Gatifloxacin: Difference between revisions

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<!--FDA-Labeled Indications and Dosage (Adult)-->
<!--FDA-Labeled Indications and Dosage (Adult)-->
|fdaLIADAdult======Condition1=====
|fdaLIADAdult======Bacterial conjunctivitis=====


* Dosing Information
* Dosing Information


:* Dosage
:*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.
 
=====Condition2=====
 
* Dosing Information
 
:* Dosage
 
=====Condition3=====
 
* Dosing Information
 
:* Dosage
 
=====Condition4=====
 
* Dosing Information
 
:* Dosage


<!--Off-Label Use and Dosage (Adult)-->
<!--Off-Label Use and Dosage (Adult)-->


<!--Guideline-Supported Use (Adult)-->
<!--Guideline-Supported Use (Adult)-->
|offLabelAdultGuideSupport======Condition1=====
|fdaLIADPed======Bacterial conjunctivitis=====
 
* Developed by:
 
* Class of Recommendation:
 
* Strength of Evidence:
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport======Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====


* Dosing Information
* Dosing Information


:* Dosage
:*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.  
 
=====Condition2=====
 
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.


<!--Off-Label Use and Dosage (Pediatric)-->
<!--Off-Label Use and Dosage (Pediatric)-->


<!--Guideline-Supported Use (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Contraindications-->
|contraindications=None
|contraindications=None
|warnings=5.1 Topical Ophthalmic Use Only
|warnings='''Topical Ophthalmic Use Only'''


ZYMAXID® solution should not be introduced directly into the anterior chamber of the eye.
* ZYMAXID® solution should not be introduced directly into the anterior chamber of the eye.


5.2 Growth of Resistant Organisms with Prolonged Use
'''Growth of Resistant Organisms with Prolonged Use'''


As with other anti-infectives, prolonged use of ZYMAXID® (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, fluorescein staining.
* As with other anti-infectives, prolonged use of ZYMAXID® (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, fluorescein staining.


5.3 Avoidance of Contact Lens Wear
'''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 ZYMAXID® (see PATIENT COUNSELING INFORMATION, 17.2).
* 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 ZYMAXID®.
|clinicalTrials=6.1 Clinical Studies Experience
|clinicalTrials='''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.
*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 ZYMAXID®, the most frequently reported adverse reactions occurring in ≥ 1% of patients in the gatifloxacin study population (N=717) were: worsening of the conjunctivitis, eye irritation, dysgeusia, and eye pain.
*In clinical studies with ZYMAXID®, the most frequently reported adverse reactions occurring in ≥ 1% of patients in the gatifloxacin study population (N=717) were: worsening of the conjunctivitis, eye irritation, dysgeusia, and eye pain.


Additional adverse events reported with other formulations of gatifloxacin ophthalmic solution include chemosis, conjunctival hemorrhage, dry eye, eye discharge, eyelid edema, headache, increased lacrimation, keratitis, papillary conjunctivitis, and reduced visual acuity.
*Additional adverse events reported with other formulations of gatifloxacin ophthalmic solution include chemosis, conjunctival hemorrhage, dry eye, eye discharge, eyelid edema, headache, increased lacrimation, keratitis, papillary conjunctivitis, and reduced visual acuity.
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====


<!--Drug Interactions-->
<!--Drug Interactions-->
|drugInteractions=Specific drug interaction studies have not been conducted with ZYMAXID® ophthalmic solution.  
|drugInteractions=* Specific drug interaction studies have not been conducted with ZYMAXID® ophthalmic solution.  


<!--Use in Specific Populations-->
<!--Use in Specific Populations-->
|FDAPregCat=C
|FDAPregCat=C
|useInPregnancyFDA=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 post-implantation loss and neonatal/perinatal mortalities were observed at 200 mg/kg/day (approximately 4000-fold higher than the maximum recommended ophthalmic dose).
|useInPregnancyFDA=* 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 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, ZYMAXID® solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
* Because there are no adequate and well-controlled studies in pregnant women, ZYMAXID® solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''


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* Five (5) mL bottle containing 2.5 mL of a 0.5% sterile topical ophthalmic solution.
* Five (5) mL bottle containing 2.5 mL of a 0.5% sterile topical ophthalmic solution.
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
|monitoring=* There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
 
* Description


<!--IV Compatibility-->
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
|IVCompat=* There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.


<!--Overdosage-->
<!--Overdosage-->
|overdose====Acute Overdose===
====Signs and Symptoms====
* Description
====Management====
* Description
===Chronic Overdose===
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
<!--Pharmacology-->
<!--Drug box 2-->
|drugBox=[[File:Gatifloxacin image.jpg|600px|thumbnail|left]]
|drugBox=[[File:Gatifloxacin image.jpg|600px|thumbnail|left]]
{{clear}}
{{clear}}
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* ZYMAXID® is a clear, pale yellow, sterile, preserved aqueous solution with an osmolality of 260-330 mOsm/kg and a pH of 5.1-5.7.
* ZYMAXID® is a clear, pale yellow, sterile, preserved aqueous solution with an osmolality of 260-330 mOsm/kg and a pH of 5.1-5.7.


* ZYMAXID® contains Active: gatifloxacin 0.5% (5 mg/mL); Inactives: benzalkonium chloride 0.005%; edetate disodium; purified water; and sodium chloride. May contain hydrochloric acid and/or sodium hydroxide to adjust pH.  
* ZYMAXID® contains Active: gatifloxacin 0.5% (5 mg/mL); Inactives: benzalkonium chloride 0.005%; edetate disodium; purified water; and sodium chloride. May contain hydrochloric acid and/or sodium hydroxide to adjust pH.
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
|PD=* There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.


<!--Pharmacokinetics-->
<!--Pharmacokinetics-->
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====Microbiology====
====Microbiology====


Gatifloxacin is an 8-methoxyfluoroquinolone with a 3-methylpiperazinyl substituent at C7. The antibacterial action of 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 gatifloxacin is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, gatifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to gatifloxacin. There is no cross-resistance between gatifloxacin and the aforementioned classes of antibiotics. Cross-resistance has been observed between systemic gatifloxacin and some other fluoroquinolones.
* Gatifloxacin is an 8-methoxyfluoroquinolone with a 3-methylpiperazinyl substituent at C7. The antibacterial action of 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 gatifloxacin is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, gatifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to gatifloxacin. There is no cross-resistance between gatifloxacin and the aforementioned classes of antibiotics. Cross-resistance has been observed between systemic gatifloxacin and some other fluoroquinolones.


Resistance to gatifloxacin in vitro develops via multiple-step mutations. Resistance to gatifloxacin in vitro occurs at a general frequency of 1 x 10-7 to 10-10.
* Resistance to gatifloxacin in vitro develops via multiple-step mutations. Resistance to gatifloxacin in vitro occurs at a general frequency of 1 x 10-7 to 10-10.


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.
* 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:
*Aerobic Gram-Positive Bacteria:


Staphylococcus aureus
*Staphylococcus aureus
Staphylococcus epidermidis
*Staphylococcus epidermidis
Streptococcus mitis group*
*Streptococcus mitis group*
Streptococcus oralis*
*Streptococcus oralis*
Streptococcus pneumoniae
*Streptococcus pneumoniae


Aerobic Gram-Negative Bacteria:
*Aerobic Gram-Negative Bacteria:


Haemophilus influenzae
*Haemophilus influenzae


*Efficacy for this organism was studied in fewer than 10 infections.  
*Efficacy for this organism was studied in fewer than 10 infections.
|nonClinToxic=13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
|nonClinToxic='''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 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.
* 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.
* 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 ZYMAXID®).  
* 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 ZYMAXID®).
|clinicalStudies=* In two randomized, double-masked, multicenter clinical trials, where patients 1-89 years of age were dosed for 5 days, ZYMAXID® 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 gatifloxacin versus 70% (228/325) for vehicle. Please note that microbiological eradication does not always correlate with clinical outcome in anti-infective trials.  
|clinicalStudies=* In two randomized, double-masked, multicenter clinical trials, where patients 1-89 years of age were dosed for 5 days, ZYMAXID® 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 gatifloxacin versus 70% (228/325) for vehicle. Please note that microbiological eradication does not always correlate with clinical outcome in anti-infective trials.
|howSupplied=* ZYMAXID® (gatifloxacin ophthalmic solution) 0.5% is supplied sterile in a white, low density polyethylene (LDPE) bottle with a controlled dropper tip, and a tan, high impact polystyrene (HIPS) cap in the following size:
|howSupplied=* ZYMAXID® (gatifloxacin ophthalmic solution) 0.5% is supplied sterile in a white, low density polyethylene (LDPE) bottle with a controlled dropper tip, and a tan, high impact polystyrene (HIPS) cap in the following size:


* 2.5 mL in 5 mL bottle: NDC 0023-3615-25  
* 2.5 mL in 5 mL bottle: NDC 0023-3615-25
|storage=* Store at 15°-25°C (59°-77°F). Protect from freezing.  
|storage=* Store at 15°-25°C (59°-77°F). Protect from freezing.
|packLabel=[[File:Gatifloxacin pdp.jpg|600px|thumbnail|left]]
|packLabel=[[File:Gatifloxacin pdp.jpg|600px|thumbnail|left]]
{{clear}}
{{clear}}
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[[File:Gatifloxacin label.jpg|600px|thumbnail|left]]
[[File:Gatifloxacin label.jpg|600px|thumbnail|left]]
{{clear}}
{{clear}}
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
|fdaPatientInfo='''Avoiding Contamination of the Product'''
 
*Patients should be instructed to avoid contaminating the applicator tip with material from the eye, fingers, or other source.


<!--Precautions with Alcohol-->
'''Avoidance of Contact Lens Wear'''
 
*Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial conjunctivitis.
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.


<!--Brand Names-->
<!--Brand Names-->
|brandNames=* ®<ref>{{Cite web | title =  | url =  }}</ref>
|brandNames=Tequin,
 
Tequin Teq-Paqs,
<!--Look-Alike Drug Names-->
Zymar,
Zymaxid.
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web  | last =  | first =  | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web  | last =  | first =  | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>


Revision as of 20:32, 2 December 2014

Gatifloxacin
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]

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Black Box Warning

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content

Overview

Gatifloxacin is an anti-infective agent that is FDA approved for the treatment of bacterial conjunctivitis caused by susceptible strains of haemophilus influenzae, staphylococcus aureus, staphylococcus epidermidis, streptococcus mitis group*, streptococcus oralis*, streptococcus pneumoniae. There is a Black Box Warning for this drug as shown here. Common adverse reactions include worsening of conjunctivitis, eye irritation, dysgeusia, and eye pain.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Bacterial conjunctivitis
  • Dosing Information
  • 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.

Off-Label Use and Dosage (Adult)

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Bacterial conjunctivitis
  • Dosing Information
  • 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.

Off-Label Use and Dosage (Pediatric)

Contraindications

None

Warnings

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content

Topical Ophthalmic Use Only

  • ZYMAXID® 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 ZYMAXID® (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, fluorescein 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 ZYMAXID®.

Adverse Reactions

Clinical Trials Experience

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 ZYMAXID®, the most frequently reported adverse reactions occurring in ≥ 1% of patients in the gatifloxacin study population (N=717) were: worsening of the conjunctivitis, eye irritation, dysgeusia, and eye pain.
  • Additional adverse events reported with other formulations of gatifloxacin ophthalmic solution include chemosis, conjunctival hemorrhage, dry eye, eye discharge, eyelid edema, headache, increased lacrimation, keratitis, papillary conjunctivitis, and reduced visual acuity.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Gatifloxacin in the drug label.

Drug Interactions

  • Specific drug interaction studies have not been conducted with ZYMAXID® ophthalmic solution.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): 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 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, ZYMAXID® solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category
  • There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Gatifloxacin in women who are pregnant.

Labor and Delivery

  • There is no FDA guidance on use of Gatifloxacin during labor and delivery.

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 ZYMAXID® is administered to a nursing woman.

Pediatric Use

  • The safety and effectiveness of ZYMAXID® in infants below one year of age have not been established. ZYMAXID® has been demonstrated in clinical trials to be safe and effective for the treatment of bacterial conjunctivitis in pediatric patients one year or older.

Geriatic Use

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

Gender

  • There is no FDA guidance on the use of Gatifloxacin with respect to specific gender populations.

Race

  • There is no FDA guidance on the use of Gatifloxacin with respect to specific racial populations.

Renal Impairment

  • There is no FDA guidance on the use of Gatifloxacin in patients with renal impairment.

Hepatic Impairment

  • There is no FDA guidance on the use of Gatifloxacin in patients with hepatic impairment.

Females of Reproductive Potential and Males

  • There is no FDA guidance on the use of Gatifloxacin in women of reproductive potentials and males.

Immunocompromised Patients

  • There is no FDA guidance one the use of Gatifloxacin in patients who are immunocompromised.

Administration and Monitoring

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.

DOSAGE FORMS AND STRENGTHS

  • Five (5) mL bottle containing 2.5 mL of a 0.5% sterile topical ophthalmic solution.

Monitoring

  • There is limited information regarding Monitoring of Gatifloxacin in the drug label.

IV Compatibility

  • There is limited information regarding IV Compatibility of Gatifloxacin in the drug label.

Overdosage

There is limited information regarding Gatifloxacin overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

File:Gatifloxacin image.jpg

Mechanism of Action

  • Gatifloxacin is a fluoroquinolone antibacterial.

Structure

  • ZYMAXID® 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:
  • ZYMAXID® is a clear, pale yellow, sterile, preserved aqueous solution with an osmolality of 260-330 mOsm/kg and a pH of 5.1-5.7.
  • ZYMAXID® contains Active: gatifloxacin 0.5% (5 mg/mL); Inactives: benzalkonium chloride 0.005%; edetate disodium; purified water; and sodium chloride. May contain hydrochloric acid and/or sodium hydroxide to adjust pH.

Pharmacodynamics

  • There is limited information regarding Pharmacodynamics of Gatifloxacin in the drug label.

Pharmacokinetics

  • 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 gatifloxacin levels were below the lower limit of quantification (5 ng/mL) in all subjects.

Microbiology

  • Gatifloxacin is an 8-methoxyfluoroquinolone with a 3-methylpiperazinyl substituent at C7. The antibacterial action of 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 gatifloxacin is different from that of aminoglycoside, macrolide, and tetracycline antibiotics. Therefore, gatifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to gatifloxacin. There is no cross-resistance between gatifloxacin and the aforementioned classes of antibiotics. Cross-resistance has been observed between systemic gatifloxacin and some other fluoroquinolones.
  • Resistance to gatifloxacin in vitro develops via multiple-step mutations. Resistance to gatifloxacin in vitro occurs at a general frequency of 1 x 10-7 to 10-10.
  • 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.

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 ZYMAXID®).

Clinical Studies

  • In two randomized, double-masked, multicenter clinical trials, where patients 1-89 years of age were dosed for 5 days, ZYMAXID® 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 gatifloxacin versus 70% (228/325) for vehicle. Please note that microbiological eradication does not always correlate with clinical outcome in anti-infective trials.

How Supplied

  • ZYMAXID® (gatifloxacin ophthalmic solution) 0.5% is supplied sterile in a white, low density polyethylene (LDPE) bottle with a controlled dropper tip, and a tan, high impact polystyrene (HIPS) cap in the following size:
  • 2.5 mL in 5 mL bottle: NDC 0023-3615-25

Storage

  • Store at 15°-25°C (59°-77°F). Protect from freezing.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

Avoiding Contamination of the Product

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

Avoidance of Contact Lens Wear

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

Precautions with Alcohol

  • Alcohol-Gatifloxacin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Tequin, Tequin Teq-Paqs, Zymar, Zymaxid.

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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