Professional Information

Gatifloxacin

Pronouncation: (ga-ti-FLOKS-a-sin)
Class: Antibiotic, Fluoroquinolone, Ophthalmic

Trade Names:
Tequin
- Tablets 200 mg
- Tablets 400 mg
- Solution for injection (single-use vials) 400ߙmg
- Solution for injection (premix) 200ߙmg
- Solution for injection (premix) 400ߙmg

Trade Names:
Zymar
- Ophthalmic solution 3 mg/mL

Pharmacology

Treatment of infections caused by susceptible strains of the designated microorganism.

Pharmacokinetics

Absorption

Bioavailability is about 96%. C _max is about 2 to 4.2 mcg/mL (dose-proportional). T _max is about 1 h (about 1.5 h after multiple doses). AUC is about 14.2ߙmcg•h/mL after a 200 mg dose and about 33ߙmcg•h/mL after a 400 mg dose.

Distribution

Protein binding is about 20%. Mean Vd _ss 1.5 to 2 L/kg.

Metabolism

Limited.

Elimination

Mean t _½ ranges from 7 to 14 h. Renal Cl ranges from 124 to 161 mL/min. Less than 1% excreted in urine as ethylenediamine and methylethylenediamine metabolites. Primarily renally excreted as unchanged drug via glomerular filtration and tubular secretion. May also undergo minimal biliary and/or intestinal elimination.

Special Populations

Renal Function Impairment
Moderate renal function impairment (CrCl 30 to 49ߙmL/min)

57% decrease in total Cl. AUC decreased by 2 times.

Severe renal function impairment (CrCl less than 30ߙmL/min)

77% decrease in total Cl. AUC increased by 4 times.

Dosage reduction recommended with a CrCl less than 40ߙmL/min.

Hepatic Function Impairment

In patients with moderate (Child-Pugh B) hepatic function impairment, C _max increased 32% and AUC _0-∞ increased 23%. No dosage adjustment is necessary.

Indications and Usage

For treatment of bacterial infections, including chronic bronchitis; acute sinusitis; community-acquired pneumonia; uncomplicated and complicated UTIs; pyelonephritis; uncomplicated urethral and cervical gonorrhea; uncomplicated skin and skin structure infections; uncomplicated rectal infections in women; bacterial conjunctivitis (ophthalmic).

Unlabeled Uses

Atypical pneumonia; chronic prostatitis.

Contraindications

Standard considerations.

Dosage and Administration

Acute Bacterial Exacerbation of Chronic Bronchitis

PO/IV 400 mg every 24 h for 5 days.

Acute Pyelonephritis

PO/IV 400 mg every 24 h for 7 to 10 days.

Acute Sinusitis

PO/IV 400 mg every 24 h for 10 days.

Bacterial Conjunctivitis

Ophthalmic Days 1 and 2, instill 1 drop in affected eye(s) every 2 h while awake, up to 8 times/day. Days 3 through 7, instill 1 drop up to 4 times daily while awake.

Complicated UTIs

PO/IV 400 mg every 24 h for 7 to 10 days.

Community-Acquired Pneumonia

PO/IV 400 mg every 24 h for 7 to 14 days.

Uncomplicated Skin and Skin Structure Infections

PO/IV 400 mg every 24 h for 7 to 10 days.

Hemodialysis; Continuous Peritoneal Dialysis

PO/IV 400 mg initial dose then subsequent dose of 200 mg PO/IV every 24 h (on day 2 of dosing).

Renal Function Impairment
Adults CrCl more than 40 mL/min

PO/IV 400ߙmg initial dose then subsequent dose of 400 mg. PO/IV every 24 h (on day 2 of dosing).

CrCl less than 40 mL/min

PO/IV 400 mg initial dose then subsequent dose of 200 mg. PO/IV every 24 h (on day 2 of dosing).

Uncomplicated Urethral Gonorrhea in Men; Endocervical and Rectal Gonorrhea in Women

PO/IV 400ߙmg every 24 h in a single dose.

Uncomplicated UTIs (Cystitis)

PO/IV 400 or 200 mg every 24 h. Single dose for 3 days.

General Advice

Administer by IV infusion over a period of 60ߙmin. Avoid rapid or bolus IV infusion.
Single-use vials require dilution prior to administration.
When switching from IV to oral administration, no dosage adjustment is necessary. Patients whose therapy is started with the injection may be switched to tablets when clinically indicated.

Oral

Administer oral gatifloxacin more than 4ߙh before the administration of ferrous sulfate, dietary supplements containing zinc, magnesium, or iron (eg, multivitamins); aluminum/magnesium-containing antacids, didanosine-buffered tablets, buffered solution, buffered powder, or oral suspension.
Administer without regard to food, including milk and dietary supplements containing calcium.

Ophthalmic solution

For topical instillation into eye(s) only.
Have patient tilt head back, pull lower lid out to make pocket, and instill medication into conjunctival sac. Have patient close eyes and apply light finger pressure to bridge of nose for 1 to 2 min. Advise patient not to blink or rub eyes.
If using other topical ophthalmic drugs, separate each medication by at least 5 min.

Storage/Stability

Store at room temperature (59° to 86°F); do not freeze pre-mix bags.

Oral

Store tablets at room temperature (59° to 86°F).

Ophthalmic

Store at controlled room temperature (59° to 77°F). Protect from freezing. Keep container tightly closed.

Drug Interactions

Aluminum- and magnesium-containing antacids, didanosine-buffered tablets, iron, or zinc salts

May decrease the bioavailability of gatifloxacin.

Antiarrhythmic agents (ie, class IA [eg, procainamide, quinidine], class III [eg, amiodarone, sotalol]), antipsychotics, cisapride, erythromycin, tricyclic antidepressants, any other drug known to prolong the QTc interval

May increase the risk of life-threatening cardiac arrhythmias, including torsades de pointes.

Digoxin

Plasma level of digoxin may be elevated, increasing the risk of toxicity.

NSAIDs

Coadministration may increase the risks of CNS stimulation and convulsions.

Probenecid

Renal Cl of gatifloxacin may be decreased, prolonging the t _½ and increasing plasma levels of gatifloxacin.

Incompatibility

Amphotericin B; amphotericin B cholesteryl sulfate; cefoperazone sodium; cefonicid; cefozitin sodium; diazepam; furosemide; heparin sodium; mezlocillin disodium; phenytoin sodium; piperacillin sodium/tazobactam sodium; potassium phosphates; vancomycin in dextrose 5% injection.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitations; hypertension.

CNS

Abnormal dream; insomnia; paresthesia; tremors; vasodilation; vertigo; agitation; anxiety; confusion; headache; dizziness; asthenia.

Dermatologic

Rash; sweating; pruritus; dry skin.

EENT

Abnormal vision; tinnitus.

Ophthalmic

Conjunctival irritation; increased lacrimation; keratitis; papillary conjunctivitis; chemosis; conjunctival hemorrhage; dry eye; eye discharge; eye irritation; eye pain; eyelid edema.

GI

Abdominal pain; constipation; dyspepsia; glossitis; oral moniliasis; stomatitis; mouth ulcer; vomiting; nausea; diarrhea; anorexia.

Genitourinary

Dysuria; hematuria.

Metabolic

Peripheral and face edema; hyperglycemia.

Respiratory

Dyspnea; pharyngitis.

Miscellaneous

Allergic reaction; chills; fever; back pain; chest pain; taste perversion.

Precautions

Monitor

Ocular adverse reactions

Monitor patient for signs and symptoms of ocular adverse reactions (eg, burning, stinging pain, irritation) and improvement in conjunctivitis. Notify health care provider if conjunctivitis is not improving or is worsening or if intolerable adverse reactions occur.

Pregnancy

Category C .

Lactation

Not known if excreted in human milk.

Children

PO/IV

Safety and efficacy not established in patients younger than 18 yr of age.

Ophthalmic

Safety and efficacy not established in patients younger than 1 yr of age.

Hypersensitivity

Mild to life-threatening. Discontinue drug at first sign of hypersensitivity reaction.

Special Risk Patients

Renal function impairment.

Superinfection

Use of antibiotics may result in bacterial or fungal overgrowth. Monitor for symptoms of superinfections (eg, vaginitis, stomatitis, diarrhea).

Convulsions/Toxic psychosis

CNS stimulation, lowering of the seizure threshold, and psychotic reactions have been reported with similar agents. Use with caution in patients with seizures or CNS disorders.

Pseudomembranous colitis

Consider possibility in patients with diarrhea.

QT effects

Gatifloxacin may prolong the QT interval and should be avoided in patients with a history of prolongation of the QTc interval, uncorrected electrolyte disorder (eg, hypokalemia, hypomagnesemia), and in patients receiving drugs that prolong the QTc interval.

Tendonitis

Inflammation and rupture of tendons have been associated with use of fluoroquinolone antibiotics.

Overdosage

Symptoms

Possible QTc prolongation.

Patient Information

Instruct patient that gatifloxacin should be taken 4 h before any aluminum or magnesium based antacids, ferrous sulfate, and multivitamins.
Instruct patient to stop treatment and inform health care provider if experiencing pain, inflammation, or rupture of tendon, and to rest or refrain from exercise until diagnosis of tendonitis or tendon rupture has been excluded.
Instruct patient that drug may be taken with or without food and to drink fluids liberally.
Instruct patient regarding the signs and symptoms of hypersensitivity; discontinue the medication at once and seek treatment immediately if occurring.
Instruct patient to inform health care provider of any personal or family history of QTc prolongation or proarrhythmic conditions such as recent hypokalemia, significant bradycardia, acute myocardial ischemia, or history of convulsions.
Instruct patient to inform health care provider of any prescription or OTC medications concurrently being taken.
Inform patient of the additive effects of other drugs such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants to further QTc prolongation.
Instruct patient to contact primary caregiver if experiencing palpitations or fainting spells.
Inform patient that drug may cause dizziness and lightheadedness and not to drive an automobile, operate dangerous machinery, or engage in activities that require mental alertness and coordination.
Instruct patient to complete full course of therapy, even if symptoms of infection have resolved.

Ophthalmic solution
Remind patients not to wear contact lenses if signs and symptoms of bacterial conjunctivitis occur.
Review dosing regimen with patient.
Teach patient proper technique for instilling eye drops: wash hands; do not allow dropper to touch eye. Tilt head back and look up; pull lower eyelid down; instill prescribed number of drops. Close eye for 1 to 2 min and apply gentle pressure to bridge of nose. Do not rub eye.
Advise patient that if more than 1 topical ophthalmic drug is being used to administer the drugs at least 5 min apart.
Advise patient to inform health care provider if ocular adverse reactions occur and become bothersome or if infection is not improving.