FDA Approves First New Oral Gonorrhea Treatments in Decades, Offering Alternatives to the Standard Shot

The patient in Exam Room 3 had done this before.

He knew the questions about partners and protection, the nasal swab for COVID to rule out other causes of fever, and, finally, the sting of an antibiotic shot in the hip. For years, that intramuscular injection of ceftriaxone has been the standard treatment in U.S. clinics for gonorrhea, one of the most common sexually transmitted infections in the country.

Soon, that routine may change.

Two new oral options

In mid-December, the Food and Drug Administration approved two new oral antibiotics for uncomplicated urogenital gonorrhea in adolescents and adults, the first time in decades that pills have been cleared in the United States specifically to treat the infection.

On Dec. 11 and 12, the agency signed off on Nuzolvence (zoliflodacin) and a new use for Blujepa (gepotidacin). Both are first-in-class drugs that work differently from existing antibiotics and are aimed at a pathogen that has repeatedly evolved to evade older medicines.

“These approvals mark a significant milestone for treatment options for patients with uncomplicated urogenital gonorrhea,” Dr. Adam Sherwat, who heads the FDA’s Office of Infectious Diseases, said in announcing the decision.

The move comes as public health officials warn that Neisseria gonorrhoeae, the bacterium that causes gonorrhea, is edging toward resistance to ceftriaxone, the last widely effective injectable antibiotic for routine cases.

What the FDA approved

Nuzolvence (zoliflodacin)

Under its new approval, Nuzolvence is indicated for adults and adolescents 12 and older who weigh at least 77 pounds and have uncomplicated urogenital gonorrhea. The drug is supplied as granules that are dissolved in water and taken as a single 3-gram oral dose.

In a late-stage clinical trial of about 930 people, a single dose of zoliflodacin cleared infection in 91% of patients four to eight days after treatment. The standard regimen used in the comparison group—an injection of ceftriaxone followed by an oral dose of azithromycin—cured 96% of patients. The FDA said the new drug’s performance was comparable to the existing standard of care.

Blujepa (gepotidacin)

Blujepa, developed by GSK, is an oral tablet that the FDA first approved in March 2025 to treat uncomplicated urinary tract infections in some female patients. The agency has now expanded its label to include uncomplicated urogenital gonorrhea in patients 12 and older who weigh at least 99 pounds.

The gonorrhea indication for Blujepa is tightly limited. The label specifies that it should be used only in patients “who have limited or no alternative treatment options,” and notes that the approval is based on a smaller safety database for this use than is typical.

In its Phase 3 EAGLE-1 trial, involving about 600 participants with uncomplicated urogenital gonorrhea, patients who received two 3,000-milligram doses of gepotidacin 10 to 12 hours apart had a 93% cure rate. Those who received an injection of ceftriaxone and an oral dose of azithromycin had a 91% cure rate. The study showed that Blujepa was not inferior to the standard regimen.

GSK’s chief scientific officer, Tony Wood, said in a statement that the company was “proud to have delivered the first new class of antibiotics for gonorrhea in over three decades and a new oral option for U.S. patients.”

How they work—and why they matter

Both drugs inhibit bacterial enzymes involved in DNA replication but bind at different sites than fluoroquinolones and cephalosporins, the classes that have dominated treatment in recent decades. Both received priority review and Qualified Infectious Disease Product designations, which speed FDA evaluation and provide extra years of market exclusivity.

While the approvals open the door to pill-based treatment, neither drug is expected to immediately displace ceftriaxone in U.S. guidelines.

The Centers for Disease Control and Prevention’s current sexually transmitted infection treatment guidelines recommend a single intramuscular injection of ceftriaxone—500 milligrams for most patients, or 1 gram for those weighing 300 pounds or more—for uncomplicated infections of the cervix, urethra, rectum or throat. If chlamydia infection has not been ruled out, the CDC advises adding a week-long course of oral doxycycline.

For now, those recommendations remain in place. The CDC has not yet issued updated guidance that reflects the new approvals, a process that typically follows further review of real-world safety and effectiveness.

A growing resistance problem

Gonorrhea remains a major public health problem. The CDC reported 601,319 cases in the United States in 2023, making it the nation’s second most commonly reported notifiable sexually transmitted infection. Globally, the World Health Organization estimates about 82 million new infections are acquired each year.

Over decades, the bacterium has rendered successive drugs unreliable, from sulfonamides and penicillin to tetracyclines, fluoroquinolones and some oral cephalosporins. The WHO lists cephalosporin- and fluoroquinolone-resistant Neisseria gonorrhoeae among its highest-priority pathogens for new antibiotic development.

“Availability of additional treatment options is of particular importance given the global rise in gonococcal drug resistance,” Dr. Peter Kim, who leads the FDA division that reviews anti-infective drugs, said in the agency’s statement.

Easier treatment, new safeguards

The new pills could make treatment easier for some patients.

Because ceftriaxone must be given as an injection, most people with gonorrhea need to visit a clinic or emergency department, which can pose barriers for those with limited transportation, inflexible work schedules or discomfort seeking in-person sexual health care. A single-dose oral regimen like Nuzolvence’s could potentially be prescribed through telehealth and filled at a pharmacy, though how it will be used in practice will depend on coverage, cost and guidance from health authorities.

“Approval of zoliflodacin marks a pivotal moment,” said Dr. David Altarac, chief medical officer at Innoviva Specialty Therapeutics, which now owns Entasis Therapeutics, the original developer. “For the first time in decades, both patients and their healthcare providers will have a single-dose, oral treatment option.”

Zoliflodacin’s path to market also differs from typical antibiotic launches. It was co-developed by Entasis and the Global Antibiotic Research and Development Partnership (GARDP), a nonprofit backed by governments and foundations. Under licensing agreements, Innoviva controls commercialization in high-income markets such as North America and much of Europe, while GARDP has the rights to register and sell the drug in more than 150 low- and middle-income countries.

GARDP has said it will pursue pricing and distribution strategies intended to improve access in countries that often bear a disproportionate share of the global gonorrhea burden but have historically been last to receive new antibiotics.

Gepotidacin followed a more conventional corporate route, but with an unusual funder. Its development has been supported in part by the U.S. Biomedical Advanced Research and Development Authority and the Department of Defense’s Defense Threat Reduction Agency, reflecting interest in having new oral agents available in the event of mass-casualty incidents where bacterial infections surge.

Safety warnings and limits on use

Both drugs carry safety warnings that may shape how widely they are used.

The FDA highlighted animal data suggesting zoliflodacin could affect fetal development and male fertility, and advised caution in people who are pregnant or may become pregnant. Its label also warns of potential decreases in certain white blood cells and lists headache, dizziness, nausea and diarrhea among common adverse reactions.

Gepotidacin’s label notes that the drug can prolong the heart’s QT interval in a dose- and concentration-dependent manner, which can trigger arrhythmias in susceptible individuals. The agency recommends avoiding its use in patients with known QT prolongation, certain cardiac conditions or those taking other QT-prolonging medications. The label also advises against use with strong CYP3A4 inhibitors and in some people with kidney or liver impairment.

Public health experts say those restrictions, along with Blujepa’s “limited or no alternative options” clause, are likely to function as safeguards against overuse. With experience from past decades, officials are wary that widespread, unsupervised use of new oral monotherapies for a common infection could speed the emergence of resistance.

What happens next

How quickly the new drugs will reach patients in the United States is not yet clear. Innoviva has said Nuzolvence is expected to be commercially available in the second half of 2026. GSK has existing supply chains for Blujepa through its urinary tract infection indication, but its gonorrhea label limits the eligible population.

For now, the familiar shot of ceftriaxone remains the backbone of gonorrhea treatment. The two new pills add long-awaited options, but they also sharpen a dilemma that has defined the antibiotic era: how to deploy powerful new drugs widely enough to relieve suffering without using them so freely that they lose their power.