Label: CIPROFLOXACIN HYDROCHLORIDE solution/ drops

Ciprofloxacin ophthalmic solution is a synthetic, sterile, multiple dose, antimicrobial for topical ophthalmic use. Ciprofloxacin is a fluoroquinolone antibacterial active against a broad spectrum of gram-positive and gram-negative ocular pathogens. It is available as the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1- piperazinyl)-3-quinoline-carboxylic acid. It is a faint to light yellow crystalline powder with a molecular weight of 385.8. Its empirical formula is C 17H 18FN 3O 3∙HCl∙H 2O and its chemical structure is as follows:

Ciprofloxacin differs from other quinolones in that it has a fluorine atom at the 6-position, a piperazine moiety at the 7-position, and a cyclopropyl ring at the 1-position.

Each mL of ciprofloxacin ophthalmic solution contains: Active:ciprofloxacin HCl 3.5 mg equivalent to 3 mg base. Preservative:benzalkonium chloride 0.006%. Inactives:sodium acetate, acetic acid, mannitol 4.6%, edetate disodium 0.05%, hydrochloric acid and/or sodium hydroxide (to adjust pH) and purified water. The pH is approximately 4.5 and the osmolality is approximately 300 mOsm.

Systemic Absorption

A systemic absorption study was performed in which ciprofloxacin ophthalmic solution was administered in each eye every two hours while awake for two days followed by every four hours while awake for an additional 5 days. The maximum reported plasma concentration of ciprofloxacin was less than 5 ng/mL. The mean concentration was usually less than 2.5 ng/mL.

Microbiology

Ciprofloxacin has in vitroactivity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of ciprofloxacin results from interference with the enzyme DNA gyrase which is needed for the synthesis of bacterial DNA.

Ciprofloxacin has been shown to be active against most strains of the following organisms both in vitroand in clinical infections [seeIndications and Usage]:

Aerobic gram-positive microorganisms:

Staphylococcus aureus(methicillin-susceptible strains)

Staphylococcus epidermidis(methicillin-susceptible strains)

Streptococcus pneumoniae

Streptococcus(Viridans Group)

Aerobic gram-negative microorganisms:

Haemophilus influenzae

Pseudomonas aeruginosa

Serratia marcescens

Ciprofloxacin has been shown to be active in vitroagainst most strains of the following organisms, however, the clinical significance of these data is unknown:

Gram-Positive:

Enterococcus faecalis(Many strains are only moderately susceptible)

Staphylococcus haemolyticus

Staphylococcus hominis

Staphylococcus saprophyticus

Streptococcus pyogenes

Gram-Negative:

Acinetobacter

calcoaceticus subsp.

1. anitratus

Aeromonas caviae

Aeromonas hydrophila

Brucella melitensis

Campylobacter coli

Campylobacter jejuni

Citrobacter diversus

Citrobacter freundii

Edwardsiella tarda

Enterobacter aerogenes

Enterobacter cloacae

Escherichia coli

Haemophilus ducreyi

Haemophilus parainfluenzae

Klebsiella pneumoniae

Klebsiella oxytoca

Legionella pneumophila

Moraxella

1. (Branhamella)
2. catarrhalis

Morganella morganii

Neisseria gonorrhoeae

Neisseria meningitidis

Pasteurella multocida

Proteus mirabilis

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Salmonella enteritidis

Salmonella typhi

Shigella sonneii

Shigella flexneri

Vibrio cholerae

Vibrio

1. parahaemolyticus

Vibrio vulnificus

Yersinia enterocolitica

Other Organisms

Chlamydia trachomatis(only moderately susceptible) and Mycobacterium tuberculosis(only moderately susceptible).

Most strains of Pseudomonas cepaciaand some strains of Pseudomonas maltophiliaare resistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides fragilisand Clostridium difficile.

The minimal bactericidal concentration (MBC) generally does not exceed the minimal inhibitory concentration (MIC) by more than a factor of 2. Resistance to ciprofloxacin in vitrousually develops slowly (multiple-step mutation).

Ciprofloxacin does not cross-react with other antimicrobial agents such as beta-lactams or aminoglycosides; therefore, organisms resistant to these drugs may be susceptible to ciprofloxacin.

Ciprofloxacin ophthalmic solution is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

Corneal Ulcers:

Pseudomonas aeruginosa

Serratia marcescens*

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus pneumoniae

Streptococcus(Viridans Group)*

Conjunctivitis:

Haemophilus influenzae

Staphylococcus aureus

Staphylococcus epidermidis

Streptococcus pneumoniae

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

A history of hypersensitivity to ciprofloxacin or any other component of the medication is a contraindication to its use. A history of hypersensitivity to other quinolones may also contraindicate the use of ciprofloxacin.

NOT FOR INJECTION INTO THE EYE.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Only a few patients had a history of hypersensitivity reactions. Serious anaphylactic reactions require immediate emergency treatment with epinephrine and other resuscitation measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines and airway management, as clinically indicated.

Remove contact lenses before using.

It is not known whether topically applied ciprofloxacin is excreted in human milk; however, it is known that orally administered ciprofloxacin is excreted in the milk of lactating rats and oral ciprofloxacin has been reported in human breast milk after a single 500 mg dose. Caution should be exercised when ciprofloxacin ophthalmic solution is administered to a nursing mother.

The safety and effectiveness of ciprofloxacin ophthalmic solution 0.3% have been established in all ages. Use of ciprofloxacin ophthalmic solution is supported by evidence from adequate and well controlled studies of ciprofloxacin ophthalmic solution in adults, children and neonates [see Clinical Studies]. Although ciprofloxacin and other quinolones cause arthropathy in immature animals after oral administration, topical ocular administration of ciprofloxacin to immature animals did not cause any arthropathy and there is no evidence that the ophthalmic dosage form has any effect on the weight bearing joints.

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

The most frequently reported drug related adverse reaction was local burning or discomfort. In corneal ulcer studies with frequent administration of the drug, white crystalline precipitates were seen in approximately 17% of patients [seePrecautions].Other reactions occurring in less than 10% of patients included lid margin crusting, crystals/scales, foreign body sensation, itching, conjunctival hyperemia and a bad taste following instillation. Additional events occurring in less than 1% of patients included corneal staining, keratopathy/keratitis, allergic reactions, lid edema, tearing, photophobia, corneal infiltrates, nausea and decreased vision.

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.

A topical overdose of ciprofloxacin ophthalmic solution may be flushed from the eye(s) with warm tap water.

Corneal Ulcers

The recommended dosage regimen for the treatment of corneal ulcersis two drops into the affected eye every 15 minutes for the first six hours and then two drops into the affected eye every 30 minutes for the remainder of the first day. On the second day, instill two drops in the affected eye hourly. On the third through the fourteenth day, place two drops in the affected eye every four hours. Treatment may be continued after 14 days if corneal re-epithelialization has not occurred.

Bacterial Conjunctivitis

The recommended dosage regimen for the treatment of bacterial conjunctivitisis one or two drops instilled into the conjunctival sac(s) every two hours while awake for two days and one or two drops every four hours while awake for the next five days.

As a sterile ophthalmic solution in Alcon’s DROP-TAINER ®dispensing system consisting of a natural low density polyethylene bottle and dispensing plug and tan polypropylene closure. Tamper evidence is provided with a shrink band around the closure and neck area of the package.

2.5 mL in 8mL bottle NDC76420-942-03 (relabeled from NDC 61314-656-25)

5 mL in 8mL bottle NDC76420-942-05 (relabeled from NDC 61314-656-05)

10 mL in 10mL bottle NDC76420-942-10 (relabeled from NDC 61314-656-10)

STORAGEStore at 2° to 25°C (36° to 77°F). Protect from light.

Ciprofloxacin and related drugs have been shown to cause arthropathy in immature animals of most species tested following oral administration. However, a one-month topical ocular study using immature Beagle dogs did not demonstrate any articular lesions.

Following therapy with ciprofloxacin ophthalmic solution, 76% of the patients with corneal ulcers and positive bacterial cultures were clinically cured and complete re-epithelialization occurred in about 92% of the ulcers.

In 3 and 7 day multicenter clinical trials, 52% of the patients with conjunctivitis and positive conjunctival cultures were clinically cured and 70% to 80% had all causative pathogens eradicated by the end of treatment.

In a randomized, double-masked, multicenter, parallel-group clinical trial of pediatric patients with bacterial conjunctivitis, between birth and 31 days of age, patients were dosed with ciprofloxacin or another anti-infective agent. Clinical outcomes for the trial demonstrated a clinical cure rate of 80% at Day 9 and a microbiological eradication success rate of 85% at Day 9.

Please note that microbiologic eradication does not always correlate with clinical outcome in anti-infective trials.

Rx Only

Relabeled by:

Enovachem PHARMACEUTICALS

Torrance, CA 90501