Drug Update · Infectious Disease

FDA Approves zoliflodacin for Gonorrhea: 90.9% Cure Rate

July 16, 2026

Primary efficacy (micro-ITT urogenital)

NUZOLVENCE 460/506 (90.9%) vs ceftriaxone+azithromycin 229/238 (96.2%) [11]

Trial

Trial 1 (NCT03959527), randomized 2:1, 930 patients [11]

Comparator

Intramuscular ceftriaxone 500 mg + oral azithromycin 1 g [11][10]

Approved indication

Uncomplicated urogenital gonorrhea in adults and pediatric patients ≥12 years and ≥35 kg [11]

Approved date / label effective

FDA approval December 12, 2025; label effective 2025-12-22 [11][10]

Clinical Perspective

Clinicians treating patients with uncomplicated urogenital gonorrhea—adults and pediatric patients aged ≥12 years and weighing at least 35 kg—have a newly approved oral option with NUZOLVENCE ^[3]^[2]. The randomized trial data support NUZOLVENCE as an oral, single-dose treatment alternative compared with a single intramuscular ceftriaxone plus oral azithromycin regimen for microbiological cure at Day 4 to Day 8 ^[3]^[2]. gonorrhoeae susceptibility and emerging resistance will affect the durability and positioning of zoliflodacin relative to ceftriaxone-based therapy?

Dr. Simran Kohli · Infectious Diseases

The FDA approved zoliflodacin (NUZOLVENCE) for the treatment of uncomplicated urogenital gonorrhea in adults and pediatric patients 12 years and older weighing at least 35 kg based on Trial 1 (NCT03959527), which showed microbiological cure rates of 90.9% (460/506) with zoliflodacin versus 96.2% (229/238) with intramuscular ceftriaxone plus oral azithromycin in the micro-ITT urogenital population ^[3]^[2]. The approval was granted in December 2025 with labeling and administration instructions on oral suspension preparation and weight-based food administration guidance ^[3].

Clinical Context

Zoliflodacin (NUZOLVENCE) is a spiropyrimidinetrione antibacterial that inhibits bacterial type II topoisomerases and is developed for oral treatment of uncomplicated urogenital gonorrhea due to Neisseria gonorrhoeae ^[3]. The product is supplied as granules for oral suspension; the labeler listed in DailyMed is Dr. Reddy’s Laboratories, Inc. (marketing start 02/01/2026) and DailyMed posting reflects the drug information and packaging details ^[1]. The FDA approval arrives as guidance and investigators note rising gonococcal antimicrobial resistance; the pivotal randomized trial compared a single 3 g oral dose of zoliflodacin to the then-standard single intramuscular ceftriaxone 500 mg plus single oral azithromycin 1 g regimen ^[2]^[3]. Clinicians should consult current prescribing information for full dosing guidance. Prescribing information specifies preparation, administration, and a pregnancy-testing requirement for females of reproductive potential prior to dosing ^[3].

Key Findings

Trial 1 (NCT03959527) showed NUZOLVENCE achieved microbiological cure of 90.9% (460/506) versus 96.2% (229/238) with ceftriaxone plus azithromycin in the micro-ITT urogenital population (difference -5.3; 95% CI -8.7, -1.4), demonstrating non-inferiority in the trial’s primary endpoint ^[3].
The randomized, open-label, active-controlled multicenter multinational study enrolled 930 patients randomized 2:1 to NUZOLVENCE or ceftriaxone plus azithromycin, and evaluated bacterial eradication at a test-of-cure visit on Day 4 to Day 8 ^[3]^[2].
In the micro-ITT urogenital population demographics reported included 91% male, mean age 30 years (range 16–73), mean weight 70 kg (range 37–139), with racial distribution reported as 55% Black, 31% Asian, 13% White, and 4% Hispanic or Latino ^[3].

Safety & Tolerability

Low white blood cell counts ^[2]^[3]
Headache ^[2]^[3]
Dizziness ^[2]^[3]
Nausea ^[2]^[3]
Diarrhea ^[2]^[3]
Animal studies indicated potential for birth defects, pregnancy loss, and male fertility effects; labeling includes a pregnancy testing recommendation for females of reproductive potential prior to initiating treatment ^[2]^[3]

Study Design

NUZOLVENCE received FDA approval following a randomized, open-label, active-controlled, multicenter, multinational pivotal trial (Trial 1; NCT03959527) that randomized 930 patients 2:1 to a single oral 3 g dose of NUZOLVENCE versus a single intramuscular 500 mg dose of ceftriaxone plus a single 1 g oral dose of azithromycin ^[3]. Clinicians should consult current prescribing information for full dosing guidance. The primary efficacy analysis was microbiological cure at a test-of-cure visit (Day 4 to Day 8) in the micro-ITT urogenital population (744 patients: 506 NUZOLVENCE, 238 ceftriaxone plus azithromycin) ^[3]. The FDA approval for uncomplicated urogenital gonorrhea in adults and pediatric patients 12 years and older weighing at least 35 kg was granted in December 2025 with labeling effective dated December 22, 2025 ^[3]^[2].

FAQ

Q1 What is NUZOLVENCE (zoliflodacin) approved for?

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 who weigh at least 35 kg. The approval and indication are based on the randomized Trial 1 (NCT03959527) evaluating microbiological cure at a test-of-cure visit on Day 4 to Day 8.

Q2 How does zoliflodacin work?

Zoliflodacin is a spiropyrimidinetrione antibacterial that inhibits bacterial type II topoisomerases; its mechanism targets the bacterial topoisomerase II enzymes involved in DNA replication and repair. The prescribing information and microbiology section describe zoliflodacin as a bacterial type II topoisomerase inhibitor developed for oral single-dose therapy in uncomplicated urogenital gonorrhea.

Q3 What is the recommended dose of NUZOLVENCE?

The recommended dose in adults and pediatric patients 12 years and older weighing at least 35 kg is a single oral 3 g dose (one packet) administered as an oral suspension after mixing with water; administration with or without food depends on body weight (35 to <50 kg on an empty stomach 1 hour before or 2 hours after food; ≥50 kg take with food). The label includes preparation and administration steps and requires pregnancy testing in females of reproductive potential prior to dosing. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of zoliflodacin?

In the pivotal study the most commonly reported adverse events included low white blood cell counts, headache, dizziness, nausea, and diarrhea. The FDA and label also note that animal studies showed potential for birth defects, pregnancy loss, and male fertility effects, and the prescribing information requires pregnancy testing in females of reproductive potential prior to treatment.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves zoliflodacin for Gonorrhea: 90.9% Cure Rate

FDA Approves zoliflodacin for Gonorrhea: 90.9% Cure Rate

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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