Oritavancin Diphosphate: uses, dosing, side effects & brands

The following adverse reactions are also discussed in the Warnings and Precautions section of labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Infusion Related Reactions [see Warnings and Precautions (5.3) ] Clostridioides difficile -Associated Diarrhea [see Warnings and Precautions (5.4) ] Osteomyelitis [see Warnings and Precautions (5.6) ] The most common adverse reactions (≥3%) in patients treated with oritavancin products were headache, nausea, vomiting, limb and subcutaneous abscesses, and diarrhea. The adverse reactions occurring in ≥2 patients receiving KIMYRSA were hypersensitivity, pruritus, chills and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Melinta Therapeutics at 1-844-633-6568 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of oritavancin products cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of KIMYRSA has been established from adequate and well-controlled trials of another oritavancin product, ORBACTIV (hereinafter referred to as oritavancin), in patients with ABSSSI, and a study of KIMYRSA in patients with ABSSSI. Oritavancin has been evaluated in two, double-blind,…

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.

7.1 Effect of KIMYRSA on CYP Substrates A screening drug-drug interaction study indicated that oritavancin is a nonspecific, weak inhibitor (CYP2C9 and CYP2C19) or inducer (CYP3A4 and CYP2D6) of several CYP isoforms [see Clinical Pharmacology (12.3) ] . A drug-drug interaction study that assessed the interaction potential of a single 1,200 mg dose of oritavancin on the pharmacokinetics of S-warfarin (CYP2C9 probe substrate) showed no effect of oritavancin on S-warfarin C max or AUC. Avoid administering KIMYRSA concomitantly with drugs that are predominantly metabolized by one of the affected CYP450 enzymes, as co-administration may increase or decrease concentrations of those drugs. Patients should be closely monitored for signs of toxicity or lack of efficacy if they have been given KIMYRSA while on a potentially affected compound (e.g., patients should be monitored for bleeding if concomitantly receiving KIMYRSA and warfarin). 7.2 Drug-Laboratory Test Interactions Prolongation of Certain Laboratory Coagulation Tests KIMYRSA may artificially prolong certain laboratory coagulation tests (see Table 2 ) by binding to and preventing the action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests [see Contraindications (4.1) and Warnings and Precautions (5.1 , 5.5) ] . For patients who require monitoring of anticoagulation effect within the indicated time after 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. Oritavancin does not interfere with coagulation in vivo. In addition, oritavancin does not affect tests that are used for diagnosis of Heparin Induced Thrombocytopenia (HIT). Table 2: Coagulation Tests Affected and Unaffected by Oritavancin Elevated by Oritavancin Unaffected by Oritavancin Prothrombin time (PT) up to 12 hours Chromogenic Factor Xa Assay International normalized ratio (INR) up to 12 hours Thrombin Time (TT) Activated partial thromboplastin time (aPTT) up to 120 hours Activated clotting time (ACT) up to 24 hours Silica clot time (SCT) up to 18 hours Dilute Russell's viper venom time (DRVVT) up to 72 hours D-dimer up to 72 hours Positive Indirect and Direct Antiglobulin Tests (IAT/DAT) Positive IAT/DAT were noted with administration of oritavancin products, including KIMYRSA, in studies with healthy volunteers and patients with ABSSSI. Positive IAT may interfere with cross-matching before blood transfusion [see Clinical Pharmacology (12.6) ] .