Orbactiv

ORBACTIV- oritavancin injection, powder, lyophilized, for solution
Melinta Therapeutics, LLC

1 INDICATIONS AND USAGE

1.1 Acute Bacterial Skin and Skin Structure Infections

ORBACTIV^® (oritavancin) is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms:

Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes , Streptococcus agalactiae , Streptococcus dysgalactiae , Streptococcus anginosus group (includes S. anginosus , S. intermedius , and S. constellatus), and Enterococcus faecalis (vancomycin-susceptible isolates only).

1.2 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ORBACTIV and other antibacterial drugs, ORBACTIV should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage and Administration Overview

There are two oritavancin products (ORBACTIV and KIMYRSA™, another oritavancin product) that:

• Are supplied in different dose strengths of oritavancin [see Dosage Forms and Strengths (3)].
• Have different recommended durations of infusion [see Dosage and Administration (2.2)].
• Have different preparation instructions, including differences in reconstitution, dilution, and compatible diluents [see Dosage and Administration (2.3, 2.4)].

Carefully follow the recommended dosage and dose preparation instructions for ORBACTIV in this prescribing information (PI) [see Dosage and Administration (2.1, 2.2, 2.3, 2.4)]. Refer to the KIMYRSA prescribing information for relevant information of the other oritavancin product.

2.2 Recommended Dosage

The recommended dosage of ORBACTIV is 1,200 mg administered as a single dose by intravenous infusion over 3 hours in patients 18 years and older [see Warnings and Precautions (5.3)].

2.3 Preparation of ORBACTIV for Intravenous Infusion

There are two oritavancin products (ORBACTIV and KIMYRSA, another oritavancin product) that have differences in dose strengths, duration of infusion, reconstitution and dilution instructions, and compatible diluents. Carefully follow the reconstitution, and dilution instructions with the appropriate compatible diluent for ORBACTIV specified in this prescribing information. Refer to the KIMYRSA prescribing information for relevant information of the other oritavancin product.

ORBACTIV is intended for intravenous infusion, only after reconstitution and dilution.

Three ORBACTIV 400 mg vials need to be reconstituted and diluted to prepare a single 1,200 mg intravenous dose.

Reconstitution: Aseptic technique should be used to reconstitute three ORBACTIV 400 mg vials.

• Add 40 mL of sterile water for injection (WFI) to reconstitute each vial to provide a 10 mg/mL solution per vial.
• For each vial, gently swirl the contents to avoid foaming and ensure that all ORBACTIV powder is completely dissolved to form a reconstituted solution.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Each reconstituted vial should appear to be a clear, colorless to pale yellow solution, free of visible particles.

Dilution: Use ONLY 5% dextrose injection (D5W) for dilution to prepare the final intravenous solution for infusion. Do NOT use Sodium Chloride Injection for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Since no preservative or bacteriostatic agent is present in ORBACTIV, aseptic technique must be used in preparing the final intravenous solution as follows:

• Withdraw and discard 120 mL from a 1000 mL intravenous bag of D5W.
• Withdraw 40 mL from each of the three reconstituted vials of ORBACTIV and add to D5W intravenous bag to bring the bag volume to 1000 mL. This yields a concentration of 1.2 mg/mL.

Discard any unused portion of the reconstituted solution remaining in each vial.

Storage and Use of Intravenous Solution: Diluted intravenous solution in an infusion bag should be used within 6 hours when stored at room temperature, or used within 12 hours when refrigerated at 2 to 8°C (36 to 46°F). The combined storage time (reconstituted solution in the vial and diluted solution in the bag) and 3 hour infusion time should not exceed 6 hours at room temperature or 12 hours if refrigerated.

2.4 Compatibility

ORBACTIV solution for administration by 3-hour infusion is ONLY compatible with:

• 5% dextrose injection (D5W)

2.5 Incompatibilities

ORBACTIV is administered intravenously. ORBACTIV should only be diluted in D5W. Do NOT use sodium chloride injection for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Therefore other intravenous substances, additives or other medications mixed in sodium chloride injection should not be added to ORBACTIV single-dose vials or infused simultaneously through the same IV line or through a common intravenous port.

In addition, drugs formulated at a basic or neutral pH may be incompatible with ORBACTIV. ORBACTIV should not be administered simultaneously with commonly used intravenous drugs through a common intravenous port. If the same intravenous line is used for sequential infusion of additional medications, the line should be flushed before and after infusion of ORBACTIV with D5W.

3 DOSAGE FORMS AND STRENGTHS

ORBACTIV is supplied as sterile, white to off-white lyophilized powder containing 400 mg of oritavancin (as oritavancin diphosphate) in a single-dose clear glass vial, which must be reconstituted and further diluted prior to intravenous administration.

4 CONTRAINDICATIONS

4.1 Intravenous Unfractionated Heparin Sodium

Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after ORBACTIV administration because the activated partial thromboplastin time (aPTT) test results may remain falsely elevated for up to 120 hours (5 days) after ORBACTIV administration [see Warnings and Precautions (5.1) and Drug Interactions (7.2)].

4.2 Hypersensitivity

ORBACTIV is contraindicated in patients with known hypersensitivity to oritavancin products.

5 WARNINGS AND PRECAUTIONS

5.1 Coagulation Test Interference

ORBACTIV has been shown to artificially prolong aPTT for up to 120 hours, PT and INR for up to 12 hours, and activated clotting time (ACT) for up to 24 hours following administration of a single 1,200 mg dose by binding to and preventing action of the phospholipid reagents commonly used in laboratory coagulation tests. ORBACTIV has also been shown to elevate D-dimer concentrations up to 72 hours after ORBACTIV administration.

For patients who require aPTT monitoring within 120 hours of ORBACTIV dosing, a non-phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT monitoring may be considered [see Contraindications (4.1) and Drug Interactions (7.2)].

ORBACTIV has no effect on the coagulation system in vivo.

5.2 Hypersensitivity

Serious hypersensitivity reactions, including anaphylaxis, have been reported with the use of oritavancin products, including ORBACTIV. If an acute hypersensitivity reaction occurs during ORBACTIV infusion, discontinue ORBACTIV immediately and institute appropriate supportive care. Before using ORBACTIV, inquire carefully about previous hypersensitivity reactions to glycopeptides. Due to the possibility of cross-sensitivity, carefully monitor for signs of hypersensitivity during ORBACTIV infusion in patients with a history of glycopeptide allergy. In the Phase 3 ABSSSI clinical trials, the median onset of hypersensitivity reactions in ORBACTIV-treated patients was 1.2 days and the median duration of these reactions was 2.4 days [see Adverse Reactions (6.1)].