CIPRO HC ciprofloxacin hydrochloride and hydrocortisone 2 mg/mL; 10 mg/mL Suspension/ Drops — NDC 66758-087-70 (Billing 66758-0087-70)

WARNINGS NOT FOR OPHTHALMIC USE. NOT FOR INJECTION. CIPRO ® HC OTIC 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.

ADVERSE REACTIONS In Phase 3 clinical trials, a total of 564 patients were treated with CIPRO ® HC OTIC. 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 CIPRO ® HC OTIC 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 CIPRO ® HC OTIC, or a combination of these factors, include: dizziness, ear canal erythema, ear congestion, hypoacusis, and medication residue.

PRECAUTIONS General: As with other antibiotic preparations, use of this product may result in overgrowth of nonsusceptible organisms, including fungi. If the infection is not improved after one week of therapy, cultures should be obtained to guide further treatment. Information for Patients: If rash or allergic reaction occurs, discontinue use immediately and contact your physician.

Do not use in the eyes. Avoid contaminating the dropper with material from the ear, fingers, or other sources. Protect from light.

Shake well immediately before using. Discard unused portion after therapy is completed. 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 V 79 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, 2 of the 8 tests were positive, but results of the following 3 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 for ciprofloxacin.

After daily oral doses of 750 mg/kg (mice) and 250 mg/kg (rats) were administered for up to 2 years, there was no evidence that ciprofloxacin had any carcinogenic or tumorigenic effects in these species. No long-term studies of CIPRO ® HC OTIC suspension have been performed to evaluate carcinogenic potential. Fertility studies performed in rats at oral doses of ciprofloxacin up to 100 mg/kg/day revealed no evidence of impairment.

This would be over 1000 times the maximum recommended clinical dose of ototopical ciprofloxacin based upon body surface area, assuming total absorption of ciprofloxacin from the ear of a patient treated with CIPRO ® HC OTIC twice per day. Long-term studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical hydrocortisone. Mutagenicity studies with hydrocortisone were negative.

Pregnancy: Teratogenic Effects: Reproduction studies have been performed in rats and mice using oral doses of up to 100 mg/kg and IV doses up to 30 mg/kg and have revealed no evidence of harm to the fetus as a result of ciprofloxacin. In rabbits, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion, but no teratogenicity was observed at either dose. After intravenous administration of doses up to 20 mg/kg, no maternal toxicity was produced in the rabbit, and no embryotoxicity or teratogenicity was observed.

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. Animal reproduction studies have not been conducted with CIPRO ® HC OTIC.

No adequate and well-controlled studies have been performed in pregnant women. Caution should be exercised when CIPRO ® HC OTIC is used by a pregnant woman. Nursing Mothers: Ciprofloxacin is excreted in human milk with systemic use.

It is not known whether ciprofloxacin is excreted in human milk following topical otic administration. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.