zoliflodacin 3000 MG Granules for Oral Suspension

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 bacteria. ( 1.2 ) 1.1 Uncomplicated Urogenital Gonorrhea NUZOLVENCE is 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 [see Clinical Studies (14) ]. 1.2 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 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 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 , 2.4 ) Adults and pediatric patients 12 years of age and older, weighing at least 35 kg: Recommended dose is 3 g (one packet) administered as a single dose orally. ( 2.3 ) Patients weighing 35 kg to less than 50 kg: Administer NUZOLVENCE on an empty stomach, 1 hour before or 2 hours after food. ( 2.3 ) Patients weighing greater than or equal to 50 kg: Administer NUZOLVENCE with food. ( 2.3 ) See full prescribing information for complete details on preparation and administration of NUZOLVENCE. ( 2.4 ) 2.1 Pregnancy Testing in Females of Reproductive Potential Obtain a pregnancy test in females of reproductive potential prior to initiating treatment with NUZOLVENCE [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1 , 8.3) ]. 2.2 Important Administration Instructions NUZOLVENCE must be mixed with water before administering. Do not mix NUZOLVENCE with other liquids or sprinkle on food. Do not take NUZOLVENCE in the dry form. 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 [see Dosage and Administration (2.4) ] . 2.3 Recommended Dosage in Adults and Pediatric Patients 12 Years of Age and Older Weighing at Least 35 Kg The recommended dose of NUZOLVENCE in adults and pediatric patients 12 years of age and older weighing at least 35 kg is 3 grams (g) (one packet) administered as a single dose orally. See Table 1 for instructions on whether to administer NUZOLVENCE with or without food based on body weight [see Clinical Pharmacology (12.3) ] . Table 1: Administration of NUZOLVENCE With or Without Food Based on Weight Dose of NUZOLVENCE Body Weight (kg) Administration of NUZOLVENCE Relative to the Ingestion of Food 3 g administered as a single, oral dose 35 kg to less than 50 kg Take on an empty stomach, 1 hour before or 2 hours after food Greater than or equal to 50 kg Take with food 2.4 Preparation and Administration Instructions for NUZOLVENCE for Oral Suspension NUZOLVENCE must be mixed with water before administering. Do not mix NUZOLVENCE with other liquids or sprinkle on food. Accurately measure 60 mL of water into the provided mixing container. Add the entire contents of one unit-dose packet of NUZOLVENCE to the mixing container and immediately secure the provided lid onto the mixing container. Shake vigorously for at least 60 seconds. Continue to shake until all granules are suspended and there is a uniform suspension. Once NUZOLVENCE is mixed to achieve a uniform suspension, administer the entire contents of the mixing container immediately. To ensure the full dose of NUZOLVENCE is consumed, add an additional 60 mL of water to the same mixing container, shake, and administer the entire additional 60 mL of water. 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. See the Instructions for Use for additional details on the preparation and administration of NUZOLVENCE for oral suspension.

WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity: Potential Risk for Pregnant Females: May cause fetal harm when administered during pregnancy based on data from animal studies. Advise pregnant females about the potential risk to the fetus with maternal exposure to NUZOLVENCE. Avoid use of NUZOLVENCE during pregnancy. ( 5.1 , 8.1 , 8.3 ) Embryo-Fetal Toxicity: Potential Risk Related to Males with Female Partners of Reproductive Potential: Advise males with female partners of reproductive potential to use effective contraception for at least 3 months after administration of NUZOLVENCE. ( 5.2 , 8.3 , 13.1 ) Testicular Toxicity and Risks to Male Fertility: May cause testicular toxicity and impair male fertility based on data from animal studies. An assessment of spermatogenesis has not been conducted in humans. Advise males of the potential risk. ( 5.3 , 8.3 , 13.1 ) Hypersensitivity Reactions: Hypersensitivity reactions, including rash and pruritus, have been reported in patients receiving NUZOLVENCE. Discontinue NUZOLVENCE and institute appropriate supportive measures, if an allergic reaction occurs. ( 5.4 ) Clostridioides difficile Infection: Evaluate if diarrhea occurs. ( 5.5 ) 5.1 Embryo-Fetal Toxicity: Potential Risk for Pregnant Females Based on data from animal studies, NUZOLVENCE may cause fetal harm when administered to a pregnant female at clinically relevant doses. Reproductive and developmental toxicity studies at AUC exposures 1.6-fold (mice) and 8.5-fold (rats) the maximum recommended human dose (MRHD) of zoliflodacin administered to pregnant rodents during organogenesis resulted in fetal malformations (exencephaly) and increased embryo-fetal loss [see Use in Specific Populations (8.1) ] . Advise pregnant females about the potential risk to the fetus with maternal exposure to NUZOLVENCE. Avoid use of NUZOLVENCE during pregnancy. Obtain a pregnancy test prior to initiation of treatment with NUZOLVENCE in females of reproductive potential [see Dosage and Administration (2.1) and Use in Specific Populations (8.1 , 8.3) ] . 5.2 Embryo-Fetal Toxicity: Potential Risk Related to Males with Female Partners of Reproductive Potential Based on data from an animal toxicity study, the risk of early pregnancy loss may be increased in female partners of males treated with NUZOLVENCE. A reduced number of live embryos and increased number of embryonic losses were observed in untreated female rats mated with male rats administered zoliflodacin at exposures approximately 3.9-times the clinical exposure at the MRHD for 4 weeks . Advise males with female partners of reproductive potential to use effective contraception for at least 3 months after administration of NUZOLVENCE. [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1) ]. 5.3 Testicular Toxicity and Risks to Male Fertility Based on findings from animal studies, NUZOLVENCE may cause testicular toxicity and impair male fertility. In repeat-dose toxicity studies, rats and dogs administered zoliflodacin for durations of 2 days to 4 weeks at AUC exposures 3- to 11-times the MRHD experienced minimal to moderate decreased spermatogenesis and testicular histopathological changes. In rats, loss of male rat fertility was no longer observed 4 weeks after the last dose; however, testicular histopathological changes in rats and dogs were only partially reversible after 2 to 3 months [see Nonclinical Toxicology (13.1) ] . An evaluation of spermatogenesis has not been conducted in humans. Advise males that NUZOLVENCE may cause testicular toxicity and impair male fertility [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1) ] . 5.4 Hypersensitivity Reactions Hypersensitivity reactions, including rash and pruritus, have been reported in patients receiving NUZOLVENCE [see Adverse Reactions (6.1) ]. NUZOLVENCE is contraindicated in patients with a known history of hypersensitivity to NUZOLVENCE [see Contraindications (4) ] . Before therapy with NUZOLVENCE is instituted, carefully inquire about previous hypersensitivity reactions to NUZOLVENCE. If an allergic reaction to NUZOLVENCE occurs, institute appropriate supportive measures. 5.5 Clostridioides difficile Infection Clostridioides difficile infection (CDI) has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDI. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDI must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDI has been reported to occur over two months after the administration of antibacterial agents. If CDI is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated. 5.6 Development of Drug-Resistant Bacteria Prescribing NUZOLVENCE in the absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see Indications and Usage (1.2) ].

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. ( 4 ) Concomitant use with moderate or strong CYP3A4 inducers because this is predicted to result in decreased plasma concentrations of zoliflodacin and may reduce NUZOLVENCE efficacy. ( 4 , 7.1 )

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