NDC 42571-168 Levofloxacin

Levofloxacin

NDC Product Code 42571-168

NDC Product Information

Levofloxacin with NDC 42571-168 is a a human prescription drug product labeled by Micro Labs Limited. The generic name of Levofloxacin is levofloxacin. The product's dosage form is solution/ drops and is administered via ophthalmic form.

Labeler Name: Micro Labs Limited

Dosage Form: Solution/ Drops - A solution which is usually administered in a drop-wise fashion.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Levofloxacin Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • LEVOFLOXACIN 15 mg/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • GLYCERIN (UNII: PDC6A3C0OX)
  • HYDROCHLORIC ACID (UNII: QTT17582CB)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Ophthalmic - Administration to the external eye.

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Micro Labs Limited
Labeler Code: 42571
FDA Application Number: ANDA205600 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 04-16-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Levofloxacin Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Levofloxacin ophthalmic solution is indicated for the treatment of corneal ulcer caused by susceptible strains of the following bacteria:


Gram-positive bacteria: Corynebacterium species


Staphylococcus aureus Staphylococcus epidermidis Streptococcus pneumonia Viridans group streptococci*


Gram-negative bacteria: Pseudomonas aeruginosaSerratia marcescens**Efficacy for this organism was studied in fewer than 10 infections

2 Dosage And Administration

Days 1 through 3:Instill one to two drops in the affected eye(s) every 30 minutes to 2 hours while awake and approximately 4 and 6 hours after retiring.Day 4 through treatment completion:Instill one to two drops in the affected eye(s) very 1 to 4 hours while awake.

3 Dosage Forms And Strengths

5 cc bottle filled with 5 mL sterile ophthalmic solution of levofloxacin, 1.5%.

4 Contraindications

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

5.1 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 an 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.

5.2 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.

5.3 Avoidance Of Contact Lens Wear

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

6 Adverse Reactions

The most frequently reported adverse reactions in the overall study population were headache and a taste disturbance following instillation. These reactions occurred in approximately 8 to 10% of patients. Adverse reactions occurring in approximately 1 to 2% of patients included decreased/blurred vision, diarrhea, dyspepsia, fever, infection, instillation site irritation/discomfort, ocular infection, nausea, ocular pain/discomfort, and throat irritation. Other reported ocular reactions occurring in less than 1% of patients included chemosis, corneal erosion, diplopia, floaters, hyperemia, lid edema, and lid erythema.

8.1 Pregnancy

Pregnancy Category CTeratogenic 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 estimated to be 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 estimated to be 120 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.

8.3 Nursing Mothers

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

8.4 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.

8.5 Geriatric Use

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

11 Description

Levofloxacin ophthalmic solution 1.5% is a sterile topical ophthalmic solution. Levofloxacin is a fluoroquinolone antibacterial active against a broad spectrum of Gram-positive and Gram-negative ocular pathogens. Levofloxacin is a fluorinated 4-quinolone containing a six-member (pyridobenzoxazine) ring from positions 1 to 8 of the basic ring structure. Levofloxacin is the pure (-)-(


S)-enantiomer of the racemic drug substance, ofloxacin. It is more soluble in water at neutral pH than ofloxacin.


C


18H


20FN


3O


4 ·½ H2O            Mol Wt 370.38


Chemical Name: (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7


H- pyrido[1,2,3-


de]-1,4 benzoxazine-6-carboxylic acid hemihydrate. Levofloxacin (hemihydrate) USP is a yellowish-white crystalline powder. Each mL of levofloxacin ophthalmic solution contains 15.36 mg of levofloxacin hemihydrate USP equivalent to 15 mg levofloxacin.


Contains: Active: Levofloxacin (hemihydrate) USP is a light yellowish-white;


Inactives: glycerin and water for injection. May also contain hydrochloric acid and/or sodium hydroxide to adjust pH to approximately 6.7. Levofloxacin ophthalmic solution is isotonic with an osmolality of approximately 291 mOsm/kg.

12.1 Mechanism Of Action

Levofloxacin is a member of the fluoroquinolone class of anti-microbial drug


(See 


12.4 Microbiology)


.

12.3 Pharmacokinetics

Levofloxacin concentration in plasma was measured in 14 healthy adult volunteers during a 16-day course of treatment with levofloxacin ophthalmic solution. The dosing schedule was 1 to 2 drops per eye once in the morning on Days 1 and 16; 1 to 2 drops per eye every two hours Days 2 through 8; and 1 to 2 per eye every four hours Days 9 through 15. The mean levofloxacin concentration in plasma 1 hour post dose ranged from 3.13 ng/mL on Day 1 to 10.4 ng/mL on Day 16.Maximum mean levofloxacin concentrations increased from 3.22 ng/mL on Day 1 to 10.9 ng/mL on Day 16, which is more than 400 times lower than those reported after standard oral doses of levofloxacin.Levofloxacin concentration in tears was measured in 100 healthy adult volunteers at various time points following instillation of 2 drops of levofloxacin ophthalmic solution. Mean tear concentration measured 15 minutes after instillation was 757 mcg/mL.

12.4 Microbiology

Levofloxacin is the


L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the


L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves the inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair, and recombination.


Levofloxacin has


in vitro activity against a wide range of Gram-negative and Gram-positive microorganisms and is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.


Fluoroquinolones, including levofloxacin, differ in chemical structure and mode of action from ß-lactam antibiotics and aminoglycosides, and therefore may be active against bacteria resistant to ß-lactam antibiotics and aminoglycosides. Additionally, ß-lactam antibiotics and aminoglycosides may be active against bacteria resistant to levofloxacin. Resistance to levofloxacin due to spontaneous mutation


in vitro is a rare occurrence (range: 10


- 9 to 10


- 10).


Levofloxacin has been shown to be active against most strains of the following microorganisms, both


in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.


Aerobic gram-positive microorganisms:Corynebacterium species*Staphylococcus aureusStaphylococcus epidermidisStreptococcus pneumoniae Viridans group streptococci*Aerobic gram-negative microorganisms:Pseudomonas aeruginosaSerratia marcescens**Efficacy for this organism was studied in fewer than 10 infections.The following


in vitro data are also available, but their clinical significance in ophthalmic infections is unknown.  The safety and effectiveness of levofloxacin in treating ophthalmological infections due to these microorganisms have not been established in adequate and well controlled trials.


These organisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the


in vitro systemic breakpoint and ophthalmological efficacy has not been established. The list of organisms is provided as guidance only in assessing the potential treatment of corneal ulcer. Levofloxacin exhibits


in vitro minimal inhibitory concentrations (MICs) of 2 mcg/mL or less (systemic susceptible breakpoint) against most (≥ 90%) strains of the following ocular pathogens:


Aerobic gram-positive microorganisms:Enterococcus faecalis (many strains are only moderately susceptible)Staphylococcus saprophyticusStreptococcus agalactiae Streptococcus pyogenesStreptococcus (Group C/F)Streptococcus (Group G)Aerobic gram-negative microorganisms:Acinetobacter baumannii Acinetobacter lwoffiiCitrobacter koseriCitrobacter freundiiEnterobacter aerogenesEnterobacter cloacaeEscherichia coliHaemophilus influenzae Haemophilus parainfluenzaeKlebsiella oxytocaKlebsiella pneumoniaLegionella pneumophila Moraxella catarrhalisMorganella morganiiNeisseria gonorrhoeae Pantoea agglomerans Proteus mirabilis Proteus vulgarisProvidencia rettgeri Providencia stuartiiPseudomonas fluorescens

13.1 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 245 times maximum clinical exposure, based on C


max.


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 2,600 times that at the maximum recommended human ophthalmic dose.

14 Clinical Studies

In two randomized, double-masked, multi-center, controlled clinical trials of 280 patients with positive cultures, subjects were dosed with levofloxacin or ofloxacin 0.3% ophthalmic solution.Dosing occurred on Days 1 through 3 every two hours while awake and 4 and 6 hours after retiring. Dosing occurred on Day 4 through treatment completion 4 times daily while awake. Clinical cure was defined as complete re-epithelialization and no progression of the infiltrate for two consecutive visits. The levofloxacin treated subjects had an approximately equal mean clinical cure rate of 80% (73% to 87%) compared to 84% (82% to 86%) for the subjects treated with ofloxacin 0.3% ophthalmic solution.

16 How Supplied/Storage And Handling

Levofloxacin ophthalmic solution 1.5% is supplied in a sterile with a white opaque cylindrical shaped low density polyethylene bottle with an open white opaque cone shaped low density polyethylene controlled dropper tip and a tan color cone shaped high density polyethylene cap in the following size: 5 mL fill in 5 cc container– NDC 42571-168-25Storage: Store at 15° to 25°C (59° to 77°F).

17.1 Avoid Contamination Of The Product

Advise patients to avoid contaminating the applicator tip with material from the eye, finger, or other source.

17.2 Avoid Contact Lens Wear

Advise patients not to wear contact lenses if they have signs and symptoms of corneal ulcer.

17.3 Hypersensitivity Reactions

Systemically administered quinolones, including levofloxacin, have been associated with hypersensitivity reactions, even following a single dose. Advise patients to discontinue use immediately and contact their physician at the first sign of a rash or allergic reactions.

Instructions For Use

Before you use Levofloxacin Ophthalmic Solution for the first time: 1. Check to make sure that the tamper evident ring between the bottle and the cap is not broken (


See Figure A). If the tamper evident ring is broken or missing, contact your pharmacist.


   2. Tear off the tamper evident ring (


See Figure B).


 


3. To open the bottle, remove the cap by turning it in the counterclockwise direction (


See Figure C).


 


This Instructions for Use has been approved by the U.S. Food and Drug Administration.Manufactured by:Micro Labs LimitedBanglore-560099. INDIA.Manufactured for:Micro Labs USA Inc.


Basking Ridge, NJ 07920

* Please review the disclaimer below.

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