gepotidacin

Acts as a triazaacenaphthylene antibacterial that inhibits type II topoisomerases including bacterial topoisomerase II (DNA gyrase) and topoisomerase IV, which then inhibits DNA replication. Also acts as a reversible acetylcholinesterase inhibitor.

Therapeutic effects:

Death of susceptible bacteria with resolution of infection.

Spectrum:

Active against Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Staphylococcus saprophyticus, and Enterococcus faecalis.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A isoenzyme. 52% excreted in feces (30% as unchanged drug); 31% excreted in urine (20% as unchanged drug).

Half-Life: 9 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Severe hypersensitivity;
QT interval prolongation or pre-existing cardiac disease;
Severe renal impairment or end-stage renal disease;
Severe hepatic impairment.

Use Cautiously in:

OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children <12 yr and <40 kg (safety and effectiveness not established;
Geri: Consider age-related impairment of renal function in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: QT interval prolongation

GI: diarrhea, abdominal pain, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), flatulence, nausea, vomiting

GU: vulvovaginal candidiasis

Neuro: dizziness, headache

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHLYAXIS)

Interactions ⬆ ⬇

Drug-drug:

Antiarrhythmics and QT interval prolonging medications may ↑ risk of QT interval prolongation; avoid concurrent use.
Strong CYP3A4 inhibitors, including itraconazole or ketoconazole, may ↑ levels and risk of QT interval prolongation; avoid concurrent use.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of CYP3A4 substrates, including cyclosporine, midazolam, or quinidine; avoid concurrent use.
May ↑ levels and risk of toxicity of digoxin; closely monitor digoxin levels.
May exaggerate the neuromuscular effects of succinylcholine.
May ↑ risk of cholinergic adverse effects of other acetylcholinesterase inhibitors, including donepezil.
May antagonize the effects of anticholinergic drugs, including benztropine or oxybutynin and non-depolarizing neuromuscular blockers.

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥12 yr and ≥40 kg): 1,500 mg twice daily for 5 days.

Availability ⬆ ⬇

Film-coated tablets: 750 mg

Assessment ⬆ ⬇

Assess for signs/symptoms of resolving infection (worsening urinary tract infection include fever, dysuria, polyuria, hematuria, flank pain, suprapubic pain or pressure) during therapy.
Assess cardiac history baseline; avoid use in patients with long QT syndrome or cardiac arrhythmias associated with prolonged QT interval. If administration cannot be avoided in these patients, correct serum electrolyte abnormalities and collect an ECG prior to administration, during treatment, and as clinically indicated.
Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Have epinephrine, antihistamine, and resuscitative equipment close by. If hypersensitivity reaction occurs,immediately discontinue gepotidacin and treat as clinically indicated.
Monitor for signs/symptoms of excess acetylcholinesterase inhibition including dysarthria, presyncope, muscle spasms, diarrhea, nausea, vomiting, abdominal pain, hypersalivation, and hyperhidrosis, especially if administered with drugs with additive cholinergic effects.
Monitor for signs/symptoms of CDAD including watery diarrhea with mucus, fever, abdominal pain or cramping, anorexia, nausea, and in severe cases, dehydration, and blood or pus in the stool. May occur >2 mo after therapy. Report promptly to health care provider.

Lab Test Considerations:

Obtain specimen for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Monitor serum electrolytes including potassium, calcium, and magnesium in patients with QT interval prolongation.

Implementation ⬆ ⬇

PO: Administer after a meal to ↓ GI intolerance.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of gepotidacin. Instruct patient to take medication as directed after a meal. If a dose is missed, take it as soon as possible; do not double the dose to make up for the missed dose. Keep out of children's reach. Do not share medication with others, even if they have similar symptoms; may be harmful. Advise patient to read Patient Information before starting therapy.
Warn patient to report symptoms of arrhythmias and QT interval prolongation (fast heart beat, skipped beats, palpitations, dizziness, lightheaded, trouble breathing, faintness).
Advise the patient to report signs and symptoms of excessive cholinergic symptoms such as dizziness, trouble breathing, sweating a lot, feeling very weak, stomach cramps, nausea, vomiting, diarrhea, or drooling.
Advise patients and family to call 911 and seek urgent treatment for signs and symptoms of hypersensitivity reactions such as difficulty breathing, chest tightness, hives, rash, feeling lightheaded, itching, swelling of the face, lips, tongue or throat.
Instruct patient to notify health care professional immediately if diarrhea, abdominal cramping, fever, or bloody stools occur and not to treat with antidiarrheals without consulting health care professionals.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Encourage pregnant patient to enroll in registry that monitors outcomes in women exposed to gepotidacin during pregnancy by calling 1-888-825-5249.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇