Greater than or       4 mg/kg once every 24 hours    6 mg/kg once every 24 hours equal to 30 mL/min

Less than 30 mL/min,         4 mg/kg once every 48 hours*         6 mg/kg once every 48 hours* including hemodialysis and CAPD
*    When possible, administer Daptomycin Medi-Market following the completion of hemodialysis, on hemodialysis days.

2.5        Preparation and Administration of Daptomycin Medi-Market

Reconstitution of Daptomycin Medi-Market Vial
Daptomycin Medi-Market is supplied in single-dose vials, each containing 500 mg daptomycin as a sterile, lyophilized powder. The contents of a Daptomycin Medi-Market vial should be reconstituted with 0.9% sodium chloride injection, using aseptic technique, to 50 mg/mL as follows:

1. To minimize foaming, AVOID vigorous agitation or shaking of the vial during or after reconstitution.
2. Remove the polypropylene flip-off cap from the Daptomycin Medi-Market vial to expose the central portion of the rubber stopper.
3. Wipe the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow to dry. After cleaning, do not touch the rubber stopper or allow it to touch any other surface.
4. Slowly transfer 10 mL of 0.9% sodium chloride injection through the center of the rubber stopper into the Daptomycin Medi-Market vial, pointing the transfer needle toward the wall of the vial. It is recommended that a beveled sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device is used, pointing the transfer needle toward the wall of the vial.
5. Ensure that all of the Daptomycin Medi-Market powder is wetted by gently rotating the vial.
1. Allow the wetted product to stand undisturbed for 10 minutes.
2. Gently rotate or swirl the vial contents for a few minutes, as needed, to obtain a completely reconstituted solution.

Administration Instructions

Parenteral drug products should be inspected visually for particulate matter prior to administration.

Slowly remove reconstituted liquid (50 mg daptomycin/mL) from the vial using a beveled sterile needle that is 21 gauge or smaller in diameter. Administer as an intravenous injection or infusion as described below:

Intravenous Injection over a period of 2 minutes

•       For intravenous (IV) injection over a period of 2 minutes: Administer the appropriate volume of the reconstituted Daptomycin Medi-Market (concentration of 50 mg/mL).

Intravenous Infusion over a period of 30 minutes

•     For intravenous (IV) infusion over a period of 30 minutes: The appropriate volume of the reconstituted Daptomycin Medi-Market (concentration of 50 mg/mL) should be further diluted, using aseptic technique, into a 50 mL IV infusion bag containing 0.9% sodium chloride injection.

No preservative or bacteriostatic agent is present in this product. Aseptic technique must be used in the preparation of final IV solution. Do not exceed the In-Use storage conditions of the reconstituted and diluted solutions of Daptomycin Medi-Market described below. Discard unused portions of Daptomycin Medi-Market.

In-Use Storage Conditions for Daptomycin Medi-Market Once Reconstituted in Acceptable Intravenous Diluents

Chemical and physical in-use stability of the reconstituted solution in the vial has been demonstrated for 12 hours at 25°C and up to 48 hours at 2°C to 8°C.

Chemical and physical stability of the diluted solution in infusion bags is established as 12 hours at 25°C or 24 hours at 2 °C – 8 °C.
For the 30-minute intravenous infusion, the combined storage time (reconstituted solution in vial and diluted solution in infusion bag) must not exceed 12 hours at 25°C or 24 hours at 2°C - 8°C.
For the 2-minute intravenous injection, the storage time of the reconstituted solution in the vial at 25 °C must not exceed 12 hours or 48 hours at 2 °C – 8 °C.
However, from a microbiological point of view the product should be used immediately. No preservative or bacteriostatic agent is present in this product. If not used immediately, in-use storage times are the responsibility of the user and would not normally be longer than 24 hours at 2 °C – 8 °C, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.

2.6      Compatible Intravenous Solution for Reconstitution and Dilution

Daptomycin Medi-Market is compatible with 0.9% sodium chloride injection for reconstitution.
Reconstituted Daptomycin Medi-Market can only be diluted with 0.9% sodium chloride injection.

2.7      Incompatibilities

Daptomycin Medi-Market is not compatible with dextrose-containing diluents.
Daptomycin Medi-Market 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 Medi-Market with other IV substances, additives and other medications should not be added to Daptomycin Medi-Market single-dose vials or infusion bags, or infused simultaneously with Daptomycin Medi-Market 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 Medi-Market.