CIPRO

CIPRO ^® HC OTIC (ciprofloxacin hydrochloride and hydrocortisone otic suspension) contains the synthetic broad spectrum antibacterial agent, ciprofloxacin hydrochloride, combined with the anti-inflammatory corticosteroid, hydrocortisone, in a preserved, nonsterile suspension for otic use. Each mL of CIPRO ^® HC OTIC contains ciprofloxacin hydrochloride (equivalent to 2 mg ciprofloxacin), 10 mg hydrocortisone, and 9 mg benzyl alcohol as a preservative. The inactive ingredients are polyvinyl alcohol, sodium chloride, sodium acetate, glacial acetic acid, phospholipon 90H (modified lecithin), polysorbate, and purified water. Sodium hydroxide or hydrochloric acid may be added for adjustment of pH.

Ciprofloxacin, a fluoroquinolone, is available as the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C ₁₇H ₁₈FN ₃O ₃•HCI•H ₂O and its chemical structure is as follows:

Ciprofloxacin chemical structure

Hydrocortisone, pregn-4-ene-3, 20-dione, 11, 17, 21-trihydroxy-(11(β)-, is an anti-inflammatory corticosteroid. Its empirical formula is C ₂₁H ₃₀O ₅ and its chemical structure is:

Hydrocortisone chemical structure

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 cannot be differentiated from the endogenous cortisol.

Preclinical studies have shown that CIPRO ^® HC OTIC 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

CIPRO ^® HC OTIC 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.

CIPRO ^® HC OTIC 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.

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.

The safety and efficacy of CIPRO ^® HC OTIC have been established in pediatric patients 2 years and older (131 patients) in adequate and well-controlled clinical trials. Efficacy has been extrapolated for patients, age 1 year and above based on studies in adults and older pediatric patients.

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.

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.

CIPRO ^® HC OTIC is supplied as a white to off-white opaque suspension in a 10 mL bottle with a dropper dispenser:

NDC 76420-273-10  (relabeled from NDC 0078-0855-26).

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Avoid freezing. Protect from light.

Relabeled by:

Enovachem PHARMACEUTICALS

Torrance, CA 90501