QUIXIN® (levofloxacin ophthalmic solution) 0.5% 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 the pure (-)-(S)-enantiomer of the racemic drug substance, ofloxacin. It is more soluble in water at neutral pH than ofloxacin.

Structural Formula

Levofloxacin hemihydrate
C₁₈H₂₀FN₃O₄•½H₂O     Mol Weight 370.38

Chemical Name:

(-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4 benzoxazine-6-carboxylic acid hemihydrate.

Levofloxacin (hemihydrate) is a yellowish-white crystalline powder.

Each mL of QUIXIN® contains 5.12 mg of levofloxacin hemihydrate equivalent to 5 mg levofloxacin.

Contains:

Active: Levofloxacin 0.5% (5 mg/mL); Preservative: benzalkonium chloride 0.005%; Inactives: sodium chloride and water. May also contain hydrochloric acid and/or sodium hydroxide to adjust pH.

QUIXIN® solution is isotonic and formulated at pH 6.5 with an osmolality of approximately 300 mOsm/kg. Levofloxacin is a fluorinated 4-quinolone containing a six-member (pyridobenzoxazine) ring from positions 1 to 8 of the basic ring structure.

Last updated on RxList: 12/18/2008

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

AEROBIC GRAM-POSITIVE MICROORGANISMS	AEROBIC GRAM-NEGATIVE MICROORGANISMS
Corynebacterium species*	Acinetobacter Iwoffii*
Staphylococcus aureus	Haemophilus influenzae
Staphylococcus epidermidis	Serratia marcescens*
Streptococcus pneumoniae
Streptococcus (Groups C/F)
Streptococcus (Group G)
Viridans group streptococci
*Efficacy for this organism was studied in fewer than 10 infections.

Days 1 and 2

Instill one to two drops in the affected eye(s) every 2 hours while awake, up to 8 times per day.

Days 3 through 7

Instill one to two drops in the affected eye(s) every 4 hours while awake, up to 4 times per day.

QUIXIN® (levofloxacin ophthalmic solution) 0.5% is supplied in a white, low density polyethylene bottle with a controlled dropper tip and a tan, high density polyethylene cap in the following size: 5 mL fill in 5 cc container - NDC 68669-135-05

Storage

Store at 15° – 25°C (59° – 77°F).

Manufactured by: Santen Oy, P. O. Box 33, FIN-33721 Tampere, Finland. Licensed from: Daiichi Sankyo Co., Ltd., Tokyo, Japan. Marketed by: VISTAKON® Pharmaceuticals, LLC Jacksonville, FL 32256 USA. April 2006 Version. FDA revision date: 4/11/2005

Last updated on RxList: 12/18/2008

The most frequently reported adverse events in the overall study population were transient decreased vision, fever, foreign body sensation, headache, transient ocular burning, ocular pain or discomfort, pharyngitis and photophobia. These events occurred in approximately 1-3% of patients. Other reported reactions occurring in less than 1% of patients included allergic reactions, lid edema, ocular dryness, and ocular itching.

Specific drug interaction studies have not been conducted with QUIXIN®. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, and enhance the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with transientelevations in serum creatinine in patients receiving systemic cyclosporine concomitantly.

Last updated on RxList: 12/18/2008

NOT FOR INJECTION.

QUIXIN® solution should not be injected subconjunctivally, nor should it be introduced directly into the anterior chamber of the eye.

In patients receiving systemic quinolones, 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.

General

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 slitlamp biomicroscopy, and, where appropriate, fluorescein staining.

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

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; the highest dose (100 mg/kg/day) was 875 times the highest recommended human ophthalmic dose.

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, corresponding to 3,150 times the highest recommended human ophthalmic dose.

Pregnancy

Teratogenic Effects. Pregnancy Category C

Levofloxacin at oral doses of 810 mg/kg/day in rats, which corresponds to approximately 7,000 times the highest recommended human ophthalmic dose, 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, which corresponds to approximately 400 times the highest recommended maximum human ophthalmic dose, or when dosed intravenously as high as 25 mg/kg/day, corresponding to approximately 200 times the highest 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 infants below the age of one year have not been established. Oral administration of 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.

Last updated on RxList: 12/18/2008

No information provided.

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.

Last updated on RxList: 12/18/2008

Pharmacokinetics

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 μg/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 μg/mL. The clinical significance of these concentrations is unknown.

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 β-lactam antibiotics and aminoglycosides, and therefore may be active against bacteria resistant to β-lactam antibiotics and aminoglycosides. Additionally, β-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	AEROBIC GRAM-NEGATIVE A MICROORGANISMS
Corynebacterium species*	Acinetobacter lwoffii*
Staphylococcus aureus	Haemophilus influenzae
Staphylococcus epidermidis	Serratia marcescens*
Streptococcus pneumoniae
Streptococcus (Groups C/F)
Streptococcus (Group G)
Viridans group streptococci
*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 conjunctival infections. Levofloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 2 μg/mL or less (systemic susceptible breakpoint) against most ( ≥ 90%) strains of the following ocular pathogens.

AEROBIC GRAM-POSITIVE MICROORGANISMS
Enterococcus faecalis	Streptococcus agalactiae
Staphylococcus saprophyticus	Streptococcus pyogenes
AEROBIC GRAM-NEGATIVE A MICROORGANISMS
Acinetobacter anitratus	Legionella pneumophila
Acinetobacter baumannii	Moraxella catarrhalis
Citrobacter diversus	Morganella morganii
Citrobacter freundii	Neisseria gonorrhoeae
Enterobacter aerogenes	Proteus mirabilis
Enterobacter agglomerans	Proteus vulgaris
Enterobacter cloacae	Providencia rettgeri
Escherichia coli	Providencia stuartii
Haemophilus parainfluenzae	Pseudomonas aeruginosa
Klebsiella oxytoca	Pseudomonas fluorescens
Klebsiella pneumoniae

Clinical Studies

In randomized, double-masked, multicenter controlled clinical trials where patients were dosed for 5 days, QUIXIN® demonstrated clinical cures in 79% of patients treated for bacterial conjunctivitis on the final study visit day (day 6-10). Microbial outcomes for the same clinical trials demonstrated an eradication rate for presumed pathogens of 90%.

Last updated on RxList: 12/18/2008

Avoid contaminating the applicator tip with material from the eye, fingers or other source. Systemic quinolones have been associated with hypersensitivity reactions, even following a single dose. Discontinue use immediately and contact your physician at the first sign of a rash or allergic reaction.

Last updated on RxList: 12/18/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

LEVOFLOXACIN - OPHTHALMIC DROPS

(lev-oh-FLOX-uh-sin)

COMMON BRAND NAME(S): Quixin

USES: This medication is used to treat bacterial eye infections. Levofloxacin belongs to a class of drugs known as quinolone antibiotics. It works by stopping the growth of bacteria.

This medication treats only bacterial eye infections. It will not work for other types of eye infections (e.g., infections caused by viruses, fungi, mycobacteria). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

HOW TO USE: This medication is applied to the eye(s) as directed by your doctor. To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

Do not wear contact lenses while you are using this medicine. Sterilize contact lenses according to manufacturer's directions, and check with your doctor before you begin using them again.

Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps if your dose is for more than 1 drop and for your other eye if so directed. Repeat as often as directed by your doctor. Your dosage is based on your medical condition and response to treatment.

Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e.g., drops or ointments), wait at least 5 minutes before applying other medications. Use eye drops before eye ointments to allow the drops to enter the eye.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same times each day. Continue using it for the full time prescribed, even if symptoms disappear after a few days. Stopping the medication too soon may allow the bacteria to continue to grow, which may result in a return of the infection.

Tell your doctor immediately if your condition does not improve in a few days or if you develop new or worsening eye symptoms (e.g., discharge, swelling, redness, pain).

SIDE EFFECTS: Temporary blurred or decreased vision, temporary stinging/burning/pain in the eyes, feeling as if something is in the eye, sensitivity of the eyes to light, fever, headache, or sore throat may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, itching/swelling/redness of the eye/eyelid, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using levofloxacin, tell your doctor or pharmacist if you are allergic to it; or to other quinolone antibiotics (e.g., ciprofloxacin, norfloxacin); or to preservatives (e.g., benzalkonium chloride); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: other eye problems.

After you apply this drug, your vision may become temporarily blurred or unstable. Use caution while driving, using machinery, or doing any other activity that requires clear vision.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Based on information from related drugs, this medication may pass into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medicine may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Throw away the unused portion after treatment is completed. Do not use it later for another infection. A different medication may be necessary in that case.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature between 59-77 degrees F (15-25 degrees C) away from heat, light, and moisture. Do not store in the bathroom. Throw away this medication and do not use it if the solution turns brown or cloudy or contains particles. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.