Daptomycin (Page 2 of 10)

2.7 Preparation and Administration of Daptomycin for Injection

There are two formulations of daptomycin that have differences concerning storage and reconstitution. Carefully follow the reconstitution and storage procedures in labeling.

Reconstitution of Daptomycin for Injection Vial

Daptomycin for Injection is supplied in single-dose vials, each containing 500 mg daptomycin as a sterile, lyophilized cake or powder. The contents of a Daptomycin for Injection 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 for Injection 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 for Injection 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 for Injection cake or powder is wetted by gently rotating the vial.
    a.
    Allow the wetted product to stand undisturbed for 10 minutes.
    b.
    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:

Adults

Intravenous Injection over a period of 2 minutes

  • For intravenous (IV) injection over a period of 2 minutes in adult patients only: Administer the appropriate volume of the reconstituted Daptomycin for Injection (concentration of 50 mg/mL).

Intravenous Infusion over a period of 30 minutes

  • For IV infusion over a period of 30 minutes in adult patients: The appropriate volume of the reconstituted Daptomycin for Injection (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 for Injection described below. Discard unused portions of Daptomycin for Injection.

In-Use Storage Conditions for Daptomycin for Injection 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 and up to 48 hours if stored under refrigeration at 2 to 8°C (36 to 46°F).

The diluted solution is stable in the infusion bag for 12 hours at room temperature 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.

Pediatric use information is approved for Merck & Co., Inc.’s Cubicin (daptomycin for injection). However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

2.8 Compatible Intravenous Solutions

Daptomycin for Injection is compatible with 0.9% sodium chloride injection and lactated Ringer’s injection.

2.9 Incompatibilities

Daptomycin for Injection is not compatible with dextrose-containing diluents.

Daptomycin for Injection 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 for Injection with other IV substances, additives and other medications should not be added to Daptomycin for Injection single-dose vials or infusion bags, or infused simultaneously with Daptomycin for Injection 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 for Injection.

3 DOSAGE FORMS AND STRENGTHS

For Injection: 500 mg daptomycin as a sterile, pale yellow to light brown lyophilized cake or powder for reconstitution in a single-dose vial.

4 CONTRAINDICATIONS

Daptomycin for Injection is contraindicated in patients with known hypersensitivity to daptomycin.

5 WARNINGS AND PRECAUTIONS

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.

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