PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL

NDC 53746-831-53

Ciprofloxacin and Dexamethasone Otic Suspension, USP

0.3%/0.1% (7.5 mL)

Rx only

Container Label

Amneal Pharmaceuticals LLC


NDC 53746-831-53

Ciprofloxacin and Dexamethasone Otic Suspension, USP

0.3%/0.1% (7.5 mL)

Rx only

Carton Label

Amneal Pharmaceuticals LLC


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DESCRIPTION SECTION

11 DESCRIPTION

Ciprofloxacin and Dexamethasone Otic Suspension, USP contains the quinolone antimicrobial, ciprofloxacin hydrochloride, USP, combined with the corticosteroid, dexamethasone USP, in a sterile, preserved suspension for otic use. Each mL of ciprofloxacin and dexamethasone otic suspension, USP contains ciprofloxacin hydrochloride, USP (equivalent to 3 mg ciprofloxacin base), 1 mg dexamethasone, USP, and 0.1 mg benzalkonium chloride as a preservative. The inactive ingredients are acetic acid, boric acid, edetate disodium (as dihydrate), hydroxyethyl cellulose, sodium acetate trihydrate, sodium chloride, tyloxapol and water for injection, USP. Sodium hydroxide or hydrochloric acid may be added for adjustment of pH.

Ciprofloxacin, a quinolone antimicrobial is available as the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid. The molecular formula is C17H18FN3O3·HCl·H2O. The molecular weight is 385.82 g/mol and the structural formula is:

Figure 1: Structure of Ciprofloxacin


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Dexamethasone USP, (11β,16α)-9-fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione, is a corticosteroid. The molecular formula is C22H29FO5. The molecular weight is 392.46 g/mol and the structural formula is:

Figure 2: Structure of Dexamethasone


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INDICATIONS & USAGE SECTION

Highlight: Ciprofloxacin and dexamethasone otic suspension is a combination of ciprofloxacin, a fluoroquinolone antibacterial and dexamethasone, a corticosteroid, indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms in the specific condition listed below:

• Acute Otitis Externa (AOE) in pediatric (age 6 months and older), adult, and elderly patients due to Staphylococcus aureus and Pseudomonas aeruginosa. (1)

1 INDICATIONS AND USAGE

Ciprofloxacin and dexamethasone otic suspension is indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms in the specific condition listed below:

• Acute Otitis Externa (AOE) in pediatric (age 6 months and older), adult and elderly patients due to Staphylococcus aureus and Pseudomonas aeruginosa.

DOSAGE FORMS & STRENGTHS SECTION

Highlight: Otic Suspension: Each mL of ciprofloxacin and dexamethasone otic suspension, USP contains ciprofloxacin hydrochloride USP, 0.3% (equivalent to 3 mg ciprofloxacin base) and dexamethasone USP, 0.1% (equivalent to 1 mg dexamethasone, USP). (3)

3 DOSAGE FORMS AND STRENGTHS

Ciprofloxacin and dexamethasone otic suspension, USP: Each mL contains ciprofloxacin hydrochloride USP, 0.3% (equivalent to 3 mg ciprofloxacin base) and dexamethasone USP, 0.1% (equivalent to 1 mg dexamethasone, USP).

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CONTRAINDICATIONS SECTION

Highlight: * Ciprofloxacin and dexamethasone otic suspension is contraindicated in patients with a history of hypersensitivity to ciprofloxacin, to other quinolones, or to any of the components in this medication. (4)

• Use of this product is contraindicated in viral infections of the external canal, including herpes simplex infections and fungal otic infections. (4)

4 CONTRAINDICATIONS

• Ciprofloxacin and dexamethasone otic suspension is contraindicated in patients with a history of hypersensitivity to ciprofloxacin, to other quinolones, or to any of the components in this medication.
• Use of this product is contraindicated in viral infections of the external canal, including herpes simplex infections and fungal otic infections.

WARNINGS AND PRECAUTIONS SECTION

Highlight: * Hypersensitivity and anaphylaxis have been reported with systemic use of quinolones. Discontinue use if this occurs with use of ciprofloxacin and dexamethasone. (5.1)

• Prolonged use may result in overgrowth of non-susceptible bacteria and fungi. (5.2)

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Ciprofloxacin and dexamethasone 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. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal, or facial edema), airway obstruction, dyspnea, urticaria, and itching.

5.2 Potential for Microbial Overgrowth with Prolonged Use

Prolonged use of ciprofloxacin and dexamethasone otic suspension may result in overgrowth of non-susceptible bacteria and fungi. If the infection is not improved after one week of treatment, cultures should be obtained to guide further treatment. If such infections occur, discontinue use and institute alternative therapy.

5.3 Continued or Recurrent Otorrhea

If otorrhea persists after a full course of therapy, or if two or more episodes of otorrhea occur within six months, further evaluation is recommended to exclude an underlying condition, such as cholesteatoma, foreign body, or a tumor.

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USE IN SPECIFIC POPULATIONS SECTION

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on ciprofloxacin and dexamethasone otic suspension use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Because of the minimal systemic absorption of ciprofloxacin and dexamethasone following topical otic administration of ciprofloxacin and dexamethasone otic suspension, this product is expected to be of minimal risk for maternal and fetal toxicity when administered to pregnant women [see Clinical Pharmacology (12.3)].

Animal reproduction studies have not been conducted with ciprofloxacin and dexamethasone otic suspension. Oral administration of ciprofloxacin during organogenesis at doses up to 100 mg/kg to pregnant mice and rats, and up to 30 mg/kg to pregnant rabbits did not cause fetal malformations (see Data). These doses were at least 200 times the recommended otic human dose (ROHD in mice, rats, and rabbits, respectively, based on body surface area (BSA). With dexamethasone, malformations have been observed in animal studies after ocular and systemic administration.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and of miscarriage is 15% to 20% respectively.

Data

Animal Data

Ciprofloxacin

Developmental toxicology studies have been performed with ciprofloxacin in rats, mice, and rabbits. The doses used in these studies are, at a minimum, approximately 200 times greater than the recommended otic human dose based on body surface area. In rats and mice, oral doses up to 100 mg/kg administered during organogenesis (Gestation Days (GD), 6 to 17) were not associated with adverse developmental outcomes, including embryo-fetal toxicity or malformations. A 30 mg/kg oral dose was associated with suppression of maternal and fetal body weight gain, but fetal malformations were not observed. Intravenous administration of doses up to 20 mg/kg to pregnant rabbits was not maternally toxic and neither embryofetal toxicity nor fetal malformations were observed. To mitigate maternal toxicity in these studies, groups of rabbits received ciprofloxacin for a different 5 day dosing period covering organogenesis (GD 6 to 18).

Dexamethasone

Dexamethasone has been shown to be teratogenic in mice and rabbits following topical ophthalmic application. In a rat oral developmental toxicity study, no adverse effects were observed at 0.01 mg/kg/day (0.1 times the ROHD based on BSA), although embryotoxicity was observed at higher doses.

8.2 Lactation

Risk Summary

It is not known whether ciprofloxacin and dexamethasone are present in human milk following topical otic administration.

Published literature reports the presence of ciprofloxacin in human milk after oral administration to lactating women. However, because of the minimal systemic absorption of ciprofloxacin following topical otic administration of ciprofloxacin and dexamethasone otic suspension, breastfeeding is not expected to result in the exposure of the infant to ciprofloxacin [see Clinical Pharmacology (12.3)].

Systemically administered corticosteroids appear in human milk. Dexamethasone in breast milk could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. However, it is not known whether topical otic administration of ciprofloxacin and dexamethasone otic suspension could result in systemic absorption that is sufficient to produce detectable quantities of dexamethasone in human milk.

There are no data on the effects of ciprofloxacin or dexamethasone on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ciprofloxacin and dexamethasone otic suspension and any potential adverse effects on the breast-fed child from ciprofloxacin and dexamethasone otic suspension.

8.4 Pediatric Use

The safety and efficacy of ciprofloxacin and dexamethasone otic suspension have been established in pediatric patients 6 months and older (537 patients) in adequate and well-controlled clinical trials.

No clinically relevant changes in hearing function were observed in 69 pediatric patients (age 4 to 12 years) treated with ciprofloxacin and dexamethasone otic suspension and tested for audiometric parameters.

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CLINICAL STUDIES SECTION

14 CLINICAL STUDIES

In 2 randomized multicenter, controlled clinical trials, ciprofloxacin and dexamethasone otic suspension dosed 2 times per day for 7 days demonstrated clinical cures in 87% and 94% of per protocol evaluable AOE patients, respectively, compared to 84% and 89%, respectively, for otic suspension containing neomycin 0.35%, polymyxin B 10,000 units/mL, and hydrocortisone 1.0% (neo/poly/HC). Among culture-positive patients clinical cures were 86% and 92% for ciprofloxacin and dexamethasone otic suspension compared to 84% and 89%, respectively, for neo/poly/HC. Microbiological eradication rates for these patients in the same clinical trials were 86% and 92% for ciprofloxacin and dexamethasone otic suspension compared to 85% and 85%, respectively, for neo/poly/HC.

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OVERDOSAGE SECTION

10 OVERDOSAGE

Due to the characteristics of this preparation, no toxic effects are to be expected with an otic overdose of this product.

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SPL PATIENT PACKAGE INSERT SECTION

PATIENT INFORMATION

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HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Ciprofloxacin 0.3%****and Dexamethasone 0.1%****Otic Suspension, USP, is a sterile white to off white homogenous suspension supplied as 7.5 mL fill in a system consisting of a 10 mL LDPE natural bottle, 30 µL LDPE natural nozzle and a HDPE white opaque screw-on cap with tamper evident ring for tamper evident feature.

It is available as follows:

7.5 mL in a 10 mL Container: NDC 53746-831-53

Storage

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

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INSTRUCTIONS FOR USE SECTION

INSTRUCTIONS FOR USE

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