Posology : מינונים

2      DOSAGE AND ADMINISTRATION

2.1    Important Administration Duration Instructions

Administer the appropriate volume of the reconstituted DAPTOMYCIN S.K (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 S.K 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 S.K 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 S.K 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 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 S.K 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 S.K 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 S.K in Adult Patients
Dosage Regimen
Creatinine Clearance
(CLCR)                                               S. aureus Bloodstream cSSSI
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 S.K following the completion of hemodialysis on hemodialysis days.


2.5      Preparation and Administration of DAPTOMYCIN S.K

Reconstitution of DAPTOMYCIN S.K Vial

DAPTOMYCIN S.K 350 mg powder for solution for injection or infusion
To prepare DAPTOMYCIN S.K 350 mg for intravenous infusion (50 mg/Ml), please adhere to the following instructions:
Aseptic technique should be used throughout to reconstitute or dilute lyophilised DAPTOMYCIN S.K 350 mg.
For Reconstitution:
1. The polypropylene flip off cap should be removed to expose the central portions of the rubber stopper. 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. Draw 7 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into a syringe using a sterile transfer needle that is 21 gauge or smaller in diameter, or a needleless device, then slowly inject through the centre of the rubber stopper into the vial pointing the needle towards the wall of the vial.
2. The vial should be gently rotated to ensure complete wetting of the product and then allowed to stand for 10 minutes.
3. Finally the vial should be gently rotated/swirled for a few minutes as needed to obtain a clear reconstituted solution. Vigorous shaking/agitation should be avoided to prevent foaming of the product.
4. The reconstituted solution should be checked carefully to ensure that the product is in solution and visually inspected for the absence of particulates prior to use. Reconstituted solutions of DAPTOMYCIN S.K 350 mg range in colour from pale yellow to light brown.


DAPTOMYCIN S.K is supplied in single-dose vials, each containing 500 mg daptomycin as a sterile, lyophilized powder. The contents of a DAPTOMYCIN S.K vial should be reconstituted, 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 S.K 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 S.K 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 S.K 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.
Reconstituted solutions of DAPTOMYCIN S.K range in colour from pale yellow to light brown.

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 S.K (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 S.K (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 S.K described below. Discard unused portions of DAPTOMYCIN S.K.

In-Use Storage Conditions for DAPTOMYCIN S.K Once Reconstituted in Acceptable Intravenous Diluents 
Stability studies have shown that the reconstituted solution is stable in the vial for 12 hours at room temperature (25oC) and up to 48 hours if stored under refrigeration at 2°C to 8°C.

The diluted solution is stable in the infusion bag for 12 hours at room temperature (25oC) and 48 hours if stored under refrigeration. The combined storage time (reconstituted solution in vial and diluted solution in infusion bag) should not exceed 12 hours at room temperature or 48 hours under refrigeration.
2.6     Compatible Intravenous Solutions

DAPTOMYCIN S.K is compatible with 0.9% sodium chloride injection

2.7      Incompatibilities
DAPTOMYCIN S.K is not compatible with dextrose-containing diluents.

DAPTOMYCIN S.K should not be used in conjunction with ReadyMED® elastomeric infusion pumps.
Stability studies of DAPTOMYCIN S.K solutions stored in ReadyMED® elastomeric infusion pumps identified an impurity (2-mercaptobenzothiazole) leaching from this pump system into the DAPTOMYCIN S.K solution.

Because only limited data are available on the compatibility of DAPTOMYCIN S.K with other IV substances, additives and other medications should not be added to DAPTOMYCIN S.K single-dose vials or infusion bags, or infused simultaneously with DAPTOMYCIN S.K 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 S.K.