Antibiotic, Quinolone

Treatment of the following infections when caused by susceptible bacteria: Acute bacterial exacerbation of chronic bronchitis due to S. pneumoniae, H. influenzae, H. parainfluenzae, M. catarrhalis, or S. aureus; acute sinusitis due to S. pneumoniae, H. influenzae; community acquired pneumonia due to S. pneumoniae, H. influenzae, H. parainfluenzae, M. catarrhalis, S. aureus, M. pneumoniae, C. pneumoniae, or L. pneumophilia; uncomplicated urinary tract infections (cystitis) due to E. coli, K. pneumoniae, or P. mirabilis; complicated urinary tract infections due to E. coli, K. pneumoniae, or P. mirabilis; pyelonephritis due to E. coli; uncomplicated urethral and cervical gonorrhea; acute, uncomplicated rectal infections in women due to N. gonorrhoeae

C

No adequate or well-controlled studies in pregnant women. Should be used during pregnancy only when the potential benefit justifies the potential risk to the fetus.

Hypersensitivity to gatifloxacin, other quinolone antibiotics, or any component

Use with caution in patients with significant bradycardia or acute myocardial ischemia. May have potential to prolong Q-T interval; should avoid in patients with uncorrected hypokalemia, or concurrent administration of other medications known to prolong the Q-T interval (including class Ia and class III antiarrhythmics, cisapride, erythromycin, antipsychotics, and tricyclic antidepressants). Safety and effectiveness in pediatric patients (<18 years of age) have not been established. Experience in immature animals has resulted in permanent arthropathy. Use with caution in individuals at risk of seizures (CNS disorders or concurrent therapy with medications which may lower seizure threshold). Discontinue in patients who experience significant CNS adverse effects (dizziness, hallucinations, suicidal ideation or actions). Use caution in renal dysfunction (dosage adjustment required) and in severe hepatic insufficiency (no data available). Use caution in patients with diabetes - glucose regulation may be altered.

3% to 10%:

Central nervous system: Headache (3%), dizziness (3%)

Gastrointestinal: Nausea (8%), diarrhea (4%)

Genitourinary: Vaginitis (6%)

Local: Injection site reactions (5%)

0.1% to 3%: Allergic reaction, chills, fever, back pain, chest pain, palpitation, abdominal pain, constipation, dyspepsia, glossitis, oral candidiasis, stomatitis, mouth ulceration, vomiting, peripheral edema, abnormal dreams, insomnia, paresthesia, tremor, vasodilation, vertigo, dyspnea, pharyngitis, rash, sweating, abnormal vision, taste perversion, tinnitus, dysuria, hematuria, elevated serum transaminases, elevated alkaline phosphatase, increased serum bilirubin, increased serum amylase

<0.1% (Limited to important or life-threatening symptoms): Abnormal thinking, agitation, alcohol intolerance, anorexia, anxiety, arthralgia, arthritis, asthenia, ataxia, bone pain, bradycardia, breast pain, bronchospasm, cheilitis, colitis, confusion, cyanosis, depersonalization, depression, diabetes mellitus, dry skin, dysphagia, ear pain, ecchymosis, edema, epistaxis, euphoria, eye pain, facial edema, flatulence, gastritis, gastrointestinal hemorrhage, gingivitis, halitosis, hallucination, hematemesis, hostility, hyperesthesia, hyperglycemia, hypertension, hypertonia, hyperventilation, hypoglycemia, leg cramps, lymphadenopathy, maculopapular rash, metrorrhagia, migraine, myalgia, myasthenia, neck pain, nervousness, panic attacks, paranoia, parosmia, pruritus, pseudomembranous colitis, psychosis, ptosis, rectal hemorrhage, seizures, somnolence, stress, tachycardia, taste disturbance, thirst, tongue edema, vesiculobullous rash

Potential symptoms of overdose may include CNS excitation, seizures, QT prolongation, and arrhythmias (including torsade de pointes). Patients should be monitored by continuous EKG in the event of an overdose. Management is supportive and symptomatic. Not removed by dialysis.

Gatifloxacin may prolong Q-T interval; avoid use with drugs which prolong Q-T interval (including class Ia and class III antiarrhythmics, erythromycin, cisapride, antipsychotics, and cyclic antidepressants).

Metal cations (magnesium, aluminum, iron, and zinc) bind quinolones in the gastrointestinal tract and inhibit absorption (by up to 98%). Antacids, electrolyte supplements, sucralfate, quinapril, and some didanosine formulations should be avoided. Gatifloxacin should be administered 4 hours before or 8 hours after these agents.

Antineoplastic agents may decrease the absorption of quinolones

Calcium carbonate was not found to alter the absorption of gatifloxacin.

Cimetidine, and other H₂ antagonists may inhibit renal elimination of quinolones

Digoxin levels may be increased in some patients by gatifloxacin; monitor for increased effect/concentrations.

Foscarnet has been associated with an increased risk of seizures with some quinolones

H₂ antagonists and proton pump inhibitors may decrease absorption of some quinolones

Loop diuretics: Serum levels of some quinolones are increased by loop diuretic administration. May diminish renal excretion.

NSAIDs: The CNS stimulating effect of some quinolones may be enhanced, resulting in neuroexcitation and/or seizures. This effect has not been observed with gatifloxacin.

Probenecid: Blocks renal secretion of gatifloxacin, increasing AUC and half-life.

Warfarin: The hypoprothrombinemic effect of warfarin is enhanced by some quinolone antibiotics. No significant effect has been demonstrated for gatifloxacin, however, monitoring of the INR during concurrent therapy is recommended by the manufacturer.

Store at 25°C (77°F). Do not freeze injection. Injection must be diluted to a concentration of 2 mg/mL prior to administration. Compatible with 5% dextrose in water, 0.9% sodium chloride, lactated Ringer's and 5% dextrose injection, 5% sodium bicarbonate injection, water for injection, PlasmaLyte® 56/5% dextrose injection. Compatible with 5% dextrose or 0.45% sodium chloride containing up to 20 mEq/L potassium chloride.

Gatifloxacin is a DNA gyrase inhibitor, and also inhibits topoisomerase IV. DNA gyrase (topoisomerase II) is an essential bacterial enzyme that maintains the superhelical structure of DNA. DNA gyrase is required for DNA replication and transcription, DNA repair, recombination, and transposition; inhibition is bactericidal.

Absorption: Well absorbed after oral administration

Distribution: V_d: 1.5-2.0 L/kg; concentrates in alveolar macrophages and lung parenchyma

Protein binding: 20%

Metabolism: Only 1% metabolized. No interaction with hepatic microsomal enzymes.

Bioavailability: 96%

Half-life: 7.1-13.9 hours (up to 30-40 hours in ESRD or CAPD)

Time to peak: Oral: 1 hour

Elimination: In urine, as unchanged drug (5% in feces)

Adult: Oral, I.V.:

Acute sinusitis: 400 mg every 24 hours for 10 days

Community acquired pneumonia: 400 mg every 24 hours for 7-14 days

Uncomplicated urinary tract infections (cystitis): 200-400 mg every 24 hours for 3 days

Complicated urinary tract infections: 400 mg every 24 hours for 7-10 days

Acute pyelonephritis: 400 mg every 24 hours for 7-10 days

Uncomplicated urethral gonorrhea in men, cervical or rectal gonorrhea in women: 400 mg single dose

Dosage adjustment in renal impairment: Creatinine clearance <40 mL/minute (or patients on hemodialysis/CAPD) should receive an initial dose of 400 mg, followed by a subsequent dose of 200 mg every 24 hours. Patients receiving single-dose or 3-day therapy for appropriate indications do not require dosage adjustment.

Dosage adjustment in hepatic impairment: No dosage adjustment is required in mild-moderate hepatic disease. No data are available in severe hepatic impairment (Child-Pugh Class C).

Elderly: No dosage adjustment is required based on age, however, assessment of renal function is particularly important in this population.

Concentrated injection (10 mg/mL) must be diluted to 2 mg/mL prior to administration. No further dilution is required for premixed 100 mL and 200 mL solutions.

WBC, signs of infection

No information available to require special precautions

No effects or complications reported

May be taken with or without food. Drink plenty of fluids. Avoid exposure to direct sunlight during therapy and for several days following. Do not take antacids within 4 hours before or 2 hours after dosing. Contact your physician immediately if signs of allergy occur or if signs of tendon inflammation or pain occur. Do not discontinue therapy until your course has been completed. Take a missed dose as soon as possible, unless it is almost time for your next dose.

Infusion: 2 mg/mL (100 mL, 200 mL)

Injection: 10 mg/mL (20 mL, 40 mL)

Tablet: 200 mg, 400 mg

Blondeau JM, "Expanded Activity and Utility of the New Fluoroquinolones: A Review," Clinical Therapeutics, 1999, 21(1):3-40.

"Gatifloxacin and Moxifloxacin: Two New Fluoroquinolones," The Medical Letter, 2000, Vol 42, 1072:15.

Perry CM, Barman Balfour JA, Lamb HM, "Gatifloxacin," Drugs, 1999, 58(4):683-96.