nuzolvence

Important safety information

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) ].