oritavancin 1200 MG Injection

INDICATIONS AND USAGE KIMYRSA is a lipoglycopeptide antibacterial drug indicated for the treatment of adult patients with acute bacterial skin and skin structure infections caused or suspected to be caused by susceptible isolates of designated Gram-positive microorganisms. ( 1.1 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of KIMYRSA and other antibacterial drugs, KIMYRSA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.2 ) 1.1 Acute Bacterial Skin and Skin Structure Infections KIMYRSA ® 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 KIMYRSA and other antibacterial drugs, KIMYRSA 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.

DOSAGE AND ADMINISTRATION There are two oritavancin products (KIMYRSA and ORBACTIV ® , another oritavancin product) that have differences in dose strength, duration of infusion and preparation instructions, including reconstitution and dilution instructions and compatible diluents ( 2.1 , 2.2 , 2.3 , 2.4 ) Administer 1,200 mg of KIMYRSA as a single dose by intravenous infusion over 1 hour. ( 2.1 , 5.3 ) Carefully follow the recommended dosage and dose preparation instructions for KIMYRSA in the full prescribing information. ( 2.1 , 2.2 , 2.3 ) 2.1 Dosage and Administration Overview There are two oritavancin products (KIMYRSA and ORBACTIV ® , 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 KIMYRSA in this prescribing information (PI) [see Dosage and Administration (2.1 , 2.2 , 2.3 , 2.4) ]. Refer to the ORBACTIV prescribing information for relevant information of the other oritavancin product. 2.2 Recommended Dosage The recommended dosage of KIMYRSA is 1,200 mg administered as a single dose by intravenous infusion over 1 hour in patients 18 years and older [see Warnings and Precautions (5.3) ] . 2.3 Preparation of KIMYRSA for Intravenous Infusion There are two oritavancin products (KIMYRSA and ORBACTIV, 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 KIMYRSA specified in this prescribing information. Refer to the ORBACTIV prescribing information for relevant information of the other oritavancin product. KIMYRSA is intended for intravenous infusion, only after reconstitution and dilution. One KIMYRSA 1,200 mg single-dose vial needs to be reconstituted and diluted to prepare a single 1,200 mg intravenous dose. Reconstitution : Aseptic technique should be used to reconstitute one KIMYRSA 1,200 mg vial. Add 40 mL of sterile water for injection (SWFI) to reconstitute the vial to provide a 30 mg/mL solution. Gently swirl the contents to avoid foaming and ensure that all KIMYRSA 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. The reconstituted vial should appear to be a clear, colorless to pink solution, free of visible particles. Dilution : Use 0.9% sodium chloride injection or 5% dextrose in sterile water (D5W) for dilution to prepare the final intravenous solution for infusion. Since no preservative or bacteriostatic agent is present in KIMYRSA, aseptic technique must be used in preparing the final intravenous solution as follows: Withdraw and discard 40 mL from a 250 mL intravenous bag of 0.9% sodium chloride injection or D5W. Withdraw 40 mL of the reconstituted vial of KIMYRSA and add to the intravenous bag of 0.9% sodium chloride injection or D5W to bring the bag volume to 250 mL. This yields a concentration of 4.8 mg/mL. Discard any unused portion of the reconstituted solution remaining in the vial. Storage and Use of Intravenous Solution : Diluted intravenous solution in an infusion bag should be used within 4 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 1 hour infusion time should not exceed 4 hours at room temperature or 12 hours if refrigerated. 2.4 Compatibilities KIMYRSA solution for administration by 1-hour infusion is compatible with: 0.9% sodium chloride injection 5% dextrose in sterile water (D5W) 2.5 Incompatibilities Drugs formulated at a basic or neutral pH may be incompatible with KIMYRSA. KIMYRSA 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 KIMYRSA with 0.9% sodium chloride injection or D5W.

WARNINGS AND PRECAUTIONS Coagulation test interference: Oritavancin has been shown to artificially prolong aPTT for up to 120 hours, and may prolong PT and INR for up to 12 hours and ACT for up to 24 hours. For patients who require aPTT monitoring within 120 hours of KIMYRSA dosing, consider a non-phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT. ( 5.1 , 7.2 ) Serious hypersensitivity reactions, including anaphylaxis, have been reported with the use of oritavancin products, including KIMYRSA. Discontinue infusion if signs of acute hypersensitivity occur. Carefully monitor patients with known hypersensitivity to glycopeptides. ( 5.2 ) Infusion Related Reactions: Infusion related reactions have been reported with the glycopeptide class of antimicrobial agents, including oritavancin products (e.g. KIMYRSA). Stopping or slowing the infusion may result in cessation of these reactions. ( 5.3 ) Clostridioides difficile -Associated Diarrhea: Evaluate patients if diarrhea occurs. ( 5.4 ) Concomitant warfarin use: Oritavancin has been shown to artificially prolong PT/INR for up to 12 hours ( 5.1 ). Patients should be monitored for bleeding if concomitantly receiving KIMYRSA and warfarin. ( 5.5 ) Osteomyelitis: Institute appropriate alternate antibacterial therapy in patients with confirmed or suspected osteomyelitis. ( 5.6 ) 5.1 Coagulation Test Interference Oritavancin 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. Oritavancin has also been shown to elevate D-dimer concentrations up to 72 hours after oritavancin administration. For patients who require aPTT monitoring within 120 hours of KIMYRSA 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) ] . Oritavancin 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 KIMYRSA. If an acute hypersensitivity reaction occurs during KIMYRSA infusion, discontinue KIMYRSA immediately and institute appropriate supportive care. Before using KIMYRSA, inquire carefully about previous hypersensitivity reactions to glycopeptides. Due to the possibility of cross-sensitivity, carefully monitor for signs of hypersensitivity during KIMYRSA infusion in patients with a history of glycopeptide allergy. In the Phase 3 ABSSSI clinical trials, the median onset of hypersensitivity reactions in oritavancin-treated patients was 1.2 days and the median duration of these reactions was 2.4 days [see Adverse Reactions (6.1) ] . 5.3 Infusion Related Reactions Infusion related reactions have been reported with the glycopeptide class of antimicrobial agents, including oritavancin products (e.g. KIMYRSA), including flushing of the upper body, urticaria, pruritus and/or rash [see Adverse Reactions (6.1) ] . Infusion reactions characterized by chest pain, back pain, chills and tremor have been observed with the use of oritavancin, including after the administration of more than one dose of oritavancin during a single course of therapy. Stopping or slowing the infusion may result in cessation of these reactions. The safety and effectiveness of more than one dose of KIMYRSA during a single course of therapy have not been established [see Dosage and Administration (2.2) ]. 5.4 Clostridioides difficile -Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including oritavancin products (e.g. KIMYRSA), and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents. If CDAD is suspected or confirmed, antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated . 5.5 Potential Risk of Bleeding with Concomitant Use of Warfarin Oritavancin has been shown to artificially prolong prothrombin time (PT) and international normalized ratio (INR) for up to 12 hours, making the monitoring of the anticoagulation effect of warfarin unreliable up to 12 hours after an oritavancin dose [see Warnings and Precautions (5.1) ] . Patients should be monitored for bleeding if concomitantly receiving KIMYRSA and warfarin [see Drug Interactions (7.1) ] . 5.6 Osteomyelitis In Phase 3 ABSSSI clinical trials, more cases of osteomyelitis were reported in the oritavancin treated arm than in the vancomycin-treated arm. Monitor patients treated with KIMYRSA for signs and symptoms of osteomyelitis. If osteomyelitis is suspected or diagnosed, institute appropriate alternate antibacterial therapy [see Adverse Reactions (6.1) ] . 5.7 Development of Drug Resistant Bacteria Prescribing KIMYRSA in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see Patient Counseling Information (17) ] .

CONTRAINDICATIONS Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after KIMYRSA administration. ( 4.1 , 5.1 ) Known hypersensitivity to oritavancin products. ( 4.2 , 5.2 ) 4.1 Intravenous Unfractionated Heparin Sodium Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after KIMYRSA administration because the activated partial thromboplastin time (aPTT) test results may remain falsely elevated for up to 120 hours (5 days) after KIMYRSA administration [see Warnings and Precautions (5.1) and Drug Interactions (7.2) ]. 4.2 Hypersensitivity KIMYRSA is contraindicated in patients with known hypersensitivity to oritavancin products.

Mechanism of Action Oritavancin is an antibacterial drug [see Microbiology (12.4) ] .