Drug Update · Infectious Disease

FDA Approves zoliflodacin for Uncomplicated Urogenital Gonorrhea: 90.9% Microbiologic Cure

August 20, 2026

Approved indication

Uncomplicated urogenital gonorrhea in adults and pediatric patients ≥12 years and ≥35 kg [1][2]

Primary efficacy (micro-ITT urogenital)

NUZOLVENCE 460/506 (90.9%) vs ceftriaxone + azithromycin 229/238 (96.2%); difference -5.3 (95% CI -8.7, -1.4) [1][10]

Recommended dose

3 g (one packet) single oral dose administered as oral suspension [1]

Pivotal trial

Phase 3 randomized, open-label, active-controlled Trial 1 (NCT03959527); 930 randomized, 2:1 [1][10]

FDA approval date

December 12, 2025 (approval letter and press announcement) [2][4]

Clinical Perspective

Infectious disease clinicians, sexual health specialists, and primary care clinicians treating adults and adolescents 12 years and older (≥35 kg) with uncomplicated urogenital gonorrhea now have an FDA-approved oral option, NUZOLVENCE, available as a single 3 g oral dose ^[1]^[2]. The approval is supported by Trial 1 showing microbiological cure 460/506 (90.9%) with NUZOLVENCE versus 229/238 (96.2%) with ceftriaxone plus azithromycin in the micro-ITT urogenital population, demonstrating non-inferiority ^[1]^[5]. How postmarketing surveillance will track resistance emergence, embryo-fetal and reproductive toxicity signals specified as required postmarketing studies will inform longer-term safety and stewardship strategies for use of NUZOLVENCE?

Dr. Simran Kohli, MBBS, MD (General Medicine), DM (Infectious Diseases) · Infectious Diseases

The FDA approved NUZOLVENCE (zoliflodacin) 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 on December 12, 2025, based on a phase 3 randomized trial (NCT03959527; Trial 1) in which NUZOLVENCE achieved microbiological cure in 460/506 (90.9%) versus 229/238 (96.2%) with ceftriaxone plus azithromycin at the urogenital test-of-cure visit (Day 4 to 8) ^[2]^[1]^[5]. Clinicians should consult current prescribing information for complete dosing guidance.

Clinical Context

NUZOLVENCE (zoliflodacin) is described in the prescribing information as a spiropyrimidinetrione bacterial type II topoisomerase inhibitor indicated for uncomplicated urogenital gonorrhea in adults and pediatric patients 12 years and older weighing at least 35 kg ^[1]. The product is supplied as a 3 g unit-dose packet of granules for oral suspension that must be mixed with water prior to administration ^[1]. The NDA was submitted by Entasis Therapeutics, Inc., and the FDA completed review and approved the application in December 2025 ^[2]^[3]. The FDA press announcement noted testing against a comparator regimen of intramuscular ceftriaxone plus oral azithromycin in the pivotal study and framed approval in the context of rising gonococcal drug resistance ^[4].

Key Findings

In the phase 3 randomized, open-label, active-controlled Trial 1 (NCT03959527), NUZOLVENCE achieved microbiological cure at the urogenital site in 460/506 (90.9%) versus 229/238 (96.2%) with a single IM 500 mg dose of ceftriaxone plus a single 1 g oral dose of azithromycin in the micro-ITT urogenital population; the trial demonstrated non-inferiority of NUZOLVENCE to ceftriaxone plus azithromycin ^[1]^[5]^[3].
Clinicians should consult current prescribing information for full dosing guidance.
Trial 1 enrolled a total of 930 patients randomized 2:1 to NUZOLVENCE (N=619) or ceftriaxone plus azithromycin (N=308); the micro-ITT urogenital population used for the primary analysis comprised 744 patients (506 NUZOLVENCE; 238 comparator) ^[1]^[5].
The primary endpoint was microbiological cure (confirmed bacterial eradication of N. gonorrhoeae at the urogenital site) assessed at the test-of-cure visit on Day 4 to 8 after treatment ^[1]^[5].

Safety & Tolerability

Neutropenia (laboratory abnormality reported in Trial 1) ^[1].
Headache (61/619; 10% in NUZOLVENCE-treated patients in Trial 1) ^[1].
Leukopenia (laboratory abnormality reported in Trial 1) ^[1].
Dizziness (21/619; 3% in NUZOLVENCE-treated patients in Trial 1) ^[1].
Nausea (16/619; 3% in NUZOLVENCE-treated patients in Trial 1) ^[1].
Diarrhea (15/619; 2% in NUZOLVENCE-treated patients in Trial 1) ^[1].
Embryo-fetal toxicity: potential risk for pregnant females based on animal data; advise pregnant females and avoid use during pregnancy ^[1].
Testicular toxicity and potential impairment of male fertility based on animal data; advise males of reproductive potential about potential risk ^[1].
Hypersensitivity reactions, including rash and pruritus, have been reported ^[1].
Clostridioides difficile infection: evaluate if diarrhea occurs ^[1].
Development of drug-resistant bacteria: guidance to use NUZOLVENCE only to treat or prevent infections proven or strongly suspected to be caused by susceptible bacteria ^[1].

Study Design

Trial 1 (NCT03959527) was a phase 3, randomized, open-label, active-controlled, multicenter, multinational trial that randomized 930 patients with suspected uncomplicated gonorrhea 2:1 to a single oral 3 g dose of NUZOLVENCE (N=619) or a single IM 500 mg dose of ceftriaxone plus a single 1 g oral dose of azithromycin (N=308); the primary analysis population for the urogenital endpoint was the micro-ITT urogenital population (N=744: 506 NUZOLVENCE; 238 comparator) and the primary endpoint was microbiological cure at the urogenital test-of-cure visit (Day 4 to 8) ^[1]^[5]^[3]. Clinicians should consult current prescribing information for full dosing guidance.

FAQ

Q1 What is NUZOLVENCE approved for?

NUZOLVENCE (zoliflodacin) is approved 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, per the FDA-approved indication in the prescribing information and approval documents. The approval is for single-dose oral administration as specified in the labeling.

Q2 How does zoliflodacin work?

Zoliflodacin is described in the prescribing information as a spiropyrimidinetrione bacterial type II topoisomerase inhibitor. The prescribing information identifies its mechanism as a bacterial type II topoisomerase inhibitor and provides microbiology and clinical pharmacology sections that informed its regulatory review and approval.

Q3 What is the recommended dose of NUZOLVENCE?

The recommended dose for adults and pediatric patients 12 years of age and older weighing at least 35 kg is 3 grams (one unit-dose packet) administered as a single oral dose. The product is supplied as granules for oral suspension that must be mixed with 60 mL of water in the provided container and administered within 15 minutes of mixing; instructions vary by weight regarding administration with or without food. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of NUZOLVENCE?

The most common adverse reactions and laboratory abnormalities reported in the pivotal trial (incidence ≥2%) included neutropenia, headache, leukopenia, dizziness, nausea, and diarrhea. The prescribing information also identifies warnings and precautions including embryo-fetal toxicity (animal data), potential testicular toxicity and effects on male fertility (animal data), hypersensitivity reactions (including rash and pruritus), Clostridioides difficile infection risk with antibacterial use, and the potential for development of drug-resistant bacteria. For comprehensive safety information, consult the full prescribing information.

Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves zoliflodacin for Uncomplicated Urogenital Gonorrhea: 90.9% Microbiologic Cure

Direct Clinical Takeaway & Evidence Summary

FDA Approves zoliflodacin for Uncomplicated Urogenital Gonorrhea: 90.9% Microbiologic Cure

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Get weekly clinical updates for Infectious Disease in your inbox.

Related Clinical Updates

FDA Approves doravirine/islatravir for Virologically Suppressed HIV‑1: 1% ≥50 copies/mL

REVIVE: Fluvoxamine Reduces Fatigue Severity (−0.43 FSS) vs Placebo

Nirmatrelvir/Ritonavir Cuts Hospitalization Risk 89% in EPIC-HR

Verified HCP Portal