Overview
11 DESCRIPTION NUZOLVENCE for oral suspension contains zoliflodacin, an oral spiropyrimidinetrione bacterial type II topoisomerase inhibitor. The chemical name of zoliflodacin is (2R,4S,4aS)-11-Fluoro-1,2,4,4a-tetrahydro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-3-oxazolidinyl]spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5(6H),5'(2'H)-pyrimidine]-2',4',6'(1'H,3'H)-trione.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action NUZOLVENCE is an antibacterial drug [see Microbiology (12.4) ] . 12.2 Pharmacodynamics The ratio of the unbound plasma zoliflodacin area under the concentration-time curve from time of dosing extrapolated to infinity to the zoliflodacin MIC ( f AUC 0-inf /MIC) is the best predictor of efficacy based on in vitro models of infection. Cardiac Electrophysiology A thorough QTc study of single oral doses of zoliflodacin 2 g and 4 g (not approved doses of NUZOLVENCE) was conducted in 72 healthy subjects aged 18 to 45 years. A concentration-dependent increase in QTc interval was observed in the thorough QTc study.
Indications
- 1 INDICATIONS AND USAGE NUZOLVENCE is a spiropyrimidinetrione bacterial type II topoisomerase inhibitor indicated for the treatment of uncomplicated urogenital gonorrhea due to Neisseria gonorrhoeae in adults and pediatric patients 12 years of age and older, weighing at least 35 kg. ( 1.1 ) Usage to Reduce Development of Drug-Resistant Bacteria To reduce the development of drug-resistant bacteria and maintain the effectiveness of NUZOLVENCE and other antibacterial drugs, NUZOLVENCE should be used only to treat or prevent infections that are proven or strongly suspected to be caused by...
Common Doses
- 3 g
- 60 mL
Dosage
2 DOSAGE AND ADMINISTRATION Pregnancy Testing: Obtain a pregnancy test in females of reproductive potential prior to initiating NUZOLVENCE. ( 2.1 ) NUZOLVENCE must be mixed with water before administering. ( 2.2 ) Do not mix NUZOLVENCE with other liquids or sprinkle on food. ( 2.2 ) Administer the entire dose within 15 minutes of mixing. If the dose is not administered within 15 minutes of mixing, a new dose of NUZOLVENCE must be prepared. ( 2.2 , 2.
Contraindications
- 4 CONTRAINDICATIONS NUZOLVENCE is contraindicated in: patients with a known history of hypersensitivity to NUZOLVENCE [see Warnings and Precautions (5.4) ] . patients who use concomitant moderate or strong CYP3A4 inducers because concomitant use is predicted to result in decreased plasma concentrations of zoliflodacin and may reduce the efficacy of NUZOLVENCE [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]. Known history of hypersensitivity to NUZOLVENCE.
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in the Warnings and Precautions section of the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] The most common adverse reactions including laboratory abnormalities (incidence ≥2%) with NUZOLVENCE are neutropenia, headache, leukopenia, dizziness, nausea, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Entasis Therapeutics, Inc. at 1-800-651-3861 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS 7.1 Effect of Other Drugs on NUZOLVENCE Moderate and Strong CYP3A4 Inducers Concomitant use of moderate or strong inducers of CYP3A4 with NUZOLVENCE is contraindicated [see Contraindications (4) ] . Zoliflodacin is a CYP3A4 substrate. Moderate and strong CYP3A4 inducers are predicted to result in decreased plasma concentrations of zoliflodacin and may reduce NUZOLVENCE efficacy [see Clinical Pharmacology (12.3) ] .