Oritavancin Diphosphate

5 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) ] .