Levofloxacin 10% Mylan

Levofloxacin 10% Mylan® solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:

Gram-positive Bacteria

Corynebacterium species*
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumonia
Streptococcus (Groups C/F)
Streptococcus (Group G)
Viridans group streptococci*

Gram-negative Bacteria

Acinetobacter lwoffii *
Haemophilus influenzae
Serratia marcescens*

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

QUIXIN® solution is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:

Gram-positive Bacteria

Corynebacterium species*
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumonia
Streptococcus (Groups C/F)
Streptococcus (Group G)
Viridans group streptococci*

Gram-negative Bacteria

Acinetobacter lwoffii *
Haemophilus influenzae
Serratia marcescens*

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

Levofloxacin 10% Mylan® solution is contraindicated in patients with a history of hypersensitivity to levofloxacin, to other quinolones, or to any of the components in this medication.

QUIXIN® solution is contraindicated in patients with a history of hypersensitivity to levofloxacin, to other quinolones, or to any of the components in this medication.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypersensitivity Reactions

In patients receiving systemically administered quinolones, including levofloxacin, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema, (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria and itching. If allergic reaction to levofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.

Growth Of Resistant Organisms With Prolonged Use

As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible 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.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a long term carcinogenicity study in rats, levofloxacin exhibited no carcinogenic or tumorigenic potential following daily dietary administration for 2 years at doses up to 100 mg/kg/day, corresponding to plasma levels that were 1235 times the maximum clinical exposure, based on Cmax.

Levofloxacin was not mutagenic in the following assays: Ames bacterial mutation assay (S. typhimurium and E. coli), CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis assay, and the in vivo mouse sister chromatid exchange assay. It was positive in the in vitro chromosomal aberration (CHL cell line) and in vitro sister chromatid exchange (CHL/IU cell line) assays. Levofloxacin caused no impairment of fertility or reproduction in rats at oral doses as high as 360 mg/kg/day, at which systemic exposure was estimated to be 23,000 times that at the maximum recommended human ophthalmic dose.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Teratogenic Effects

Levofloxacin at oral doses of 810 mg/kg/day in rats caused decreased fetal body weight and increased fetal mortality. No teratogenic effect was observed when rabbits were dosed orally as high as 50 mg/kg/day, at which systemic exposure was approximately 2,250 times that observed at the maximum recommended human ophthalmic dose, or when dosed intravenously as high as 25 mg/kg/day, at which systemic exposure was approximately 1000 times that observed at the maximum recommended human ophthalmic dose.

There are, however, no adequate and well-controlled studies in pregnant women. Levofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Levofloxacin has not been measured in human milk. Based upon data from ofloxacin, it can be presumed that levofloxacin is excreted in human milk. Caution should be exercised when Levofloxacin 10% Mylan® is administered to a nursing mother.

Pediatric Use

Safety and effectiveness in children below the age of six years have not been established. Oral administration of systemic quinolones has been shown to cause arthropathy in immature animals. There is no evidence that the ophthalmic administration of levofloxacin has any effect on weight bearing joints.

Geriatric Use

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

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Hypersensitivity Reactions

In patients receiving systemically administered quinolones, including levofloxacin, serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported, some following the first dose. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema, (including laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria and itching. If allergic reaction to levofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management should be administered as clinically indicated.

Growth Of Resistant Organisms With Prolonged Use

As with other anti-infectives, prolonged use may result in overgrowth of non-susceptible 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.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a long term carcinogenicity study in rats, levofloxacin exhibited no carcinogenic or tumorigenic potential following daily dietary administration for 2 years at doses up to 100 mg/kg/day, corresponding to plasma levels that were 1235 times the maximum clinical exposure, based on Cmax.

Levofloxacin was not mutagenic in the following assays: Ames bacterial mutation assay (S. typhimurium and E. coli), CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis assay, and the in vivo mouse sister chromatid exchange assay. It was positive in the in vitro chromosomal aberration (CHL cell line) and in vitro sister chromatid exchange (CHL/IU cell line) assays. Levofloxacin caused no impairment of fertility or reproduction in rats at oral doses as high as 360 mg/kg/day, at which systemic exposure was estimated to be 23,000 times that at the maximum recommended human ophthalmic dose.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Teratogenic Effects

Levofloxacin at oral doses of 810 mg/kg/day in rats caused decreased fetal body weight and increased fetal mortality. No teratogenic effect was observed when rabbits were dosed orally as high as 50 mg/kg/day, at which systemic exposure was approximately 2,250 times that observed at the maximum recommended human ophthalmic dose, or when dosed intravenously as high as 25 mg/kg/day, at which systemic exposure was approximately 1000 times that observed at the maximum recommended human ophthalmic dose.

There are, however, no adequate and well-controlled studies in pregnant women. Levofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Levofloxacin has not been measured in human milk. Based upon data from ofloxacin, it can be presumed that levofloxacin is excreted in human milk. Caution should be exercised when QUIXIN® is administered to a nursing mother.

Pediatric Use

Safety and effectiveness in children below the age of six years have not been established. Oral administration of systemic quinolones has been shown to cause arthropathy in immature animals. There is no evidence that the ophthalmic administration of levofloxacin has any effect on weight bearing joints.

Geriatric Use

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

Levofloxacin concentration in plasma was measured in 15 healthy adult volunteers at various time points during a 15-day course of treatment with Levofloxacin 10% Mylan® solution. The mean levofloxacin concentration in plasma 1 hour postdose, ranged from 0.86 ng/mL on Day 1 to 2.05 ng/mL on Day 15. The highest maximum mean levofloxacin concentration of 2.25 ng/mL was measured on Day 4 following 2 days of dosing every 2 hours for a total of 8 doses per day. Maximum mean levofloxacin concentrations increased from 0.94 ng/mL on Day 1 to 2.15 ng/mL on Day 15, which is more than 1,000 times lower than those reported after standard oral doses of levofloxacin.

Levofloxacin concentration in tears was measured in 30 healthy adult volunteers at various time points following instillation of a single drop of Levofloxacin 10% Mylan® solution. Mean levofloxacin concentrations in tears ranged from 34.9 to 221.1 mcg/mL during the 60-minute period following the single dose. The mean tear concentrations measured 4 and 6 hours postdose were 17.0 and 6.6 mcg/mL. The clinical significance of these concentrations is unknown.

Levofloxacin concentration in plasma was measured in 15 healthy adult volunteers at various time points during a 15-day course of treatment with QUIXIN® solution. The mean levofloxacin concentration in plasma 1 hour postdose, ranged from 0.86 ng/mL on Day 1 to 2.05 ng/mL on Day 15. The highest maximum mean levofloxacin concentration of 2.25 ng/mL was measured on Day 4 following 2 days of dosing every 2 hours for a total of 8 doses per day. Maximum mean levofloxacin concentrations increased from 0.94 ng/mL on Day 1 to 2.15 ng/mL on Day 15, which is more than 1,000 times lower than those reported after standard oral doses of levofloxacin.

Levofloxacin concentration in tears was measured in 30 healthy adult volunteers at various time points following instillation of a single drop of QUIXIN® solution. Mean levofloxacin concentrations in tears ranged from 34.9 to 221.1 mcg/mL during the 60-minute period following the single dose. The mean tear concentrations measured 4 and 6 hours postdose were 17.0 and 6.6 mcg/mL. The clinical significance of these concentrations is unknown.