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Ciprofloxacin Hydrochloride Ophthalmic Solution

TABLE OF CONTENTS

1. DESCRIPTION 7. WARNINGS AND PRECAUTIONS
2. INDICATIONS AND USAGE 8. ADVERSE REACTIONS
3. DOSAGE AND ADMINISTRATION 9. OVERDOSAGE
4. CONTRAINDICATIONS 10. DRUG INTERACTIONS
5. MICROBIOLOGY 11. PHARMACOKINETICS
6. USE IN SPECIFIC POPULATIONS 12. HOW SUPPLIED/STORAGE AND HANDLING

 

1. DESCRIPTION

Ciprofloxacin ophthalmic solution USP, 0.3% is a synthetic, sterile, multiple dose, antimicrobial for topical use. Ciprofloxacin is a fluoroquinolone antibacterial active against a broad spectrum of gram-positive and gram-negative ocular pathogens. Ciprofloxacin hydrochloride, USP is the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8. Its molecular formula is C17H18FN3O3•HCl•H2O 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 USP, 0.3% contains:

ACTIVE: Ciprofloxacin HCl 3.5 mg equivalent to 3 mg base.

PRESERVATIVE ADDED: 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.

2. INDICATIONS AND USAGE

Ciprofloxacin ophthalmic solution USP, 0.3% 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.

3. DOSAGE AND ADMINISTRATION

Corneal Ulcers: The recommended dosage regimen for the treatment of corneal ulcers is 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 conjunctivitis is 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.

4. CONTRAINDICATIONS

Ciprofloxacin tablets are contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.

Concomitant administration with tizanidine is contraindicated. (See Drug Interactions.)

5. MICROBIOLOGY

Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and recombination. The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to ciprofloxacin and other quinolones. There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations.

6. USE IN SPECIFIC POPULATIONS

6.1 Usage in Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies in pregnant women. Ciprofloxacin ophthalmic solution USP, 0.3% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

6.2 Nursing Mothers

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 USP, 0.3% is administered to a nursing mother.

6.3 Pediatric Use

Safety and effectiveness in pediatric patients below the age of 1 year have not been established. 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.

6.4 Geriatric Use

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

7. WARNINGS AND PRECAUTIONS

WARNINGS

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.

PRECAUTIONS

General

As with other antibacterial preparations, prolonged use of ciprofloxacin may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated. Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.

Ciprofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity reaction.

In clinical studies of patients with bacterial corneal ulcer, a white crystalline precipitate located in the superficial portion of the corneal defect was observed in 35 (16.6%) of 210 patients. The onset of the precipitate was within 24 hours to 7 days after starting therapy. In one patient, the precipitate was immediately irrigated out upon its appearance. In 17 patients, resolution of the precipitate was seen in 1 to 8 days (seven within the first 24-72 hours), in five patients, resolution was noted in 10-13 days. In nine patients, exact resolution days were unavailable; however, at follow-up examinations, 18-44 days after onset of the event, complete resolution of the precipitate was noted. In three patients, outcome information was unavailable. The precipitate did not preclude continued use of ciprofloxacin, nor did it adversely affect the clinical course of the ulcer or visual outcome. (SEE ADVERSE REACTIONS).

Information for Patients

Do not touch dropper tip to any surface, as this may contaminate the solution.

8. ADVERSE REACTIONS

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 (SEE PRECAUTIONS).

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.

9. OVERDOSAGE

A topical overdose of ciprofloxacin ophthalmic solution USP, 0.3% may be flushed from the eye(s) with warm tap water.

10. DRUG INTERACTIONS

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

11. PHARMACOKINETICS

Absorption

A systemic absorption study was performed in which ciprofloxacin ophthalmic solution USP, 0.3% 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.

12. HOW SUPPLIED/STORAGE AND HANDLING

1) How Available:

a) Brand name: CILOXAN, by ALCON.

b) Generic drugs: CIPROFLOXACIN HYDROCHLORIDE, by various manufacturers.

2) How Supplied:

Ciprofloxacin ophthalmic solution USP (by Bausch & Lomb): 2.5 mL, 5 mL and 10 mL in LDPE bottles with an LDPE tip and polypropylene cap.

2.5 mL in a 7.5 mL bottle NDC 24208-444-25

5 mL in a 7.5mL bottle NDC 24208-444-05

10 mL in a 10mL bottle NDC 24208-444-10

DO NOT USE IF IMPRINTED NECKBAND IS NOT INTACT.

3) Storage:

Store at 2°-25°C (36°-77°F). Protect from light.

KEEP OUT OF REACH OF CHILDREN.

Rx only

Rev 03/06