Chibroxin

CHIBROXIN (norfloxacin) Ophthalmic Solution is a clear, colorless to light yellow solution.

No. 3526 CHIBROXIN (norfloxacin) Ophthalmic Solution 0.3% is supplied in a white, opaque, plastic OCUMETER* ophthalmic dispenser with a controlled drop tip as follows:

NDC 0006-3526-03, 5 mL.

Storage

Store CHIBROXIN (norfloxacin) Ophthalmic Solution at room temperature, 15°-30°C (59°-86°F). Protect from light.

*Registered trademark of MERCK & CO., INC.

CHIBROXIN (norfloxacin) Ophthalmic Solution is indicated for the treatment of conjunctivitis when caused by susceptible strains of the following bacteria:

Acinetobacter calcoaceticus**

Aeromonas hydrophila**

Haemophilus influenzae

Proteus mirabilis**

Pseudomonas aeruginosa**

Serratia marcescens**

Staphylococcus aureus

Staphylococcus epidermidis

Staphylococcus warnerii**

Streptococcus pneumoniae

Appropriate monitoring of bacterial response to topical antibiotic therapy should accompany the use of CHIBROXIN (norfloxacin) Ophthalmic Solution.

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

The recommended dose in adults and pediatric patients (one year and older) is one or two drops of CHIBROXIN (norfloxacin) Ophthalmic Solution applied topically to the affected eye(s) four times daily for up to seven days. Depending on the severity of the infection, the dosage for the first day of therapy may be one or two drops every two hours during the waking hours.

CHIBROXIN (norfloxacin) Ophthalmic Solution is contraindicated in patients with a history of hypersensitivity to norfloxacin, or the other members of the quinolone group of antibacterial agents or any other component of this medication.

WARNINGS

NOT FOR INJECTION INTO THE EYE.

Serious and occasionally fatal hypersensitivity (anaphylactoid or 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 anaphylactoid or anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids and airway management, including intubation, should be administered as indicated.

PRECAUTIONS

General

As with other antibiotic preparations, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate measures 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.

There have been reports of bacterial keratitis associated with the use of multiple dose containers of topical ophthalmic products. These containers have been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. (See Information for Patients.)

Carcinogenesis, Mutagenesis, Impairment of Fertility

No increase in neoplastic changes was observed with norfloxacin as compared to controls in a study in rats, lasting up to 96 weeks at doses eight to nine times the usual human oral dose***.

Norfloxacin was tested for mutagenic activity in a number of in vivo and in vitro tests. Norfloxacin had no mutagenic effect in the dominant lethal test in mice and did not cause chromosomal aberrations in hamsters or rats at doses 30 to 60 times the usual oral dose***. Norfloxacin had no mutagenic activity in vitro in the Ames microbial mutagen test, Chinese hamster fibroblasts and V-79 mammalian cell assay. Although norfloxacin was weakly positive in the Rec-assay for DNA repair, all other mutagenic assays were negative including a more sensitive test (V-79).

Norfloxacin did not adversely affect the fertility of male and female mice at oral doses up to 33 times the usual human oral dose***.

Pregnancy

Teratogenic Effects Pregnancy Category C.  Norfloxacin has been shown to produce embryonic loss in monkeys when given in doses 10 times the maximum human oral dose*** (400 mg b.i.d.), with peak plasma levels that are two to three times those obtained in humans. There has been no evidence of a teratogenic effect in any of the animal species tested (rat, rabbit, mouse, monkey) at 6 to 50 times the human oral dose. There are no adequate and well-controlled studies in pregnant women. CHIBROXIN (norfloxacin) Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether norfloxacin is excreted in human milk following ocular administration. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from norfloxacin, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see ANIMAL PHARMACOLOGY).

Pediatric Use

Safety and effectiveness in infants below the age of one year have not been established.

Although quinolones including norfloxacin have been shown to cause arthropathy in immature animals after oral administration, topical ocular administration of other quinolones to immature animals has not shown any arthropathy and there is no evidence that the ophthalmic dosage form of those quinolones has any effects on the weight-bearing joints.

Geriatric Use

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

***All factors are based on a standard patient weight of 50 kg. The usual oral dose of norfloxacin is 800 mg daily. One drop of CHIBROXIN (norfloxacin) Ophthalmic Solution 0.3% contains about 1/6,666 of this dose (0.12 mg).

SIDE EFFECTS

In clinical trials, the most frequently reported drug-related adverse reaction was local burning or discomfort. Other drug-related adverse reactions were conjunctival hyperemia, chemosis, photophobia and a bitter taste following instillation.

DRUG INTERACTIONS

Specific drug interaction studies have not been conducted with norfloxacin ophthalmic solution. 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. Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with norfloxacin. Therefore, cyclosporine serum levels should be monitored and appropriate cyclosporine dosage adjustments made when these drugs are used concomitantly.

In clinical trials, the most frequently reported drug-related adverse reaction was local burning or discomfort. Other drug-related adverse reactions were conjunctival hyperemia, chemosis, photophobia and a bitter taste following instillation.

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain

• R52.1 – Chronic intractable pain
• R52.2 – Other chronic pain
• R52.9 – Unspecified pain