Prescription Drugs

CLINICAL PHARMACOLOGY Gatifloxacin is administered as a racemate, with the disposition and antibacterial activity of the R- and S-enantiomers virtually identical. Absorption Gatifloxacin is well absorbed from the gastrointestinal tract after oral administration and can be given without regard to food. The absolute bioavailability of gatifloxacin is 96%. Peak plasma concentrations of gatifloxacin usually occur 1-2 hours after oral dosing. The oral and intravenous routes of administration for TEQUIN can be considered interchangeable, since the pharmacokinetics of gatifloxacin after 1-hour intravenous administration are similar to those observed for orally administered gatifloxacin when equal doses are administered (Figure 1) (see DOSAGE AND ADMINISTRATION). Figure 1: Mean Plasma Concentration-Time Profiles of Gatifloxacin Following Intravenous (IV) and Oral (PO) Administration of a Single 400-mg Dose to Healthy Subjects. Pharmacokinetics The mean (SD) pharmacokinetic parameters of gatifloxacin following oral administration to healthy subjects with bacterial infections and subjects with renal insufficiency are listed in Table 1. The mean (SD) pharmacokinetic parameters of gatifloxacin following intravenous administration to healthy subjects are listed in Table 2. Table 1: Gatifloxacin Pharmacokinetic Parameters- Oral Administration Cmax (mg/mL) Tmaxa (h) AUCb (mg.h/mL) T ½ (h) Cl/F (mL/min) C1R (mL/min) UR (%) 200 mg - Healthy Volunteers Single dose (n=12) 2.0 ±0.4 1.00 (0.50, 2.50) 14.2 ± 0.4 - 241 ±40 - 73.8 ± 10.9 400 mg - Healthy Volunteers Single dose (n=202)c 3.8 ±1.0 1.00 (0.50, 6.00) 33.0 ± 6.2 7.8±1.3 210 ±44 151 ±46 72.4 ± 18.1 Multiple dose (n=18) 4.2 ±1.3 1.50 (0.50, 4.00) 34.4 ± 5.7 7.1±0.6 199 ±31 159 ±34 80.2 ±12.1 400 mg - Patients with Infection Multiple dose (n=140)d 4.2 ±1.9 - 51.3±20.4 - 147 ±48 - - 400 mg - Single Dose Subjects with Renal Insufficiency Clcr50 - 89 mL/min (n=8) 4.4 ±1.1 1.13 (0.75-2.00) 48.0 ± 12.7 11.2±2.8 148 ±41 124 ± 38 83.7±7.8 Clcr 30 - 49 mL/min (n=8) 5.1 ±1.8 0.75 (0.50, 6.00) 74.9 ± 12.6 17.2±8.5 92 ±17 67 ±24 71.1 ±17.4 Clcr 0.5 Resistant (R) c These interpretive standards are applicable to agar dilution tests with GC agar base and 1% defined growth supplement. A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable. A report of "Intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentration usually achievable; other therapy should be selected. Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard gatifloxacin powder should provide the following MIC values: Microorganism MIC Range (µg/mL) Enterococcus faecalis ATCC 29212 0.12 - 1.0 Escherichia coli ATCC 25922 0.008 - 0.03 Haemophilus influenzae ATCC 49247d 0.004 - 0.03 Neisseria gonorrhoeae ATCC 49226e 0.002 - 0.016 Pseudomonas aeruginosa ATCC 27853 0.5 - 2.0 Staphylococcus aureus ATCC 29213 0.03 - 0.12 Streptococcus pneumoniae ATCC 49619f 0.12 - 0.5 d This quality control range is applicable to only H. influenzae ATCC 49247 tested by a broth microdilution procedure using HTM. 1 e This quality control range is applicable to only N. gonorrhoeae ATCC 49226 tested by an agar dilution procedure using GC agar base with 1% defined growth supplement. 1 f This quality control range is applicable to only S. pneumoniae ATCC 49619 tested by a microdilution procedure using cation-adjusted Mueller-Hinton broth with 2-5% lysed horse blood. 1 Diffusion techniques: Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 5 µg gatifloxacin to test the susceptibility of microorganisms to gatifloxacin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5-µg gatifloxacin disk should be interpreted according to the following criteria: The following zone diameter interpretive criteria should be used for testing Enterobacteriaceae and Staphylococcus species: Zone Diameter (mm) Interpretation ³18 Susceptible (S) 15 - 17 Intermediate (I) £14 Resistant (R) For testing Haemophilus influenzae and Hemophilus parainfluenzaeg: Zone Diameter (mm) Interpretation ³18 Susceptible (S) g This zone diameter standard is applicable only to tests with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium (HTM).2 The current absence of data on resistant strains precludes defining any results other than "Susceptible". Strains yielding MIC results suggestive of a "nonsusceptible" category should be submitted to a reference laboratory for further testing. For testing Streptococcus pneumoniaeh: Zone Diameter (mm) Interpretation ³21 Susceptible (S) 18 - 20 Intermediate (I) £17 Resistant (R) For testing Streptococcus species other than Streptococcus pneumoniaeh: Zone Diameter (mm) Interpretation ³18 Susceptible (S) 15 - 17 Intermediate (I) £14 Resistant (R) h These zone diameter standards only apply to tests performed using Mueller-Hinton agar supplemented with 5% sheep blood incubated in 5% CO2.2 For testing Neisseria gonorrhoeae i: Zone Diameter (mm) Interpretation ³38 Susceptible (S) 34 - 37 Intermediate (I) £33 Resistant (R) i These interpretive standards are applicable to disk diffusion tests with GC agar base and 1% defined growth supplement incubated in 5% CO2. Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for gatifloxacin.2 As with standardized dilution techniques, methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 5-µg gatifloxacin disk should provide the following zone diameters in these laboratory quality control strains: Microorganism Zone Diameter Range (mm) Escherichia coli ATCC 25922 30-37 Haemophilus influenzae ATCC 49247j 33-41 Neisseria gonorrhoeae ATCC 49226k 45-56 Pseudomonas aeruginosa ATCC 27853 20-28 Staphylococcus aureus ATCC 25923 27-33 Streptococcus pneumoniae ATCC 49619l 24-31 j This quality control range applies to tests conducted with Haemophilus influenzae ATCC 49247 using Haemophilus Test Medium (HTM)2. k This quality control range is only applicable to tests conducted with N. gonorrhoeae ATCC 49226 performed by disk diffusion using GC agar base and 1% defined growth supplement2. l This quality control range is applicable only to tests conducted with S. pneumoniae ATCC 49619 performed by disk diffusion using Mueller-Hinton agar supplemented with 5% defibrinated sheep blood. CLINICAL STUDIES Community-Acquired Bacterial Pneumonia and Community-Acquired Pneumonia Due to Multi-Drug Resistant Streptococcus pneumoniae (MDRSP)* Clinical efficacy of gatifloxacin in the treatment of community-acquired bacterial pneumonia (CAP) was evaluated in two non-comparative Phase II/III studies and three Phase III studies comparing oral TEQUIN (gatifloxacin (removed from us market - may 2006)) to oral clarithromycin, TEQUIN (gatifloxacin (removed from us market - may 2006)) IV/oral to levofloxacin IV/oral, and TEQUIN (gatifloxacin (removed from us market - may 2006)) IV/oral to ceftriaxone IV (+/- erythromycin IV) with step-down to oral clarithromycin. Success rates for clinically evaluable patients with a bacterial pathogen isolated at baseline (see INDICATIONS AND USAGE) ranged from 88% to 90% for TEQUIN (gatifloxacin (removed from us market - may 2006)) -treated patients. Success rates were not statistically different from comparator therapy. Gatifloxacin was also effective for the treatment of community-acquired pneumonia caused by multi-drug resistant Streptococcus pneumoniae (MDRSP) isolates. Of 27 clinically and microbiologically evaluable patients with MDRSP isolates obtained primarily from post-marketing studies of patients with CAP, 100% achieved clinical and bacteriological success post-therapy. The clinical cure rates and bacteriological success rates are shown in the table below. *Multidrug-resistant Streptococcus pneumoniae (MDRSP) includes isolates previously known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC 2 µg/mL), 2nd generation cephalosporins (eg, cefuroxime), macrolides, tetracyclines, and trimethoprim/ sulfamethoxazole. Table 6: Clinical and Bacteriological Success Rates for Gatifloxacin- Treated MDRSP CAP Patients (Population: Valid for Efficacy) Screening Susceptibility Clinical Success n/Na Bacteriological Success n/Nb Penicillin-resistant 10/10 (100%) 10/10 (100%) 2nd generation cephalosporin-resistant* 13/13 (100%) 13/13 (100%) Macrolide-resistant** 24/24 (100%) 24/24 (100%) Trimethoprim/sulfamethoxazole-resistant 12/12 (100%) 12/12 (100%) Tetracylcine-resistant 14/14 (100%) 14/14 (100%) a n = number of patients successfully treated; N = number of clinically evaluable patients with MDRSP (froma total of 27 patients). b n = number of patients successfully treated (presumed eradication or eradication); N = number of microbiologically evaluable patients with MDRSP (from a total of 27 patients). * 2nd generation cephalosporin tested was cefuroxime. ** Clarithromycin and erythromycin were the macrolide antimicrobials tested. Not all isolates were resistant to all antimicrobial classes tested. Success and eradication rates are summarized in the table below. Table 7: Clinical Success and Bacteriological Eradication Rates for Gatifloxacin-Treated MDRSP CAP Patients (Population: Valid for Efficacy) Streptococcus pneumoniae with MDRSP Clinical Success Rate Bacteriological Eradication Rate Resistant to at least 2 antimicrobials 12/12 (100%) 12/12 (100%) Resistant to at least 3 antimicrobials 12/12 (100%) 12/12 (100%) Resistant to at least 4 antimicrobials 2/2 (100%) 2/2 (100%) Resistant to at least 5 antimicrobials 1/1 (100%) 1/1 (100%) Bacteremias with MDRSP 3/3 (100%) 3/3 (100%) REFERENCES 1. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grows Aerobically - Fifth Edition; Approved Standard, NCCLS Document M7-A5, Vol. 20, No. 2, NCCLS, Wayne, PA, January 2000. 2. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests - Seventh Edition; Approved Standard, NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne, PA, January 2000.

Find Lowest Prices on TEQUIN® (gatifloxacin) Tablets (gatifloxacin) Injection (gatifloxacin in 5% dextrose) Injection DESCRIPTION TEQUIN® is available as TEQUIN (gatifloxacin) Tablets for oral administration and TEQUIN (gatifloxacin) Injection and TEQUIN (gatifloxacin in 5% dextrose) Injection for intravenous administration. To reduce the development of drug-resistant bacteria and maintain the effectiveness of TEQUIN (gatifloxacin removed from us market - may 2006) and other antibacterial drugs, TEQUIN (gatifloxacin removed from us market - may 2006) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. TEQUIN contains gatifloxacin, a synthetic broad-spectrum 8-methoxyfluoroquinolone antibacterial agent for oral or intravenous administration. Chemically, gatifloxacin is (±)-1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid sesquihydrate. The chemical structure is: Its empirical formula is C19H22FN3O4·1.5 H2O and its molecular weight is 402.42. Gatifloxacin is a sesquihydrate crystalline powder and is white to pale yellow in color. It exists as a racemate, with no net optical rotation. The solubility of the compound is pH dependent. The maximum aqueous solubility (40-60 mg/mL) occurs at a pH range of 2 to 5. TEQUIN (gatifloxacin removed from us market - may 2006) Tablets TEQUIN (gatifloxacin removed from us market - may 2006) Tablets are available as 200-mg and 400-mg white, film-coated tablets and contain the following inactive ingredients: hypromellose, magnesium stearate, methylcellulose, microcrystalline cellulose, polyethylene glycol, polysorbate 80, simethicone, sodium starch glycolate, sorbic acid, and titanium dioxide. TEQUIN (gatifloxacin removed from us market - may 2006) Injection for Intravenous Administration TEQUIN (gatifloxacin removed from us market - may 2006) Injection is available in 40-mL (400-mg) single-use vials as a sterile, preservative-free aqueous solution of gatifloxacin with pH ranging from 3.5 to 5.5. TEQUIN (gatifloxacin in 5% dextrose) Injection is also available in ready-to-use 100-mL (200-mg) and 200-mL (400-mg) flexible bags as a sterile, preservative-free aqueous solution of gatifloxacin with pH ranging from 3.5 to 5.5. The appearance of the intravenous solution may range from light yellow to greenish-yellow in color. The color does not affect nor is it indicative of product stability. The intravenous formulation contains dextrose, anhydrous, USP or dextrose, monohydrate, USP and Water for Injection, USP, and may contain hydrochloric acid and/or sodium hydroxide for pH adjustment.

TEQUIN® (gatifloxacin) Tablets (gatifloxacin) Injection (gatifloxacin in 5% dextrose) Injection DESCRIPTION TEQUIN® is available as TEQUIN (gatifloxacin) Tablets for oral administration and TEQUIN (gatifloxacin) Injection and TEQUIN (gatifloxacin in 5% dextrose) Injection for intravenous administration. To reduce the development of drug-resistant bacteria and maintain the effectiveness of TEQUIN (gatifloxacin removed from us market - may 2006) and other antibacterial drugs, TEQUIN (gatifloxacin removed from us market - may 2006) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. TEQUIN contains gatifloxacin, a synthetic broad-spectrum 8-methoxyfluoroquinolone antibacterial agent for oral or intravenous administration. Chemically, gatifloxacin is (±)-1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid sesquihydrate. The chemical structure is: Its empirical formula is C19H22FN3O4·1.5 H2O and its molecular weight is 402.42. Gatifloxacin is a sesquihydrate crystalline powder and is white to pale yellow in color. It exists as a racemate, with no net optical rotation. The solubility of the compound is pH dependent. The maximum aqueous solubility (40-60 mg/mL) occurs at a pH range of 2 to 5. TEQUIN (gatifloxacin removed from us market - may 2006) Tablets TEQUIN (gatifloxacin removed from us market - may 2006) Tablets are available as 200-mg and 400-mg white, film-coated tablets and contain the following inactive ingredients: hypromellose, magnesium stearate, methylcellulose, microcrystalline cellulose, polyethylene glycol, polysorbate 80, simethicone, sodium starch glycolate, sorbic acid, and titanium dioxide. TEQUIN (gatifloxacin removed from us market - may 2006) Injection for Intravenous Administration TEQUIN (gatifloxacin removed from us market - may 2006) Injection is available in 40-mL (400-mg) single-use vials as a sterile, preservative-free aqueous solution of gatifloxacin with pH ranging from 3.5 to 5.5. TEQUIN (gatifloxacin in 5% dextrose) Injection is also available in ready-to-use 100-mL (200-mg) and 200-mL (400-mg) flexible bags as a sterile, preservative-free aqueous solution of gatifloxacin with pH ranging from 3.5 to 5.5. The appearance of the intravenous solution may range from light yellow to greenish-yellow in color. The color does not affect nor is it indicative of product stability. The intravenous formulation contains dextrose, anhydrous, USP or dextrose, monohydrate, USP and Water for Injection, USP, and may contain hydrochloric acid and/or sodium hydroxide for pH adjustment.

INDICATIONSTEQUIN (gatifloxacin) is indicated for the treatment of infections due to susceptible strains of the designated microorganisms in the conditions listed below (see DOSAGE AND ADMINISTRATION). Acute bacterial exacerbation of chronic bronchitis due to Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, or Staphylococcus aureus. Acute sinusitis due to Streptococcus pneumoniae or Haemophilus influenzae. Community-acquired pneumonia due to Streptococcus pneumoniae (including multidrug-resistant strains [MDRSP])*, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila. (See Clinical Studies.) Uncomplicated skin and skin structure infections (ie, simple abscesses, furuncles, folliculitis, wound infections, and cellulitis) due to Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes. NOTE: An insufficient number of patients with the diagnosis of impetiginous lesions were available for evaluation. Uncomplicated urinary tract infections (cystitis) due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. Complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. Pyelonephritis due to Escherichia coli. Uncomplicated urethral and cervical gonorrhea due to Neisseria gonorrhoeae. Acute, uncomplicated rectal infections in women due to Neisseria gonorrhoeae (see WARNINGS). To reduce the development of drug-resistant bacteria and maintain the effectiveness of TEQUIN (gatifloxacin (removed from us market - may 2006)) and other antibacterial drugs, TEQUIN (gatifloxacin (removed from us market - may 2006)) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. *Multidrug-resistant Streptococcus pneumoniae (MDRSP) includes isolates previously known as PRSP (penicillin-resistant Streptococcus pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC 2 µg/mL), 2nd generation cephalosporins (eg, cefuroxime), macrolides, tetracyclines, and trimethoprim/ sulfamethoxazole. DOSAGE AND ADMINISTRATIONThe recommended dosage for TEQUIN (gatifloxacin (removed from us market - may 2006)) Tablets or TEQUIN (gatifloxacin (removed from us market - may 2006)) Injection is described in Table 4. Doses of TEQUIN (gatifloxacin (removed from us market - may 2006)) are administered once every 24 hours. These recommendations apply to all patients with a creatinine clearance ³40 mL/min. For patients with a creatinine clearance

OVERDOSEGatifloxacin exhibits a low potential for acute toxicity in animal studies. The minimum lethal oral doses in rats and dogs were greater than 2000 mg/kg and 1000 mg/kg, respectively. The minimum lethal intravenous dose was 144 mg/kg in rats and greater than 45 mg/kg in dogs. Clinical signs observed included decreased activity and respiratory rate, vomiting, tremors, and convulsions. In the event of acute oral overdose, the stomach should be emptied by inducing vomiting or by gastric lavage. The patient should be carefully observed (including ECG monitoring) and given symptomatic and supportive treatment. Adequate hydration should be maintained. Gatifloxacin is not efficiently removed from the body by hemodialysis (approximately 14% recovered over 4 hours) or by chronic ambulatory peritoneal dialysis (CAPD) (approximately 11% recovered over 8 days). CONTRAINDICATIONSTEQUIN is contraindicated in persons with a history of hypersensitivity to gatifloxacin or any member of the quinolone class of antimicrobial agents.

SIDE EFFECTSOver 5000 patients have been treated with gatifloxacin in single- and multiple-dose clinical efficacy trials worldwide. In gatifloxacin studies, the majority of adverse reactions were described as mild in nature. Gatifloxacin was discontinued for adverse events thought related to drug in 2.7% of patients. Drug-related adverse events classified as possibly, probably, or definitely related with a frequency of ³3% in patients receiving gatifloxacin in single- and multiple-dose clinical trials are as follows: nausea 8%, vaginitis 6%, diarrhea 4%, headache 3%, dizziness 3%. In patients who were treated with either intravenous gatifloxacin or with intravenous followed by oral therapy, the incidence of adverse events was similar to those who received oral therapy alone. Local injection site reactions (redness at injection site) were noted in 5% of patients. Additional drug-related adverse events (possibly, probably, or definitely related) considered clinically relevant that occurred in ³0.1% to

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Topical Ophthalmic Use Only Gatifloxacin ophthalmic solution should not be introduced directly into the anterior chamber of the eye. Growth of Resistant Organisms with Prolonged Use As with other anti-infectives, prolonged use of gatifloxacin ophthalmic solution, 0.5% may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, discontinue use and institute alternative therapy. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and where appropriate, fluoroscein staining. Avoidance of Contact Lens Wear Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis or during the course of therapy with gatifloxacin ophthalmic solution (see PATIENT INFORMATION). Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility There was no increase in neoplasms among B6C3F1 mice given gatifloxacin in the diet for 18 months at doses averaging 81 mg/kg/day in males and 90 mg/kg/day in females. These doses are approximately 1600-fold and 1800-fold higher, respectively, than the maximum recommended ophthalmic dose of 0.05 mg/kg/day in a 50 kg human. There was no increase in neoplasms among Fischer 344 rats given gatifloxacin in the diet for 2 years at doses averaging 47 mg/kg/day in males and 139 mg/kg/day in females (900- and 2800-fold higher, respectively, than the maximum recommended ophthalmic dose). A statistically significant increase in the incidence of large granular lymphocyte (LGL) leukemia was seen in males treated with a high dose of approximately 2000-fold higher than the maximum recommended ophthalmic dose. Fischer 344 rats have a high spontaneous background rate of LGL leukemia and the incidence in high-dose males only slightly exceeded the historical control range established for this strain. In genetic toxicity tests, gatifloxacin was positive in 1 of 5 strains used in bacterial reverse mutation assays: Salmonella strain TA102. Gatifloxacin was positive in in vitro mammalian cell mutation and chromosome aberration assays. Gatifloxacin was positive in in vitro unscheduled DNA synthesis in rat hepatocytes but not human leukocytes. Gatifloxacin was negative in in vivo micronucleus tests in mice, cytogenetics test in rats, and DNA repair test in rats. The findings may be due to the inhibitory effects of high concentrations on eukaryotic type II DNA topoisomerase. There were no adverse effects on fertility or reproduction in rats given gatifloxacin orally at doses up to 200 mg/kg/day (approximately 4000-fold higher than the maximum recommended ophthalmic dose for gatifloxacin). Use In Specific Populations Pregnancy Pregnancy Category C Teratogenic Effects: There were no teratogenic effects observed in rats or rabbits following oral gatifloxacin doses up to 50 mg/kg/day (approximately 1000-fold higher than the maximum recommended ophthalmic dose). However, skeletal/craniofacial malformations or delayed ossification, atrial enlargement, and reduced fetal weight were observed in fetuses from rats given ?150 mg/kg/day (approximately 3000-fold higher than the maximum recommended ophthalmic dose). In a perinatal/postnatal study, increased late postimplantation loss and neonatal/perinatal mortalities were observed at 200 mg/kg/day (approximately 4000-fold higher than the maximum recommended ophthalmic dose). Because there are no adequate and well-controlled studies in pregnant women, gatifloxacin ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers Gatifloxacin is excreted in the breast milk of rats. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when gatifloxacin is administered to a nursing woman. Pediatric Use The safety and effectiveness of gatifloxacin in infants below one year of age have not been established. Gatifloxacin has been demonstrated in clinical trials to be safe and effective for the treatment of bacterial conjunctivitis in pediatric patients one year or older (see Clinical Studies). Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients.