Gepotidacin

Gepotidacin is a prescription medication indicated for the treatment of: 

• uncomplicated urinary tract infections (uUTI) caused by susceptible microorganisms (i.e., Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii complex, Staphylococcus saprophyticus, and Enterococcus faecalis) in female adult and pediatric patients aged 12 years and older weighing at least 40 kg
• uncomplicated urogenital gonorrhea caused by susceptible strains of Neisseria gonorrhoeae in adult and pediatric patients aged 12 years and older weighing at least 45 kg who have limited or no alternative treatment options.

Gepotidacin is available under the following different brand names: Blujepa.

Common side effects of Gepotidacin include:

• diarrhea 
• soft stools
• nausea
• abdominal pain
• dizziness
• vomiting
• gas (flatulence)
• yeast infections (vulvovaginal candidiasis)
• headache
• fatigue
• hyperhidrosis

Serious side effects of Gepotidacin include:

• QTc prolongation symptoms include fast, pounding, or uneven heartbeat, feeling lightheaded, feeling dizzy, passing out and fainting
• increased cholinergic effects causing diarrhea, vomiting, fainting, trouble saying words clearly, muscle spasms, nausea, excess saliva in the mouth, sweating profusely, stomach pain, irregular heartbeat (heart block), fainting, slow heartbeat (bradycardia), chest tightness causing difficulty breathing, and seizures
• allergic reactions include hives, fainting or dizziness, rash, and swelling of the lips, tongue, or throat
• severe Clostridioides difficile infection (CDI), causing stomach cramps, diarrhea that does not go away, fever, watery diarrhea, and bloody stools
• dysarthria

Rare side effects of Gepotidacin 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; and sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious 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 and pediatric dosage

Tablet

• 750 mg

Urinary tract infections

Adult dosage

• 1500 mg orally two times a day for 5 days

Uncomplicated Urogenital Gonorrhea

Adult and pediatric dosage

• 3,000 mg orally x 2 doses taken approximately 12 hours apart

Pediatric dosage

• 1500 mg orally two times a day with food for 5 days

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, healthcare provider, or pharmacist first.

Drug interaction overview

• Substrate and weak inhibitor of CYP3A4
• CYP3A4 inhibitors
  • Strong inhibitors: Avoid
  • Moderate inhibitors: Avoid if using to treat uncomplicated urogenital gonorrhea
  • Increases exposure of gepotidacin
• CYP3A4 inducers
  • Strong inducers: Avoid
  • Moderate inducers: Avoid if used to treat uncomplicated urogenital gonorrhea
  • Decreases in exposure of gepotidacin
• CYP3A4 sensitive substrates
  • Avoid
    • Avoid coadministration with drugs that are extensively metabolized by CYP3A4 and have a narrow therapeutic index (eg, quinidine, cyclosporine)
• Digoxin
  • Monitor
    • Due to increased digoxin systemic exposure, consider monitoring digoxin serum concentrations, as appropriate, if coadministered
• Cholinergic drugs
  • Monitor for exaggerated neuromuscular blockage or excessive cholinergic effects
  • Gepotidacin is an acetylcholinesterase inhibitor; there is potential for an exaggerated effect of coadministered succinylcholine-type neuromuscular blocking agents, resulting in a delay in recovery of neuromuscular function
  • Gepotidacin may augment the effects of other acetylcholinesterase inhibitors (eg, donepezil)
• Anticholinergic drugs
  • Monitor anticholinergic drugs for decreased efficacy
  • Potential for antagonistic effect with systemic anticholinergic medications (eg, benztropine, oxybutynin) or nondepolarizing neuromuscular blocking agents
• Drugs that prolong the QTc interval
  • Avoid
    • Additive effects may occur
    • If coadministration is unavoidable, monitor and correct serum electrolyte abnormalities and obtain an ECG before administration and during treatment, as clinically indicated

Contraindications

• History of severe hypersensitivity to gepotidacin

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

QTc prolongation

• Dose and concentration-dependent prolongation of QTc interval observed
• Avoid gepotidacin in patients with a history of QTc interval prolongation or those with relevant pre-existing cardiac disease, patients taking antiarrhythmic agents, or other medications that may potentially prolong QTc interval
• Owing to increased systemic exposure of gepotidacin and risk of QTc interval prolongation, avoid in patients with:
  • Concomitant use of strong CYP3A4 inhibitors
  • Severe renal impairment (eGFR below 30 mL/min)
  • Severe hepatic impairment (Child-Pugh Class C)
• Avoid in patients with uncomplicated urogenital gonorrhea with the following risk factors for increased gepotidacin exposure
  • Concomitant use of moderate CYP3A4 inhibitors
  • 2 or more of the following risk factors: Body weight 45-60 kg, moderate renal impairment (eGFR 30-59 mL/min), and/or moderate hepatic impairment (Child-Pugh Class B)
• If coadministration is unavoidable, monitor and correct serum electrolyte abnormalities and obtain ECG before administration and during treatment, as clinically indicated

Acetylcholinesterase inhibition

• Gepotidacin is a reversible acetylcholinesterase inhibitor
• Increased cholinergic effects can be associated with severe adverse reactions, including atrioventricular block, bradycardia, bronchospasm, seizures/convulsions, and vasovagal syncope
• Monitor patients with medical conditions that may be exacerbated by acetylcholinesterase inhibition

Hypersensitivity reactions

• Hypersensitivity reactions reported
• Contraindicated in patients with a history of severe hypersensitivity to gepotidacin; inquire about previous hypersensitivity before initiating
• If an allergic reaction occurs, discontinue and institute appropriate supportive measures

Clostridioides difficile infection

• Antibacterial agents alter the normal flora of the colon, leading to overgrowth of C difficile
• C difficile produces toxins A and B, which contribute to the development of C difficile-associated diarrhea (CDAD); Hypertoxin-producing isolates of C difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy
• CDAD is reported with the use of nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis
• Consider CDAD in all patients who present with diarrhea following antibacterial therapy
• Carefully review the patient’s medical history since CDAD has been reported to occur over 2 months after administration
• If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C difficile may need to be discontinued
• Institute appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C difficile, and surgical evaluation as clinically indicated

Development of drug-resistant bacteria

• Prescribing antibiotics in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit and increases the risk of developing drug-resistant bacteria

Pregnancy and Lactation

• Data is unavailable on use during pregnancy to evaluate for a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes

Pregnancy exposure registry

• Pregnant women exposed to gepotidacin and healthcare providers are encouraged to contact GlaxoSmithKline at 1-888-825-5249

Lactation

• There is no data on the presence of the drug in human milk, its effects on breastfed children, or milk production