FDA APPROVES TWO NEW ORAL TREATMENTS FOR GONORRHEA
January 2026
The FDA recently approved two new oral antibiotics for the treatment of uncomplicated urogenital gonorrhea: zoliflodacin (Nuzolvence®) and gepotidacin (Blujepa®). These approvals represent significant advances in gonorrhea treatment, as resistance to current therapies, including ceftriaxone and azithromycin, continues to increase worldwide. Both drugs offer oral alternatives to injectable ceftriaxone, potentially improving treatment access and patient convenience. The approvals come at a critical time, as the Centers for Disease Control and Prevention declared antimicrobial-resistant Neisseria gonorrhoeae an urgent public health threat in 2019.
In a phase 3, randomized, controlled, open-label, non-inferiority trial (N=930), zoliflodacin demonstrated microbiological cure rates of 90.9% (95% CI 88.1–93.3) compared with 96.2% (95% CI 92.9–98.3) for ceftriaxone plus azithromycin. The treatment difference was 5.3% (95% CI 1.4–8.6), meeting the prespecified non-inferiority margin of less than 12%. The gepotidacin trial (EAGLE-1), a phase 3, randomized, open-label, sponsor-blinded, multicentre, non-inferiority study (N=628), showed microbiological success rates of 92.6% (95% CI 88.0 to 95.8) for gepotidacin versus 91.2% (95% CI 86.4 to 94.7) for ceftriaxone plus azithromycin, with an adjusted treatment difference of -0.1% (95% CI -5.6 to 5.5), also meeting non-inferiority criteria. Both drugs were generally well tolerated, with most adverse events being mild or moderate in severity.
Gepotidacin was recently approved by the FDA for the treatment of uncomplicated urinary tract infections in females, and its gonorrhea indication expands its clinical utility. Zoliflodacin, while FDA-approved, is not yet available in pharmacies as of early 2026. Zoliflodacin is administered as a single 3 g oral dose (mixed with water as an oral suspension), with dosing instructions based on body weight: patients weighing 77 lbs to less than 110 lbs (35 kg to less than 50 kg) should take it on an empty stomach, while those weighing ≥110 lbs (50 kg) should take it with food. Gepotidacin is given as two 3000 mg doses (four 750 mg tablets each) taken approximately 12 hours apart, and should be administered after a meal. Both drugs work on the same bacterial enzymes (DNA gyrase and topoisomerase IV), but they come from different chemical classes: gepotidacin is a triazaacenaphthylene antibacterial, while zoliflodacin is a spiropyrimidinetrione antibacterial. Due to animal studies showing potential fetal harm, zoliflodacin should not be given to pregnant women, and males with female partners of reproductive potential should use effective contraception for at least 3 months after administration. Common side effects of zoliflodacin include neutropenia (7%), headache (10%), leukopenia (4%), dizziness (3%), nausea (3%), and diarrhea (2%). Gepotidacin’s most common adverse reactions include diarrhea (49%), nausea (24%), abdominal pain (15%), vomiting (12%), flatulence (10%), dizziness (8%), soft feces (8%), headache (7%), fatigue (6%), and hyperhidrosis (6%). Both drugs have important drug interactions: zoliflodacin is contraindicated with moderate or strong CYP3A4 inducers, while gepotidacin should not be used with strong CYP3A4 inhibitors and should be avoided with moderate CYP3A4 inhibitors in gonorrhea patients.
