Ciprofloxacin Hydrochloride and Hydrocortisone

INDICATIONS AND USAGE Ciprofloxacin hydrochloride and hydrocortisone otic suspension is indicated for the treatment of acute otitis externa in adult and pediatric patients, one year and older, due to susceptible strains of Pseudomonas aeruginosa , Staphylococcus aureus , and Proteus mirabilis .

DOSAGE AND ADMINISTRATION SHAKE WELL IMMEDIATELY BEFORE USING. For children (age 1 year and older) and adults, 3 drops of the suspension should be instilled into the affected ear twice daily for seven days. The suspension should be warmed by holding the bottle in the hand for 1-2 minutes to avoid the dizziness, which may result from the instillation of a cold solution into the ear canal. The patient should lie with the affected ear upward and then the drops should be instilled. This position should be maintained for 30-60 seconds to facilitate penetration of the drops into the ear. Repeat, if necessary, for the opposite ear. Discard unused portion after therapy is completed.

WARNINGS NOT FOR OPHTHALMIC USE. NOT FOR INJECTION. Ciprofloxacin hydrochloride and hydrocortisone otic suspension should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolones. Serious acute hypersensitivity reactions may require immediate emergency treatment. The dropper cap contains natural rubber (latex) which may cause severe allergic reactions.

CONTRAINDICATIONS Ciprofloxacin hydrochloride and hydrocortisone otic suspension is contraindicated in persons with a history of hypersensitivity to hydrocortisone, ciprofloxacin or any member of the quinolone class of antimicrobial agents. This nonsterile product should not be used if the tympanic membrane is known or suspected to be perforated. Use of this product is contraindicated in viral infections of the external canal including varicella and herpes simplex infections.

ADVERSE REACTIONS In Phase 3 clinical trials, a total of 564 patients were treated with ciprofloxacin hydrochloride and hydrocortisone otic suspension. Adverse events with at least remote relationship to treatment included headache (1.2%) and pruritus (0.4%). The following treatment-related adverse events were each reported in a single patient: migraine, hypesthesia, paresthesia, fungal dermatitis, cough, rash, urticaria, and alopecia. The following reactions have been identified during post-approval use of ciprofloxacin hydrochloride and hydrocortisone otic suspension in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to ciprofloxacin hydrochloride and hydrocortisone otic suspension, or a combination of these factors include: dizziness, ear canal erythema, ear congestion, hypoacusis and medication residue. To report SUSPECTED ADVERSE REACTIONS, contact Cosette Pharmaceuticals, Inc. at 1-800-922-1038 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

CLINICAL PHARMACOLOGY The plasma concentrations of ciprofloxacin were not measured following three drops of otic suspension administration because the systemic exposure to ciprofloxacin is expected to be below the limit of quantitation of the assay (0.05 μg/mL). Similarly, the predicted C max of hydrocortisone is within the range of endogenous hydrocortisone concentration (0-150 ng/mL), and therefore can not be differentiated from the endogenous cortisol. Preclinical studies have shown that ciprofloxacin hydrochloride and hydrocortisone otic suspension was not toxic to the guinea pig cochlea when administered intratympanically twice daily for 30 days and was only weakly irritating to rabbit skin upon repeated exposure. Hydrocortisone has been added to aid in the resolution of the inflammatory response accompanying bacterial infection. Microbiology Ciprofloxacin has in vitro activity against a wide range of gram-positive and gram-negative microorganisms. The bactericidal action of ciprofloxacin results from interference with the enzyme, DNA gyrase, which is needed for the synthesis of bacterial DNA. Cross-resistance has been observed between ciprofloxacin and other fluoroquinolones. There is generally no cross-resistance between ciprofloxacin and other classes of antibacterial agents such as beta-lactams or aminoglycosides. Ciprofloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections of acute otitis externa as described in the INDICATIONS AND USAGE section: Aerobic gram-positive microorganism Staphylococcus aureus Aerobic gram-negative microorganisms Proteus mirabilis Pseudomonas aeruginosa