Zoliflodacin

Kathryn Dzintars, Pharm.D., BCPS

INDICATIONS

FDA

  • Zoliflodacin (Nuzolvence®) is approved for the treatment of uncomplicated urogenital gonorrhea due to Neisseria gonorrhoeae in adults and pediatric patients at least 12 years of age and who weigh at least 35 kg.

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

Nuzolvence

Zoliflodacin

Entasis Therapeutics

PO

Unit dose packet for oral suspension

3 g

N/A

*Prices represent the cost per unit specified and are representative of the "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

  • Zolifodacin as 3 g (one packet) as a single oral dose
    • Zoliflodacin must be mixed with water before administration; do NOT mix it with other liquids or sprinkle it on food.
    • Administer the entire dose within 15 minutes of mixing; if the dose is not taken within 15 minutes, a new packet must be mixed.
    • Weight-based recommendations:
      • For patients weighing at least 50 kg, administer with food
      • For patients weighing 35 kg to 50 kg, administer on an empty stomach, 1 hour before or 2 hours after food.

ADULT RENAL DOSING

  • No dosage adjustment is necessary.

DOSING IN HEMODIALYSIS

  • No dosage adjustment is necessary.

PEDIATRIC DOSING

USUAL PEDIATRIC DOSING

  • Zoliflodacin is only approved for pediatric patients at least 12 years of age who weigh at least 35 kg.
    • 3 g (one packet) as a single oral dose
      • Zoliflodacin must be mixed with water before administration; do NOT mix it with other liquids or sprinkle it on food.
      • Administer the entire dose within 15 minutes of mixing; if the dose is not taken within 15 minutes, a new packet must be mixed.
      • For patients weighing at least 50 kg, administer with food.
      • For patients weighing 35 kg to 50 kg, administer on an empty stomach, 1 hour before or 2 hours after food

PEDIATRIC RENAL DOSING

  • No dosage adjustment is necessary.

ADVERSE DRUG REACTIONS

GENERAL

  • Zoliflodacin is generally well-tolerated, but allergic reactions (rash and pruritus) are possible.

COMMON

  • Headache (10%)
  • Neutropenia (12%), although this adverse effect rate was similar to that reported with the combination of ceftriaxone/azithromycin (14%)

DRUG INTERACTIONS

  • Avoid the concomitant use of moderate-to-strong CYP3A4 inducers with zoliflodacin, as it may result in decreased plasma concentrations.
  • Co-administration with rifampin reduced zoliflodacin exposure by 56%.
Drug-to-Drug Interactions

Drug

Effect of Interaction

Recommendations/Comments

SPECTRUM

Spectrum of Activity

Pathogen

Line

Neisseria gonorrhoeae

2nd

RESISTANCE

  • Mutations in type II topoisomerases, specifically gyrB (D429N, K450N, K450T)
    • Presence of one of these mutations is associated with a 4- to 16-fold increase in zoliflodacin MIC.
    • Prevalence remains low, with no mutations found in a public database of >13,000 isolates.
  • Efflux pumps (MtrCDE, MacAB, NorM)

PHARMACOLOGY

MECHANISM

  • Zoliflodacin is a spiropyrimidinetrione inhibitor of bacterial type II topoisomerases, as it binds within the cleaved DNA-gyrase complex, blocking re-ligation of the gyrase B subunit

PHARMACOKINETIC PARAMETERS

Absorption

  • Absorption is favorable and complete [Tmax h, median (min to max)]
    • Fasted: 2.5 (1.0 - 4.0)
    • Fed: 4.0 (3.0 - 5.5)

Metabolism and Excretion

  • Primary route of administration: fecal (80%)
    • Some metabolism occurs through both CYP-mediated and non-CYP-mediated pathways.

Protein Binding

  • Protein binding: 83%

Cmax, Cmin, and AUC

  • Cmax* (mcg/mL): 28.5 (21.6%)
  • AUC* (h*mcg/mL): 353 (24.1%)

*Geometric mean (%GCV)

T1/2

  • Fasted: 6.4h (20.4)
  • Fed: 5.5h (14.0)

Distribution

  • Vd* (L)
    • Fasted: 177 (26.6)
    • Fed: 98.7 (24.1)

*Geometric mean (%GCV)

DOSING FOR DECREASED HEPATIC FUNCTION

  • No dosage adjustment is necessary.

PREGNANCY RISK

  • Zoliflodacin may cause fetal malformations and/or increased embryo-fetal loss when administered to pregnant females based on animal studies completed in mice at AUC exposures greater than 1.6 times that used in humans.
  • While there are no human data on the use of zoliflodacin during pregnancy, pregnant females should be advised of the risk to the fetus with maternal exposure.
  • All women should have a negative pregnancy test before being prescribed zoliflodacin; males with female partners who could become pregnant should use effective contraception for 90 days after receiving zoliflodacin.

BREAST FEEDING COMPATIBILITY

  • There are no data on the presence of zoliflodacin in either human or animal breastmilk, effects on the breastfed infant, or effects on milk production. Caution should be used if considering zoliflodacin use in the breastfeeding patient.

COMMENTS

  • An estimated 82.4 million cases of gonorrhea globally were reported by the WHO in 2020. It is considered an urgent global health threat as resistance has been demonstrated to every class of antibiotics (cephalosporins, azithromycin, fluoroquinolones) that have been used for its treatment.
  • Urgent need for new antimicrobials againstN. gonorrhoeae; zoliflodacin and gepotidacin are promising.
  • Zoliflodacin was compared to ceftriaxone/azithromycin in a phase 3, multinational, randomized, controlled, open-label, non-inferiority trial in patients at least 12 years of age and older.
    • Trial was completed at 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand and the U.S.
      • Participants were randomized in a 2:1 manner to receive either zoliflodacin 3 g PO x1 (n = 621) dose or ceftriaxone 500 mg IM + azithromycin 1 g orally (n = 309)
      • The primary endpoint was the proportion of patients with microbiologic cure at the test of cure in the ITT population.
      • Microbiologic cure rates at TOC: Zoliflodacin 460/509 (90.9%; 95% CI 88.1 - 93.3) against comparator 229-238 (96.2%; 95% CI 92.9 - 98.3).
      • The estimated difference between groups was 5.3%, meeting the pre-specified non-inferiority margin of less than 12%.
    • Adverse events were similar across groups, with the majority mild to moderate in severity. No serious adverse events were reported.

References

  1. Luckey A, Balasegaram M, Barbee LA, et al. Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial. Lancet. 2025.  [PMID:41391465]

    Comment: Zoliflodacin was compared to ceftriaxone/azithromycin in a phase 3, multinational, randomized, controlled, open-label, non-inferiority trial in patients at least 12 years of age and older. Zoliflodacin 3 g PO as a single dose was non-inferior to the combination of ceftriaxone + azithromycin at the microbiologic test-of-cure visit for the management of gonorrhea. No serious adverse events were reported.

  2. Maatouk I, Vumbugwa P, Cherdtrakulkiat T, et al. Antimicrobial resistance in Neisseria gonorrhoeae in nine sentinel countries within the World Health Organization Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP), 2023: a retrospective observational study. Lancet Reg Health West Pac. 2025;61:101663.  [PMID:40922809]

    Comment: WHO surveillance data, 2020

  3. Raccagni AR, Ranzenigo M, Bruzzesi E, et al. Neisseria gonorrhoeae Antimicrobial Resistance: The Future of Antibiotic Therapy. J Clin Med. 2023;12(24).  [PMID:38137836]

    Comment: Review article discussing the need for novel agents targeting N. gonorrheae.

  4. Adamson PC, Lin EY, Ha SM, et al. Using a public database of Neisseria gonorrhoeae genomes to detect mutations associated with zoliflodacin resistance. J Antimicrob Chemother. 2021;76(11):2847-2849.  [PMID:34324655]

    Comment: Prevalence determination of the three amino acid mutations (D429N, K450N, K450T) associated with zoliflodacin resistance in N. gonorrheae in an extensive public database of nearly 13,000 isolates. No isolates harbored any of the three mutations.

  5. https://innovivaspecialtytherapeutics.com/wp-content/uploads/2025/12/NUZOLVENCE-zoliflodacin-Full-Prescribing-Information-December-2025.pdf (accessed 1/13/2026).

    Comment: Zoliflodacin prescribing information

Last updated: January 17, 2026