Gatilox IV

Dextrose:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• Directions for use of pharmacy bulk package container
• How supplied
• Gatilox IV (Dextrose) reviews

INDICATIONS AND USAGE

70% Gatilox IV (Dextrose) Injection USP is indicated as a caloric component in a parenteral nutrition regimen. 70% Gatilox IV (Dextrose) Injection USP is used with an appropriate protein (nitrogen) source in the prevention of nitrogen loss or in the treatment of negative nitrogen balance in patients where: (1) the alimentary tract cannot or should not be used, (2) gastrointestinal absorption of protein is impaired, or (3) metabolic requirements for protein are substantially increased, as with extensive burns.

CONTRAINDICATIONS

The infusion of 70% Gatilox IV (Dextrose) Injection USP is contraindicated in patients having intracranial or intraspinal hemorrhage, in patients who are severely dehydrated, in patients who are anuric, and in patients in hepatic coma.

Solutions containing Gatilox IV (Dextrose) may be contraindicated in patients with hypersensitivity to corn products.

WARNINGS

This injection is for compounding only, not for direct infusion.

Dilute before use to a concentration which will, when administered with an amino acid (nitrogen) source, result in an appropriate calorie to gram of nitrogen ratio and which has an osmolarity consistent with the route of administration.

Unless appropriately diluted, the infusion of hypertonic Gatilox IV (Dextrose) injection into a peripheral vein may result in vein irritation, vein damage, and thrombosis. Strongly hypertonic nutrient solutions should only be administered through an indwelling intravenous catheter with the tip located in a large central vein such as the superior vena cava.

Use of 70% Gatilox IV (Dextrose) Injection USP to prepare parenteral nutritional admixtures may be incompatible with other components, especially calcium and phosphate salts and lipid emulsions. Incompatibility of admixed components can produce precipitates which may cause particulate emboli. Use 70% Gatilox IV (Dextrose) Injection USP only to prepare formulations that are known to be stable: refer to standard texts for further information.

The administration of intravenous solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the electrolyte concentration.

WARNING: 70% Gatilox IV (Dextrose) Injection USP contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 µg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Prolonged infusion of isotonic or hypotonic Gatilox IV (Dextrose) in water may increase the volume of extracellular fluid and cause water intoxication.

Solutions containing Gatilox IV (Dextrose) without electrolytes should not be administered simultaneously with blood through the same infusion set because of the possibility of agglomeration.

Excessive administration of potassium-free Gatilox IV (Dextrose) solutions may result in significant hypokalemia. Serum potassium levels should be maintained and potassium supplemented as required.

In very low birth weight infants, excessive or rapid administration of Gatilox IV (Dextrose) injection may result in increased serum osmolality and possible intracerebral hemorrhage.

PRECAUTIONS

General

This solution should be used with care in patients with hypervolemia, renal insufficiency, urinary tract obstruction, or impending or frank cardiac decompensation.

Solutions containing Gatilox IV should be used with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.

Essential electrolytes, minerals, and vitamins should be supplied as needed.

Hypokalemia may develop during parenteral administration of hypertonic Gatilox IV (Dextrose) solutions. Sufficient amounts of potassium should be added to Gatilox IV (Dextrose) solutions administered to fasting patients with good renal function, especially those on digitalis therapy.

To minimize the risk of possible incompatibilities arising from mixing this solution with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration. See WARNINGS .

Do not use plastic container in series connection.

If administration of 70% Gatilox IV (Dextrose) Injection USP after admixture or dilution is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result. If administration is not controlled by a pumping device, refrain from applying excessive pressure (>300mmHg) causing distortion to the container such as wringing or twisting. Such handling could result in breakage of the container.

This solution is intended for intravenous administration after admixture or dilution using sterile equipment. When using an automated compounding device replace all disposable components as recommended by manufacturer and at least every 24 hours.

Aseptic technique is essential with the use of sterile preparations for compounding nutritional admixtures. Discard container within 4 hours of entering closure.

Administration of hypertonic Gatilox IV (Dextrose) and amino acid solutions via central venous catheter may be associated with complications which can be prevented or minimized by careful attention to all aspects of the procedure. This includes attention to solution preparation, administration and patient monitoring.

It is essential that a carefully prepared protocol, based upon current medical practice, be followed, preferably by an experienced team. The package insert of the protein (nitrogen) source should be consulted for dosage and all precautionary information.

Use only if solution is clear and container and seals are intact.

70% Gatilox IV (Dextrose) Injection USP contains no more than 25 µg/L of aluminum.

Laboratory Tests

Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Significant deviations from normal concentrations may require tailoring of the electrolyte pattern, in these or alternative solutions.

Drug Interactions

Caution must be exercised in the administration of 70% Gatilox IV Injection USP to patients receiving corticosteroids or corticotropin. Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store. Dispose of any unused product. See WARNINGS .

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Gatilox IV (Dextrose) Injections USP have not been performed to evaluate carcinogenic potential, mutagenic potential or effects on fertility.

Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies with Gatilox IV Injections, USP in pregnant women and animal reproduction studies have not been conducted with this drug. Therefore, it is not known whether Gatilox IV (Dextrose) Injections USP can cause fetal harm when administered to a pregnant woman. Gatilox IV (Dextrose) Injections USP should be given during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

Intrapartum maternal intravenous infusion of glucose-containing solutions may produce maternal hyperglycemia with subsequent fetal hyperglycemia and fetal metabolic acidosis. Fetal hyperglycemia can result in increased fetal insulin levels which may result in neonatal hypoglycemia following delivery. Consider the potential risks and benefits for each specific patient before administering Gatilox IV (Dextrose) Injection, USP.

Nursing Mothers

It is not known if this drug is present in human milk. Because many drugs are present in human milk, caution should be exercised when Gatilox IV Injections USP are administered to a nursing woman.

Pediatric Use

The use of Gatilox IV (Dextrose) in pediatric patients is based on clinical practice (see DOSAGE AND ADMINISTRATION ). Because of their hypertonicity, 70% Gatilox IV (Dextrose) Injections must be diluted prior to administration.

Newborns – especially those born premature and with low birth weight - are at increased risk of developing hypo- or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long term adverse effects. Hypoglycemia in the newborn can cause prolonged seizures, coma and brain damage. Hyperglycemia has been associated with intraventricular hemorrhage, late onset bacterial and fungal infection, retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, prolonged length of hospital stay, and death.

Geriatric Use

An evaluation of literature revealed no clinical experience identifying differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

See WARNINGS .

ADVERSE REACTIONS

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia. Incompatibility of admixed components can produce precipitates which may cause particulate emboli.

Hyperosmolar syndrome, resulting from excessively rapid administration of concentrated Gatilox IV (Dextrose) may cause hypovolemia, dehydration, mental confusion and/or loss of consciousness. Too rapid infusion of hypertonic solutions may cause local pain and venous irritation. Rate of administration should be adjusted according to tolerance. Use of the largest peripheral vein and a small bore needle is recommended. (See DOSAGE AND ADMINISTRATION .)

Hypersensitivity reactions, including anaphylaxis and chills.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.

OVERDOSAGE

In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient’s condition and institute appropriate corrective treatment.

DOSAGE AND ADMINISTRATION

This solution is for intravenous use only after admixture or dilution.

70% Gatilox IV Injection USP is designed for use with automated compounding devices for preparing intravenous nutritional admixtures or for the filling of empty sterile syringes. Dosages will be in accordance with the recommendation of the prescribing physician. 70% Gatilox IV (Dextrose) Injection USP is not intended for direct infusion. Admixtures should be made by, or under the direction of, a pharmacist using strict aseptic technique under a laminar flow hood. Compounded admixtures may be stored under refrigeration for up to 24 hours. Administration of admixtures should be completed within 24 hours after removal from refrigeration.

Dosage is to be directed by a physician and is dependent upon age, weight, clinical condition of the patient and laboratory determinations. Frequent laboratory determinations and clinical evaluation are essential to monitor changes in blood glucose and electrolyte concentrations, and fluid and electrolyte balance during prolonged parenteral therapy.

Fluid administration should be based on calculated maintenance or replacement fluid requirements for each patient.

Pediatric Use

The dosage selection and constant infusion rate of intravenous Gatilox IV (Dextrose) must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/hypoglycemia. Frequent monitoring of serum glucose concentrations is required when Gatilox IV (Dextrose) is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume depends on the age, weight, clinical and metabolic conditions of the patient, concomitant therapy and should be determined by the consulting physician experienced in pediatric intravenous fluid therapy.

Directions for Use of Pharmacy Bulk Package Container

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration or admixture and final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration, whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible.

70% Gatilox IV (Dextrose) Injection USP in the Pharmacy Bulk Package is intended for use in the preparation of sterile, intravenous admixtures.

Refer to standard texts and guidelines on the preparation of parenteral nutritional admixtures.

When compounding admixtures, use aseptic technique. Mix thoroughly.

Do not store any unused portion of 70% Gatilox IV (Dextrose) Injection USP.

TO OPEN:

• Inspect overwrap. Do not use if overwrap has been damaged.
• Do not use unless solution is clear and closure is intact.
• Tear overwrap starting from the tear notches. (Figure 1)
  

• Inspect the container for minute leaks by squeezing inner bag firmly. If leaks are found, discard the bag as sterility may be impaired.
• For compounding only. Do not use for direct infusion
  

  PREPARATION FOR ADMIXING
  

  Note: Important Admixing Information
  

  
  

• The Pharmacy Bulk Package is to be used only in a suitable work area such as a laminar air flow hood (or an equivalent clean air compounding area).
• The contents are restricted to the preparation of admixtures for infusion or, through a sterile transfer device, for the filling of empty sterile syringes.
• Additives may be incompatible with the fluid withdrawn from this container. When compounding admixtures, use aseptic technique, mix thoroughly and do not store.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution container permits. (see PRECAUTIONS, General )

• Do not use/penetrate blocked port.
  

• Remove aluminum foil of set port at the bottom of container.
• Attach suitable transfer device or compounding set (Figure 2). Refer to complete directions accompanying device.
• Hang bag on suitable fixture (Figure 3).
• Once container closure has been penetrated, withdrawal of content should be completed within 4 hours.

HOW SUPPLIED

70% Gatilox IV (Dextrose) Injection USP is supplied in 2000 mL Pharmacy Bulk Package containers packaged 4 per case.

NDC REF SIZE

0264-7387-50 S8705 2000 mL

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product.

Rx only

Initiated: February 2015

B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

www.bbraun.com

Y36-002-865 LD-355-2

Gatifloxacin:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• % carton
• Gatilox IV (Gatifloxacin) reviews

1 INDICATIONS AND USAGE

Gatilox IV (Gatifloxacin) ophthalmic solution 0.5% is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:

Aerobic Gram-Positive Bacteria:

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus mitis group^*

Streptococcus oralis ^*

Streptococcus pneumoniae

Aerobic Gram-Negative Bacteria:

Haemophilus influenzae

^*Efficacy for this organism was studied in fewer than 10 infections.

Gatilox IV (Gatifloxacin) ophthalmic solution is a topical fluoroquinolone anti-infective indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:

Haemophilus influenzae, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mitis group^* , Streptococcus oralis ^* , Streptococcus pneumoniae

^*Efficacy for this organism was studied in fewer than 10 infections. (1)

2 DOSAGE AND ADMINISTRATION

Patients 1 year of age or older: Instill one drop every two hours in the affected eye(s) while awake, up to 8 times on Day 1. Instill one drop two to four times daily in the affected eye(s) while awake on Days 2 through 7.

Patients 1 year of age or older: Instill one drop every two hours in the affected eye(s) while awake, up to 8 times on Day 1. Instill one drop two to four times daily in the affected eye(s) while awake on Days 2 through 7. (2)

3 DOSAGE FORMS AND STRENGTHS

Four (4) mL bottle containing 2.5 mL of a 0.5% sterile topical ophthalmic solution.

4 mL size bottle filled with 2.5 mL of Gatilox IV (Gatifloxacin) ophthalmic solution, 0.5%. (3)

4 CONTRAINDICATIONS

None

None

5 WARNINGS AND PRECAUTIONS

• Topical Ophthalmic Use Only
• Growth of Resistant Organisms with Prolonged Use (5.2)
• Avoidance of Contact Lenses. Patients should not wear contact lenses if they have signs or symptoms of bacterial conjunctivitis or during the course of therapy with Gatilox IV (Gatifloxacin) ophthalmic solution (5.3)

5.1 Topical Ophthalmic Use Only

Gatilox IV (Gatifloxacin) ophthalmic solution should not be introduced directly into the anterior chamber of the eye.

5.2 Growth of Resistant Organisms with Prolonged Use

As with other anti-infectives, prolonged use of Gatilox IV 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.

5.3 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 Gatilox IV (Gatifloxacin) ophthalmic solution [see PATIENT COUNSELING INFORMATION (17.2)].

6 ADVERSE REACTIONS

Most common adverse reactions occurring in ≥ 1 % of patients included worsening of conjunctivitis, eye irritation, dysgeusia, and eye pain.

To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

In clinical studies with Gatilox IV (Gatifloxacin), the most frequently reported adverse reactions occurring in ≥ 1% of patients in the Gatilox IV (Gatifloxacin) study population (N=717) were: worsening of the conjunctivitis, eye irritation, dysgeusia, and eye pain.

Additional adverse events reported with other formulations of Gatilox IV (Gatifloxacin) ophthalmic solution include chemosis, conjunctival hemorrhage, dry eye, eye discharge, eyelid edema, headache, increased lacrimation, keratitis, papillary conjunctivitis, and reduced visual acuity.

7 DRUG INTERACTIONS

Specific drug interaction studies have not been conducted with Gatilox IV (Gatifloxacin) ophthalmic solution.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

Teratogenic Effects: There were no teratogenic effects observed in rats or rabbits following oral Gatilox IV 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 post-implantation 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, Gatilox IV (Gatifloxacin) ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

Gatilox IV (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 Gatilox IV (Gatifloxacin) ophthalmic solution is administered to a nursing woman.

8.4 Pediatric Use

The safety and effectiveness of Gatilox IV ophthalmic solution in infants below one year of age have not been established. Gatilox IV (Gatifloxacin) ophthalmic solution 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 (14)].

8.5 Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

11 DESCRIPTION

Gatilox IV (Gatifloxacin) sterile ophthalmic solution is an 8-methoxyfluoroquinolone anti-infective for the treatment of bacterial conjunctivitis. Its chemical name is (±)-1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid, sesquihydrate. Its molecular formula is C₁₉H₂₂FN₃O₄ · 1½H₂O, and its molecular weight is 402.42. Its chemical structure is:

Gatilox IV (Gatifloxacin) ophthalmic solution is a clear, pale yellow to greenish yellow, sterile, preserved aqueous solution with an osmolality of 270 to 310 mOsm/kg and a pH of 5.3-5.6.

Gatilox IV (Gatifloxacin) ophthalmic solution contains Active: Gatilox IV (Gatifloxacin), anhydrous 0.5% (5 mg/mL); Inactives: benzalkonium chloride 0.005%; edetate disodium dihydrate; purified water; and sodium chloride. May contain hydrochloric acid and/or sodium hydroxide to adjust pH.

Structure formula

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Gatilox IV is a fluoroquinolone antibacterial [see CLINICAL PHARMACOLOGY (12.4)].

12.3 Pharmacokinetics

Gatilox IV (Gatifloxacin) ophthalmic solution 0.3% or 0.5% was administered to one eye of 6 healthy male subjects each in an escalated dosing regimen starting with a single 2 drop dose, then 2 drops 4 times daily for 7 days, and finally 2 drops 8 times daily for 3 days. At all time points, serum Gatilox IV (Gatifloxacin) levels were below the lower limit of quantification (5 ng/mL) in all subjects.

12.4 Microbiology

Gatilox IV (Gatifloxacin) is an 8-methoxyfluoroquinolone with a 3-methylpiperazinyl substituent at C7. The antibacterial action of Gatilox IV (Gatifloxacin) results from inhibition of DNA gyrase and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription, and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The mechanism of action of fluoroquinolones including Gatilox IV (Gatifloxacin) is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, Gatilox IV (Gatifloxacin) may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to Gatilox IV (Gatifloxacin). There is no cross-resistance between Gatilox IV (Gatifloxacin) and the aforementioned classes of antibiotics. Cross resistance has been observed between systemic Gatilox IV (Gatifloxacin) and some other fluoroquinolones.

Resistance to Gatilox IV (Gatifloxacin) in vitro develops via multiple-step mutations. Resistance to Gatilox IV (Gatifloxacin) in vitro occurs at a general frequency of 1 x 10^-7 to 10^-10.

Gatilox IV (Gatifloxacin) has been shown to be active against most isolates of the following organisms both microbiologically and clinically, in conjunctival infections as described in the INDICATIONS AND USAGE, Section 1 .

Aerobic Gram-Positive Bacteria:

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus mitis group^*

Streptococcus oralis ^*

Streptococcus pneumoniae

Aerobic Gram-Negative Bacteria:

Haemophilus influenzae

^*Efficacy for this organism was studied in fewer than 10 infections.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no increase in neoplasms among B6C3F1 mice given Gatilox IV (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 Gatilox IV (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, Gatilox IV (Gatifloxacin) was positive in 1 of 5 strains used in bacterial reverse mutation assays: Salmonella strain TA102. Gatilox IV (Gatifloxacin) was positive in in vitro mammalian cell mutation and chromosome aberration assays. Gatilox IV (Gatifloxacin) was positive in in vitro unscheduled DNA synthesis in rat hepatocytes but not human leukocytes. Gatilox IV (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 Gatilox IV (Gatifloxacin) orally at doses up to 200 mg/kg/day (approximately 4000-fold higher than the maximum recommended ophthalmic dose for Gatilox IV (Gatifloxacin) ophthalmic solution).

14 CLINICAL STUDIES

In two randomized, double-masked, multicenter clinical trials, where patients 1-89 years of age were dosed for 5 days, Gatilox IV (Gatifloxacin) ophthalmic solution was clinically superior to its vehicle on day 6 in patients with conjunctivitis and positive conjunctival cultures. Clinical outcomes for the trials demonstrated clinical success (resolution of conjunctival hyperaemia and conjunctival discharge) of 58% (193/333) for the gatifloxacin-treated groups versus 45% (148/325) for the vehicle-treated groups. Microbiological outcomes for the same clinical trials demonstrated a statistically superior eradication rate for causative pathogens of 90% (301/333) for Gatilox IV (Gatifloxacin) versus 70% (228/325) for vehicle. Please note that microbiological eradication does not always correlate with clinical outcome in anti-infective trials.

16 HOW SUPPLIED/STORAGE AND HANDLING

Gatilox IV (Gatifloxacin) ophthalmic solution 0.5% is supplied sterile in LDPE DROP-TAINERs white bottles with natural LDPE dispensing plugs and tan polypropylene (PP) closure in the following size:

2.5 mL in 4 mL bottle: NDC 61314-672-25

Storage: Store at 20° to 25°C (68° to 77°F).

Protect from freezing.

17 PATIENT COUNSELING INFORMATION

17.1 Avoiding Contamination of the Product

Patients should be instructed to avoid contaminating the applicator tip with material from the eye, fingers, or other source.

17.2 Avoidance of Contact Lens Wear

Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.

Manufactured by Alcon Laboratories, Inc.

Fort Worth, Texas 76134 for

Sandoz Inc.

Princeton, NJ 08540

Rev. 04/2016

0.5 % Carton

NDC 61314-672-25

Gatilox IV (Gatifloxacin)

Ophthalmic

Solution

0.5%

For Use in the Eyes Only

2.5 mL

SANDOZ

2.5-mL