Zoliflodacin

Zoliflodacin is a prescription medicine used 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.

Zoliflodacin is available under the following different brand names: Nuzolvence

Common side effects of Zoliflodacin include:

• neutropenia
• headache 
• leukopenia 
• dizziness
• nausea
• diarrhea

Serious side effects of Zoliflodacin include:

• hypersensitivity reactions, including rash and pruritus
• testicular toxicity and potential impairment of male fertility
• Clostridioides difficile (C.difficile) infection (CDI)-associated diarrhea

Rare side effects of Zoliflodacin include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult & Pediatric dosage

Granules for oral suspension

• 3g/unit-dose packet 

Gonorrhea

Adult and pediatric dosage

• Weight 35 kg to less than 50 kg: 3 g orally as a single dose; take on empty stomach, 1 hour before or 2 hour after food
• Weight of 50 kg and more: 3 g orally as a single dose; take with food

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

Drug Interaction Overview

• CYP3A4 substrate
  • Moderate and strong CYP3A4 inducers
  • Contraindicated
  • Moderate and strong CYP3A4 inducers are predicted to result in decreased plasma zoliflodacin concentrations and may reduce efficacy

Contraindications

• Known history of hypersensitivity
• Coadministration with moderate or strong CYP3A4 inducers

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Zoliflodacin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Zoliflodacin?”

Cautions

• Embryofetal toxicity
  • Potential risk for pregnant females
  • Based on data from animal studies, may cause fetal harm when administered to a pregnant female at clinically relevant doses
  • Reproductive and developmental toxicity studies at AUC exposures 1.6-fold (mice) and 8.5-fold (rats) the maximum recommended human dose (MRHD) of zoliflodacin administered to pregnant rodents during organogenesis resulted in fetal malformations (exencephaly) and increased embryo-fetal loss
  • Advise pregnant females about potential fetal risk with maternal exposure
• Avoid use during pregnancy
  • Obtain a pregnancy test before initiation of treatment in females of reproductive potential
  • Potential risk related to males with female partners of reproductive potential
  • Based on data from an animal toxicity study, risk of early pregnancy loss may be increased in female partners of males treated with zoliflodacin
  • A reduced number of live embryos and increased number of embryonic losses were observed in untreated female rats mated with male rats administered zoliflodacin at exposures ~3.9x clinical exposure at the MRHD for 4 weeks
  • Advise males with female partners of reproductive potential to use effective contraception for at least 3 months after administration dose
• Testicular toxicity and risks to male fertility
  • Based on findings from animal studies, may cause testicular toxicity and impair male fertility
  • In repeat-dose toxicity studies, rats and dogs administered zoliflodacin for durations of 2 days to 4 weeks at AUC exposures 3- to 11-times the MRHD experienced minimal to moderate decreased spermatogenesis and testicular histopathological changes
  • In rats, loss of male rat fertility was no longer observed 4 weeks after the last dose; however, testicular histopathological changes in rats and dogs were only partially reversible after 2 to 3 months
  • An evaluation of spermatogenesis has not been conducted in humans
  • Advise males that zoliflodacin may cause testicular toxicity and impair male fertility
• Hypersensitivity reactions
  • Hypersensitivity reactions, including rash and pruritus, reported
  • Contraindicated in patients with a known history of hypersensitivity
  • Before therapy is instituted, carefully inquire about previous hypersensitivity reactions
  • If allergic reaction occurs, institute appropriate supportive measures
• Clostridioides difficile Infection
  • CDI has been reported with use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis
  • Treatment with antibacterial agents alters normal flora of colon leading to overgrowth of C difficile
  • C difficile produces toxins A and B, which contributes to development of CDI
  • Hypertoxin producing strains of C difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy
  • CDI must be considered in all patients who present with diarrhea following antibacterial drug use
  • Careful medical history is necessary since CDI has been reported to occur over 2 months after administration of antibacterial agents
  • If CDI is suspected or confirmed, ongoing antibacterial drug use not directed against C difficile may need to be discontinued
  • Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C difficile, and surgical evaluation should be instituted as clinically indicated
• Development of Drug-Resistant Bacteria
  • Prescribing zoliflodacin in absence of a proven or strongly suspected bacterial infection or prophylactic indication is unlikely to provide benefit to patient and increases risk of the development of drug-resistant bacteria

Pregnancy and Lactation

Pregnancy

• Based on findings from animal studies, zoliflodacin may cause fetal malformations or increased embryo-fetal loss when administered to a pregnant female. 
• There are no human data on zoliflodacin use in pregnancy to evaluate the drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. 
• Advise pregnant females about the potential risk to the fetus with maternal exposure to zoliflodacin

Lactation

• There are no data on the presence of zoliflodacin in either human or animal milk, effects on the breastfed infant, or effects on milk production. 
• If zoliflodacin is present in breast milk, intestinal flora alteration in the breastfed infant could occur. 
• The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for zoliflodacin and any potential adverse effects on the breastfed infant from zoliflodacin or from the underlying maternal condition.