CILOXAN® (ciprofloxacin hydrochloride ophthalmic ointment) Ophthalmic Ointment is a synthetic, sterile, multiple dose, antimicrobial for topical use. Ciprofloxacin is a fluoroquinolone antibacterial. It is available as the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7- (1-piperazinyl)-3-quinolinecarboxylic acid. Ciprofloxacin is a faint to light yellow crystalline powder with a molecular weight of 385.82. Its empirical 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 gram ot CILOXAN Ophthalmic Ointment contains:

Active: Ciprofloxacin HCl 3.33 mg equivalent to 3 mg base.
Inactives: Mineral Oil, White Petrolatum.

CILOXAN Ophthalmic Ointment is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the microorganisms listed below:

Gram-Positive:

Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pneumoniae
Streptococcus Viridans Group

Gram-Negative:

Haemophilus influenzae

Apply a 1/2" ribbon into the conjunctival sac three times a day on the first two days, then apply a 1/2" ribbon two times a day for the next five days.

Sterile ophthalmic ointment: 3.5 g ophthalmic ointment tube.

3.5 g NDC 0065-0654-35

Storage: Store at 36° F to 77° F (2° C to 25° C).

Rx Only

The following adverse reactions (incidences) were reported in 2% of the patients in clinical studies for CILOXAN Ophthalmic Ointment: discomfort, keratopathy. Other reactions associated with ciprofloxacin therapy occurring in less than 1% of patients included allergic reactions, blurred vision, corneal staining, decreased visual acuity, dry eye, edema, epitheliopathy, eye pain, foreign body sensation, hyperemia, irritation, keratoconjunctivitis, keratopathy, lid erythema, lid margin hyperemia, photophobia, pruritus, and tearing.

Systemic adverse reactions related to ciprofloxacin therapy occurred at an incidence below 1% and included dermatitis, nausea and taste perversion.

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.

FOR TOPICAL OPHTHALMIC USE ONLY.
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.

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. Ophthalmic ointments may retard corneal healing and cause visual blurring.

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

Information For Patients

See PATIENT INFORMATION section.

Drug Interactions

See DRUG INTERACTIONS section.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Eight in vitro mutagenicity tests have been conducted with ciprofloxacin and the test results are listed below:

Salmonella/Microsome Test (Negative)
E.coli DNA Repair Assay (Negative)
Mouse Lymphoma Cell Forward Mutation Assay (Positive)
Chinese Hamster V79 Cell HGPRT Test (Negative)
Syrian Hamster Embryo Cell Transformation Assay (Negative)
Saccharomyces cerevisiae Point Mutation Assay (Negative)
Saccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative)
Rat Hepatocyte DNA Repair Assay (Positive)

Thus, two of the eight tests were positive, but the results of the following three in vivo test systems gave negative results:

Rat Hepatocyte DNA Repair Assay
Micronucleus Test (Mice)
Dominant Lethal Test (Mice)

Long-term carcinogenicity studies in mice and rats have been completed. After daily oral dosing for up to two years, there is no evidence that ciprofloxacin had any carcinogenic or tumorigenic effects in these species.

Pregnancy

Pregnancy Category C. Reproduction studies have been performed in rats and mice at doses up to six times the usual daily human oral dose and have revealed no evidence of impaired fertility or harm to the fetus due to ciprofloxacin. In rabbits, as with most antimicrobial agents, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion. No teratogenicity was observed at either dose. After intravenous administration, at doses up to 20 mg/kg no maternal toxicity was produced and no embryotoxicity or teratogenicity was observed. There are no adequate and well controlled studies in pregnant women. CILOXAN® Ophthalmic Ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 CILOXAN® Ophthalmic Ointment is administered to a nursing mother.

Pediatric Use

Safety and effectiveness of CILOXAN Ophthalmic Ointment 0.3% in pediatric patients below the age of two years have not been established. Although ciprofloxacin and other quinolones may cause arthropathy in immature Beagle dogs 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 information provided.

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.

Systemic Absorption

Absorption studies in humans with the ciprofloxacin ointment have not been conducted, however, based on studies with ciprofloxacin solution, 0.3%, mean maximal concentrations are expected to be less than 2.5 ng/mL.

Microbiology

Ciprofloxacin has in vitro activity 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 microorganisms both in vitro and in clinical infections (See INDICATIONS section).

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

The following in vitro data are available; but their clinical significance in ophthalmologic infections is unknown.

The safety and effectiveness of ciprofloxacin in treating conjunctivitis due to these microorganisms have not been established in adequate and well controlled trials.

The following 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. Ciprofloxacin exhibits in vitro minimal inhibitory concentrations (MIC's) of 1ng/mL or less (systemic susceptible breakpoint) against most (³90%) strains of the following ocular pathogens.

Aerobic gram-positive microorganisms:

Bacillus species
Corynebacterium species
Staphylococcus haemolyticus
Staphylococcus hominis

Aerobic gram-negative microorganisms:

Acinetobacter calcoaceticus
Enterobacter aerogenes
Escherichia coil
Haemophilus parainfluenzae
Kiebsielle pneumoniae
Moraxella catarrhalis
Neisseria gonorrhoeae
Proteus mirabilis
Pseudomonas aeruginosa
Serratia marcesens

Most strains of Burkholderia cepacia and some strains of Stenotrophomonas maltophilia are resistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides fragilis and 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 vitro usually develops slowly (multiplestep mutation).

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

Clinical Studies

In multicenter clinical trials, approximately 75% of the patients with signs and symptoms of bacterial conjunctivitis and positive conjunctival cultures were clinically cured and approximately 80% had presumed pathogens eradicated by the end of treatment (day 7).

ANIMAL PHARMACOLOGY

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.

Do not touch tip to any surface as this may contaminate the ointment.

See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.

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.

CIPROFLOXACIN OINTMENT - OPHTHALMIC

(sip-row-FLOX-uh-sin)

COMMON BRAND NAME(S): Ciloxan

USES: This medication is used to treat eye infections. Ciprofloxacin belongs to a class of drugs called 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. Unnecessary use or overuse of any antibiotic can lead to its decreased effectiveness.

HOW TO USE: 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 using them.

Apply eye ointment to the affected eye(s) as follows: Wash hands first. To avoid contamination, be careful not to touch the tube tip or let it touch your eye. Tilt your head back, look upward, and pull down your lower eyelid to make a pouch. Place a 1/2 inch (1.5 centimeters) strip of ointment into the pouch by squeezing the tube gently. Look downward and gently close your eyes for 1 to 2 minutes. Roll your eyeball in all directions to spread the medication. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed. Apply as often as directed by your doctor.

Wipe the tip of the ointment tube with a clean tissue to remove excess medication before recapping it.

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

Use this medication regularly in order to get the most benefit from it. Continue using it for the full time prescribed even if symptoms disappear after a few days. Stopping the medication too early may allow bacteria to continue to grow, which may result in a relapse of the infection.

Inform your doctor if your condition persists or worsens.

SIDE EFFECTS: This medication may temporarily sting or burn your eyes for a minute or two when applied. Blurred vision, eye discomfort, itching, redness, tearing, dry eyes, feeling as if something is in your eye, a bad taste in your mouth, or sensitivity to light may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

White crystals may appear in the treated eye(s) after the first few days of ciprofloxacin use, but they usually go away in a few weeks. This effect is harmless. Keep your scheduled appointments so your doctor can closely monitor your eye infection. If you notice any new or worsening eye symptoms (e.g., increased discharge, eye pain), tell your doctor immediately.

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.

Use of this medication for prolonged or repeated periods may result in a new fungal eye infection. Do not use it for longer than prescribed. Contact your doctor if you notice new or worsening symptoms.

Tell your doctor immediately if any of these unlikely but serious side effects occur: staining of the eye, swelling in or around the eye, eye pain, worsening vision.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, 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 ciprofloxacin, tell your doctor or pharmacist if you are allergic to it; or to other quinolones (e.g., levofloxacin, moxifloxacin); or if you have any other allergies.

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

Use caution engaging in activities requiring clear vision, such as driving or using machinery, because your vision may be temporarily blurred or unstable after applying this drug. Limit alcoholic beverages.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known if the medication in this product passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. 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: If 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. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Throw away the unused portion after therapy is completed. Do not use it later for another infection or give it to someone else. A different medication may be necessary in those cases.

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 between 36-77 degrees F (2-25 degrees C) away from light and moisture. Do not freeze. Do not store in the bathroom. 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.