Oritavancin (Orbactiv™)

Oritavancin (ORBACTIV™)

Usual Diluents

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

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 to avoid foaming and ensure that all ORBACTIV powder is completely reconstituted in solution.  Each vial should be inspected visually for particulate matter after reconstitution and should appear to be clear, colorless to pale yellow solution.

Dilution: Use ONLY 5% dextrose in sterile water (D5W) for dilution. Do NOT use Normal Saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Use aseptic technique to:

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

WARNINGS 

DESCRIPTION 

The chemical name for oritavancin is [4"R]-22-O-(3-amino-2,3,6-trideoxy-3-C-methyl-a-L-arabino-hexopyranosyl)-N3''-[(4'-chloro[1,1'-biphenyl]-4-yl)methyl] vancomycin phosphate [1:2] [salt]. The empirical formula of oritavancin diphosphate is C86H97N10O26Cl3•2H3PO4 and the molecular weight is 1989.09.
ORBACTIV is supplied as a sterile white to off-white lyophilized powder for intravenous infusion that contains oritavancin diphosphate, mannitol (an inactive ingredient) and phosphoric acid (to adjust pH 3.1 to 4.3). Each 50 ml capacity glass vial contains 449 mg oritavancin diphosphate (equivalent to 405 mg of oritavancin, 5 mg excess is to ensure withdrawal of 400 mg oritavancin), 400 mg oritavancin (free base equivalent).

Each vial is reconstituted with sterile water for injection and further diluted with 5% Dextrose in sterile Water for intravenous infusion. Both the reconstituted solution and the diluted solution for infusion should be clear, colorless to pale yellow solution.

CLINICAL PHARMACOLOGY:

INDICATIONS AND USAGE 

Acute Bacterial Skin and Skin Structure Infections
ORBACTIV™ (Oritavancin) for injection 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).

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 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.

CONTRAINDICATIONS

Hypersensitivity
ORBACTIV is contraindicated in patients with known hypersensitivity to ORBACTIV.

PRECAUTIONS

1. Concomitant warfarin use: Co-administration of ORBACTIV and warfarin may result in higher exposure of warfarin, which may increase the risk of bleeding. Use ORBACTIV in patients on chronic warfarin therapy only when the benefits can be expected to outweigh the risk of bleeding.
2. Coagulation test interference: ORBACTIV has been shown to artificially prolong aPTT for up to 48 hours, and may prolong PT and INR for up to 24 hours.
3. Hypersensitivity reactions have been reported with the use of antibacterial agents including ORBACTIV. Discontinue infusion if signs of acute hypersensitivity occur. Monitor closely patients with known hypersensitivity to glycopeptides.
4. Infusion-related reactions have been reported. Slow the rate or interrupt infusion if infusion reaction develops.
5. Clostridium difficile-associated colitis: Evaluate patients if diarrhea occurs.
6. Osteomyelitis: Institute appropriate alternate antibacterial therapy in patients with confirmed or suspected osteomyelitis.

ADVERSE REACTIONS

The most common adverse reactions (>/= 3%) in patients treated with ORBACTIV were headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea.

To report SUSPECTED ADVERSE REACTIONS, contact The Medicines Company at 1-888-977-6326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

DOSAGE AND ADMINISTRATION 

Recommended Dosage
The recommended dosing for ORBACTIV is a single 1200 mg dose administered by intravenous infusion over 3 hours in patients 18 years and older.

Preparation of ORBACTIV for Intravenous Infusion
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 1200 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 to avoid foaming and ensure that all ORBACTIV powder is completely reconstituted in solution.  Each vial should be inspected visually for particulate matter after reconstitution and should appear to be clear, colorless to pale yellow solution.

Dilution: Use ONLY 5% dextrose in sterile water (D5W) for dilution. Do NOT use Normal Saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Use aseptic technique to:

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

Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparing the final 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.

Incompatibilities
ORBACTIV is administered intravenously. ORBACTIV should only be diluted in D5W. Do NOT use normal saline 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 normal saline should not be added to ORBACTIV single-use 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.

HOW SUPPLIED 

Storage and Stability

HOW SUPPLIED/STORAGE AND HANDLING
How Supplied/Storage
ORBACTIV is supplied as single use 50 mL capacity glass vials containing sterile lyophilized powder equivalent to 400 mg of oritavancin (NDC 65293-015-01). Three vials are packaged in a carton to supply for a single 1200 mg dose treatment (NDC 65293-015-03).

ORBACTIV vials should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).