NUZOLVENCE
Generic: ZOLIFLODACIN
Basic Information
Manufacturer
La Jolla Pharmaceutical Company
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
4beda35a-21b0-4b34-84ea-be6ea8cae50f
Indications & Usage
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 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.
( 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.
Adverse Reactions
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.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
A total of 782 patients received a 3 g dose of zoliflodacin across all phases of clinical trials.
The safety of NUZOLVENCE was evaluated in a phase 3, randomized, open-label, active-controlled, multicenter, multinational trial (NCT03959527) (Trial 1).
In total, 927 patients with suspected uncomplicated gonorrhea due to N.
gonorrhoeae were randomized (2:1) and treated with either a single oral 3 g dose of NUZOLVENCE (N=619) or a combination of a single 500 mg intramuscular dose of ceftriaxone and a single 1 g oral dose of azithromycin (N=308) [see Clinical Studies (14) ] .
Patients were eligible for enrollment if they were ≥12 years old and ≥35 kg.
The majority (98%) of patients were adults (≥18 years); 14 patients were 15 to 18 years old: 12/619 (1.9%) in the NUZOLVENCE arm and 2/308 (0.6%) in the ceftriaxone and azithromycin arm.
South Africa had the highest proportion of enrolled patients (46%), followed by Thailand (29%), the United States (17%), and the European Union (8%).
The majority of patients treated with NUZOLVENCE were male (88%).
Patients identified as Black or African American (56%), Asian (31%), White (11%), American Indian or Alaska Native (1%), or Other (1%).
A total of 3% of patients treated with NUZOLVENCE identified as Hispanic or Latino and 22% were living with Human Immunodeficiency Virus (HIV).
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation: There were no serious adverse reactions or adverse reactions leading to treatment discontinuation or death.
Common Adverse Reactions: Table 2 lists adverse reactions occurring in ≥2% of patients receiving NUZOLVENCE in Trial 1.
Table 2: Adverse Reactions in ≥2% of Patients with Suspected Uncomplicated Gonorrhea Infection Treated with NUZOLVENCE in Trial 1 Trial 1 was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the NUZOLVENCE and the ceftriaxone and azithromycin treatment groups.
The safety population includes patients with urogenital gonorrhea as well as those with uncomplicated gonorrhea infections at other body sites not covered under the approved indication.
(Safety Population) Adverse Reaction NUZOLVENCE N = 619 n (%) Ceftriaxone and Azithromycin N = 308 n (%) N, total number of patients in treatment arm; n, number of patients meeting criteria.
Headache Headache includes tension headache and headache.
61 (10) 15 (5) Dizziness 21 (3) 5 (2) Nausea 16 (3) 12 (4) Diarrhea 15 (2) 22 (7) Headache : In Trial 1, headache was reported in 61/619 (10%) of patients receiving NUZOLVENCE; headache severity was mild in 8% of patients and moderate in 2%.
Laboratory Abnormalities Laboratory abnormalities that occurred at a frequency of 2% or greater in Trial 1 are provided in Table 3.
Table 3: Laboratory Abnormalities in ≥2% of Patients with Suspected Uncomplicated Gonorrhea Infection Treated with NUZOLVENCE, with Normal Baseline Values in Trial 1 Trial 1 was not designed to evaluate meaningful comparisons of the incidence of laboratory changes in the NUZOLVENCE and the ceftriaxone and azithromycin treatment groups.
The safety population includes patients with urogenital gonorrhea as well as those with uncomplicated gonorrhea infections at other body sites not covered under the approved indication.
(Safety Population) Laboratory Parameters NUZOLVENCE N = 609 n (%) Ceftriaxone and Azithromycin N = 304 n (%) N, total number of patients in treatment arm with normal baseline values; n, number of patients meeting criteria.
Neutropenia Neutropenia is defined as neutrophil count less than 1500 cells/µL.
71 (12) 43 (14) <1500 to 1000 cells/µL 56 (9) 31 (10) <1000 to 500 cells/µL 14 (2) 12 (4) <500 cells/µL 1 (0.2) 0 Leukopenia Leukopenia is defined as white blood cell count less than 3500 cells/µL.
54 (9) 33 (11) <3500 to 3000 cells/µL 34 (6) 20 (7) <3000 to 1000 cells/µL 20 (3) 13 (4) <1000 cells/µL 0 0 Neutropenia: In Trial 1, 41/609 (7%) and 30/609 (5%) patients developed neutropenia from 4 to 8 days and from 27 to 33 days following NUZOLVENCE administration, respectively.
Of these 71 patients, 25% were living with HIV and 8% had unknown HIV status.
No patients required treatment for neutropenia.
Leukopenia: In Trial 1, 54/609 (9%) of patients developed leukopenia following NUZOLVENCE administration; 16% of these patients were living with HIV and 11% had unknown HIV status.
No patients required treatment for leukopenia.
Other Adverse Reactions Associated with NUZOLVENCE in Trial 1 Adverse reactions occurring in less than 2% of patients receiving NUZOLVENCE in Trial 1 (Safety Population), are presented below: Blood and lymphatic system disorders: Thrombocytopenia, monocyte count decreased, hemoglobin decreased Cardiac disorders: Palpitations Gastrointestinal disorders: Vomiting, abdominal pain, constipation, abdominal distension, flatulence General disorders : Asthenia, fatigue, malaise, pyrexia, chills, feeling hot, night sweats Hepatobiliary disorders : Alanine aminotransferase increased, blood bilirubin increased Infections and infestations : Tinea infections, candidal infections Musculoskeletal and connective tissue disorders: Musculoskeletal pain Nervous system disorders: Somnolence, hypersomnia, hypoesthesia Psychiatric disorders: Insomnia Renal and urinary disorders: Hematuria, blood creatinine increased, glomerular filtration rate decreased Respiratory, thoracic, and mediastinal disorders: Cough Skin and subcutaneous tissue disorders: Rash, pruritus, alopecia, eyelid swelling Vascular disorders: Hot flush
( 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.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
A total of 782 patients received a 3 g dose of zoliflodacin across all phases of clinical trials.
The safety of NUZOLVENCE was evaluated in a phase 3, randomized, open-label, active-controlled, multicenter, multinational trial (NCT03959527) (Trial 1).
In total, 927 patients with suspected uncomplicated gonorrhea due to N.
gonorrhoeae were randomized (2:1) and treated with either a single oral 3 g dose of NUZOLVENCE (N=619) or a combination of a single 500 mg intramuscular dose of ceftriaxone and a single 1 g oral dose of azithromycin (N=308) [see Clinical Studies (14) ] .
Patients were eligible for enrollment if they were ≥12 years old and ≥35 kg.
The majority (98%) of patients were adults (≥18 years); 14 patients were 15 to 18 years old: 12/619 (1.9%) in the NUZOLVENCE arm and 2/308 (0.6%) in the ceftriaxone and azithromycin arm.
South Africa had the highest proportion of enrolled patients (46%), followed by Thailand (29%), the United States (17%), and the European Union (8%).
The majority of patients treated with NUZOLVENCE were male (88%).
Patients identified as Black or African American (56%), Asian (31%), White (11%), American Indian or Alaska Native (1%), or Other (1%).
A total of 3% of patients treated with NUZOLVENCE identified as Hispanic or Latino and 22% were living with Human Immunodeficiency Virus (HIV).
Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation: There were no serious adverse reactions or adverse reactions leading to treatment discontinuation or death.
Common Adverse Reactions: Table 2 lists adverse reactions occurring in ≥2% of patients receiving NUZOLVENCE in Trial 1.
Table 2: Adverse Reactions in ≥2% of Patients with Suspected Uncomplicated Gonorrhea Infection Treated with NUZOLVENCE in Trial 1 Trial 1 was not designed to evaluate meaningful comparisons of the incidence of adverse reactions in the NUZOLVENCE and the ceftriaxone and azithromycin treatment groups.
The safety population includes patients with urogenital gonorrhea as well as those with uncomplicated gonorrhea infections at other body sites not covered under the approved indication.
(Safety Population) Adverse Reaction NUZOLVENCE N = 619 n (%) Ceftriaxone and Azithromycin N = 308 n (%) N, total number of patients in treatment arm; n, number of patients meeting criteria.
Headache Headache includes tension headache and headache.
61 (10) 15 (5) Dizziness 21 (3) 5 (2) Nausea 16 (3) 12 (4) Diarrhea 15 (2) 22 (7) Headache : In Trial 1, headache was reported in 61/619 (10%) of patients receiving NUZOLVENCE; headache severity was mild in 8% of patients and moderate in 2%.
Laboratory Abnormalities Laboratory abnormalities that occurred at a frequency of 2% or greater in Trial 1 are provided in Table 3.
Table 3: Laboratory Abnormalities in ≥2% of Patients with Suspected Uncomplicated Gonorrhea Infection Treated with NUZOLVENCE, with Normal Baseline Values in Trial 1 Trial 1 was not designed to evaluate meaningful comparisons of the incidence of laboratory changes in the NUZOLVENCE and the ceftriaxone and azithromycin treatment groups.
The safety population includes patients with urogenital gonorrhea as well as those with uncomplicated gonorrhea infections at other body sites not covered under the approved indication.
(Safety Population) Laboratory Parameters NUZOLVENCE N = 609 n (%) Ceftriaxone and Azithromycin N = 304 n (%) N, total number of patients in treatment arm with normal baseline values; n, number of patients meeting criteria.
Neutropenia Neutropenia is defined as neutrophil count less than 1500 cells/µL.
71 (12) 43 (14) <1500 to 1000 cells/µL 56 (9) 31 (10) <1000 to 500 cells/µL 14 (2) 12 (4) <500 cells/µL 1 (0.2) 0 Leukopenia Leukopenia is defined as white blood cell count less than 3500 cells/µL.
54 (9) 33 (11) <3500 to 3000 cells/µL 34 (6) 20 (7) <3000 to 1000 cells/µL 20 (3) 13 (4) <1000 cells/µL 0 0 Neutropenia: In Trial 1, 41/609 (7%) and 30/609 (5%) patients developed neutropenia from 4 to 8 days and from 27 to 33 days following NUZOLVENCE administration, respectively.
Of these 71 patients, 25% were living with HIV and 8% had unknown HIV status.
No patients required treatment for neutropenia.
Leukopenia: In Trial 1, 54/609 (9%) of patients developed leukopenia following NUZOLVENCE administration; 16% of these patients were living with HIV and 11% had unknown HIV status.
No patients required treatment for leukopenia.
Other Adverse Reactions Associated with NUZOLVENCE in Trial 1 Adverse reactions occurring in less than 2% of patients receiving NUZOLVENCE in Trial 1 (Safety Population), are presented below: Blood and lymphatic system disorders: Thrombocytopenia, monocyte count decreased, hemoglobin decreased Cardiac disorders: Palpitations Gastrointestinal disorders: Vomiting, abdominal pain, constipation, abdominal distension, flatulence General disorders : Asthenia, fatigue, malaise, pyrexia, chills, feeling hot, night sweats Hepatobiliary disorders : Alanine aminotransferase increased, blood bilirubin increased Infections and infestations : Tinea infections, candidal infections Musculoskeletal and connective tissue disorders: Musculoskeletal pain Nervous system disorders: Somnolence, hypersomnia, hypoesthesia Psychiatric disorders: Insomnia Renal and urinary disorders: Hematuria, blood creatinine increased, glomerular filtration rate decreased Respiratory, thoracic, and mediastinal disorders: Cough Skin and subcutaneous tissue disorders: Rash, pruritus, alopecia, eyelid swelling Vascular disorders: Hot flush