Overview
11 DESCRIPTION KIMYRSA (oritavancin) for injection contains oritavancin diphosphate, a semisynthetic lipoglycopeptide antibacterial drug for intravenous infusion. The chemical name for oritavancin is [4"R]-22- O -(3-amino-2,3,6-trideoxy-3- C -methyl-α-L- arabino -hexopyranosyl)- N 3''-[(4'-chloro[1,1'-biphenyl]-4-yl)methyl] vancomycin phosphate [1:2] [salt].
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Oritavancin is an antibacterial drug [see Microbiology (12.4) ] . 12.2 Pharmacodynamics The antimicrobial activity of oritavancin appears to correlate with the ratio of area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) based on animal models of infection. The AUC from time zero to 72 hours correlates with antimicrobial activity in both preclinical and clinical studies. Exposure-response analyses from both preclinical and clinical studies support the treatment of clinically relevant gram-positive microorganisms (e.g. S. aureus and S. pyogenes ) causative of ABSSSI with a single 1,200 mg dose of oritavancin. Cardiac Electrophysiology In a thorough QTc study of 135 healthy subjects at a dose 1.
Indications
- 1 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.
Common Doses
- 200 mg
- 40 mL
- 30 mg
- 250 mL
Dosage
2 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.
Contraindications
- 4 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.
Side Effects
- 6 ADVERSE REACTIONS 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.
Interactions
- 7 DRUG INTERACTIONS 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.