NDC 52536-080 Ciprofloxacin And Fluocinolone Acetonide

Ciprofloxacin And Fluocinolone Acetonide

NDC Product Code 52536-080

NDC CODE: 52536-080

Proprietary Name: Ciprofloxacin And Fluocinolone Acetonide What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Ciprofloxacin And Fluocinolone Acetonide What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to treat a variety of bacterial infections. Ciprofloxacin belongs to a class of drugs called quinolone antibiotics. It works by stopping the growth of bacteria. This antibiotic treats only bacterial infections. It will not work for virus infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.
  • This shampoo is used to treat severe dandruff (seborrheic dermatitis). Fluocinolone reduces the swelling, itching, flaking, and redness that can occur with dandruff. This medication is a low- to medium-strength corticosteroid.

NDC Code Structure

  • 52536 - Wilshire Pharmaceuticals
    • 52536-080 - Ciprofloxacin And Fluocinolone Acetonide

NDC 52536-080-14

Package Description: 1 POUCH in 1 CARTON > 14 VIAL, SINGLE-DOSE in 1 POUCH > .25 mL in 1 VIAL, SINGLE-DOSE

NDC Product Information

Ciprofloxacin And Fluocinolone Acetonide with NDC 52536-080 is a a human prescription drug product labeled by Wilshire Pharmaceuticals. The generic name of Ciprofloxacin And Fluocinolone Acetonide is ciprofloxacin and fluocinolone acetonide. The product's dosage form is solution and is administered via auricular (otic) form.

Labeler Name: Wilshire Pharmaceuticals

Dosage Form: Solution - A clear, homogeneous liquid1 dosage form that contains one or more chemical substances dissolved in a solvent or mixture of mutually miscible solvents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Ciprofloxacin And Fluocinolone Acetonide Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CIPROFLOXACIN .75 mg/.25mL
  • FLUOCINOLONE ACETONIDE .0625 mg/.25mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • GLYCERIN (UNII: PDC6A3C0OX)
  • POLYSORBATE 80 (UNII: 6OZP39ZG8H)
  • POVIDONE K90 (UNII: RDH86HJV5Z)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Auricular (otic) - Administration to or by way of the ear.
  • Auricular (otic) - Administration to or by way of the ear.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Quinolone Antimicrobial - [EPC] (Established Pharmacologic Class)
  • Quinolones - [CS]
  • Corticosteroid - [EPC] (Established Pharmacologic Class)
  • Corticosteroid Hormone Receptor Agonists - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Wilshire Pharmaceuticals
Labeler Code: 52536
FDA Application Number: NDA208251 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 11-01-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Ciprofloxacin And Fluocinolone Acetonide Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Ciprofloxacin and Fluocinolone Acetonide Otic Solution is indicated for the treatment of acute otitis media with tympanostomy tubes (AOMT) in pediatric patients (aged 6 months and older) due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa.

2 Dosage And Administration

  • Ciprofloxacin and Fluocinolone Acetonide Otic Solution is for otic use only. It is not for ophthalmic use, or for injection.The recommended dosage regimen is as follows:Instill the contents of one single-dose vial 0.25 mL into the affected ear canal twice daily (approximately every 12 hours) for 7 days. Use this dosing for patients aged 6 months of age and older.Warm the solution by holding the vial in the hand for 1 to 2 minutes. This is to avoid 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 instill the medication.Pump the tragus 4 times by pushing inward to facilitate penetration of the medication into the middle ear.Maintain this position for 1 minute. Repeat, if necessary, for the opposite ear [see Instructions for Use].

3 Dosage Forms And Strengths

Otic Solution: Each single-dose vial of Ciprofloxacin and Fluocinolone Acetonide Otic Solution (ciprofloxacin 0.3 % and fluocinolone acetonide 0.025 %) delivers 0.25 mL of solution equivalent to ciprofloxacin 0.75 mg and fluocinolone acetonide 0.0625 mg.

4 Contraindications

  • Ciprofloxacin and Fluocinolone Acetonide Otic Solution is contraindicated in:Patients with known hypersensitivity to fluocinolone acetonide or other corticosteroids, ciprofloxacin or other quinolones, or to any other components of Ciprofloxacin and Fluocinolone Acetonide Otic Solution.Viral infections of the external ear canal, including varicella and herpes simplex infections and fungal otic infections.

5.1 Hypersensitivity Reactions

Ciprofloxacin and Fluocinolone Acetonide Otic Solution 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. Serious acute hypersensitivity reactions may require immediate emergency treatment.

5.2 Potential For Microbial Overgrowth With Prolonged Use

Prolonged use of Ciprofloxacin and Fluocinolone Acetonide Otic Solution 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 6 months, further evaluation is recommended to exclude an underlying condition such as cholesteatoma, foreign body, or a tumor.

6 Adverse Reactions

The following serious adverse reactions are described elsewhere in the labeling:Hypersensitivity Reactions [see Warnings and Precautions (5.1)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.In clinical trials, 224 patients with AOMT were treated with Ciprofloxacin and Fluocinolone Acetonide Otic Solution for a median duration of 7 days. All the patients received at least one dose of Ciprofloxacin and Fluocinolone Acetonide Otic Solution. There were 220 patients who received at least one dose of ciprofloxacin (CIPRO) and 213 patients received at least one dose of fluocinolone acetonide (FLUO).The most common adverse reactions that occurred in 1 or more patients are as follows:Table 1: Selected Adverse Reactions that Occurred in 1 or more Patients in the Ciprofloxacin and Fluocinolone Acetonide Otic Solution GroupAdverse ReactionsSelected adverse reactions that occurred in ≥ 1 patient in the Ciprofloxacin and Fluocinolone Acetonide Otic Solution group derived from all reported adverse events that could be related to the study drug or the drug class.Number (%) of PatientsCiprofloxacin and Fluocinolone Acetonide Otic SolutionN=224CIPRON=220FLUON=213Otorrhea12 (5.4%)9 (4.1%)12 (5.6%)Excessive granulation tissue3 (1.3%)0 (0.0%)2 (0.9%)Ear infection2 (0.9%)3 (1.4%)1 (0.5%)Ear pruritus2 (0.9%)1 (0.5%)1 (0.5%)Tympanic membrane disorder2 (0.9%)0 (0.0%)0 (0.0%)Auricular swelling1 (0.4%)1 (0.5%)0 (0.0%)Balance disorder1 (0.4%)0 (0.0%)0 (0.0%)

6.2 Postmarketing Experience

  • The following adverse reactions have been identified during postapproval use of ciprofloxacin and fluocinolone acetonide otic solution, 0.3% / 0.025% outside the US. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Immune system disorders: allergic reaction.Infections and infestations: candidiasis.Nervous system disorders: dysgeusia, paresthesia (tingling in ears), dizziness, headache.Ear and labyrinth disorders: ear discomfort, hypoacusis, tinnitus, ear congestion.Vascular disorders: flushing.Skin and subcutaneous tissue disorders: skin exfoliation.Injury, poisoning and procedural complications: device occlusion (tympanostomy tube obstruction).

Other

Risk SummaryCiprofloxacin and Fluocinolone Acetonide Otic Solution is negligibly absorbed following otic administration and maternal use is not expected to result in fetal exposure to ciprofloxacin and fluocinolone acetonide [see Clinical Pharmacology (12.3)].

Risk SummaryCiprofloxacin and Fluocinolone Acetonide Otic Solution is negligibly absorbed by the mother following otic administration and breastfeeding is not expected to result in exposure of the infant to ciprofloxacin and fluocinolone acetonide [see Clinical Pharmacology (12.3)].

Mechanism of ActionThe bactericidal action of ciprofloxacin results from interference with the enzyme DNA gyrase, which is needed for the synthesis of bacterial DNA.

ResistanceBacterial resistance to quinolones can develop through chromosomal or plasmid-mediated mechanisms. In vitro studies demonstrated cross-resistance between ciprofloxacin and some fluoroquinolones. There is generally no cross-resistance between ciprofloxacin and other classes of antibacterial agents such as beta-lactams or aminoglycosides.

Antimicrobial ActivityCiprofloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and clinically in otic infections [see Indications and Usage (1)]:

Aerobic Bacteria:Gram-positive Bacteria:Staphylococcus aureusStreptococcus pneumoniaeGram-negative Bacteria:Pseudomonas aeruginosaHaemophilus influenzaeMoraxella catarrhalis

CarcinogenesisNo long term studies of Ciprofloxacin and Fluocinolone Acetonide Otic Solution have been performed to evaluate carcinogenic potential.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.Long-term animal studies have not been performed to evaluate the carcinogenic potential of fluocinolone acetonide.

  • MutagenesisEight 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 V79 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 AssayMicronucleus Test (Mice)Dominant Lethal Test (Mice)Studies have not been performed to evaluate the mutagenic potential of fluocinolone acetonide. Some corticosteroids have been found to be genotoxic.

Impairment of FertilityNo reproduction toxicity studies were conducted with Ciprofloxacin and Fluocinolone Acetonide Otic Solution. Absorption of ciprofloxacin and fluocinolone acetonide following otic administration of Ciprofloxacin and Fluocinolone Acetonide Otic Solution at the recommended dosage is negligible [see Clinical Pharmacology (12.3)].

How suppliedCiprofloxacin and Fluocinolone Acetonide Otic Solution, 0.3 %/0.025 %, is a sterile, preservative-free, clear otic solution supplied in blue translucent single-dose 0.25 mL vials. Fourteen single-dose vials are packaged in a protective foil pouch contained in a carton (NDC 52536-080-14).

  • Administration InstructionsAdvise patients that Ciprofloxacin and Fluocinolone Acetonide Otic Solution is for otic use only. It is not to be used in the eyes.Advise patients to warm the otic solution by holding the vial in the hand for 1 to 2 minutes before instilling it in the ear, to avoid dizziness.

  • Hypersensitivity ReactionsAdvise patients to immediately discontinue Ciprofloxacin and Fluocinolone Acetonide Otic Solution at the first appearance of a skin rash or any other sign of hypersensitivity [see Warnings and Precautions (5.1)]

Ciprofloxacin and Fluocinolone Acetonide Otic Solution is:Distributed by:Wilshire Pharmaceuticals, Inc.Atlanta, GA 30328Under license of Laboratorios SALVAT, S.A.U.S. Patent No: 8,932,610OTO-PIAG-00

8.4 Pediatric Use

Ciprofloxacin and Fluocinolone Acetonide Otic Solution has been studied in patients as young as 6 months in adequate and well-controlled clinical trials. No major differences in safety and effectiveness have been observed between adult and pediatric patients [see Indications and Usage (1) and Dosage and Administration (2)].

8.5 Geriatric Use

Clinical studies of Ciprofloxacin and Fluocinolone Acetonide Otic Solution did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

10 Overdosage

Due to the characteristics of this preparation, no toxic effects are to be expected with an otic overdose of Ciprofloxacin and Fluocinolone Acetonide Otic Solution.

11 Description

Ciprofloxacin and Fluocinolone Acetonide Otic Solution, 0.3% / 0.025% is a sterile, preservative-free, clear otic solution containing the fluoroquinolone antibacterial, ciprofloxacin hydrochloride, combined with the corticosteroid, fluocinolone acetonide. Each single-dose vial contains a deliverable volume of 0.25 mL solution of ciprofloxacin hydrochloride equivalent to 0.75 mg ciprofloxacin and 0.0625 mg fluocinolone acetonide. The pH of the solution ranges from 3.5 to 5.0. The inactive ingredients are polysorbate 80, glycerin, povidone K90F and water for injection.Ciprofloxacin is available as the monohydrochloride, monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its molecular formula is C17H18FN3O3∙HCl∙H2O.The chemical structure of ciprofloxacin hydrochloride is:The chemical name of fluocinolone acetonide is (6α,11β,16α)-6,9-difluoro-11,21-dihydroxy- 16,17[(1-methylethylidene)bis(oxy)]-pregna-1,4-diene-3,20-dione, cyclic 16,17 acetal with acetone[67-73-2]. Its molecular formula is C24H30F2O6.The chemical structure of fluocinolone acetonide is:

12.1 Mechanism Of Action

Ciprofloxacin is a fluoroquinolone antibacterial [see Microbiology (12.4)].Fluocinolone acetonide, a corticosteroid, inhibits the local biosynthesis of prostaglandins, which explains part of its anti-inflammatory efficacy. At the cellular level, corticosteroids induce peptides called lipocortins. Lipocortins antagonize phospholipase A2, an enzyme which causes the breakdown of leukocyte lysosomal membranes to release arachidonic acid. This action decreases the subsequent formation and release of endogenous inflammatory mediators including prostaglandins, kinins, histamine, liposomal enzymes and the complement system.

12.3 Pharmacokinetics

In two studies in children with AOMT aged ≥ 6 months to 12 years, blood samples were taken in subgroups of 16 and 14 patients, at Visit 1 (prior to the first dose) and Visit 3 (within 1 and 2 hours after the last dose) respectively, to determine the plasma concentrations of ciprofloxacin and/or fluocinolone acetonide following administration of Ciprofloxacin and Fluocinolone Acetonide Otic Solution at the recommended dosage regimen of 0.25 mL twice daily. Pharmacokinetic (PK) analysis resulted in only 1 sample showing a detectable concentration of ciprofloxacin in plasma of 3.0 mcg/L after 7 days of treatment, and no detectable concentrations in plasma of fluocinolone acetonide were observed. However, the sample with detectable ciprofloxacin concentrations was from a patient who had bilateral AOMT (protocol deviation because all patients participating in the PK study were to have unilateral otorrhea) and who received treatment in both ears with ciprofloxacin 0.3% otic solution, the active comparator.

14 Clinical Studies

Two phase 3 multicenter, randomized, double-blind, active-controlled, parallel group trials were conducted in 662 pediatric patients in total (aged 6 months to 12 years old) with AOMT, to assess the efficacy and safety of Ciprofloxacin and Fluocinolone Acetonide Otic Solution compared to ciprofloxacin otic solution and to fluocinolone acetonide otic solution (Trial 1 and Trial 2).In both trials, the Ciprofloxacin and Fluocinolone Acetonide Otic Solution treatment arms showed significantly shorter times to cessation of otorrhea in comparison to both the ciprofloxacin and fluocinolone acetonide alone arms demonstrating the contribution of both components of Ciprofloxacin and Fluocinolone Acetonide Otic Solution. The results are presented in the table below:Table 2: Results of the Primary Endpoint: Time to Cessation of Otorrhea (Trial 1 and Trial 2)Treatment armn.e.: not estimable because the number of censored patients was greater than the number of patients with cessation of otorrheaTrial 1Ciprofloxacin and Fluocinolone Acetonide Otic Solution(N=112)CIPRO(N=109) FLUO(N=110)Number (%) with cessation of otorrhea by Day 2288 (78.6%)73 (67.0%)53 (48.2%)Median time to cessationKaplan-Meier median estimate censored all subjects who did not have a cessation of otorrhea at the maximum time point of 22 days. (days)3.757.69n.e.p-value vs Ciprofloxacin and Fluocinolone Acetonide Otic SolutionLog-rank test stratified by age (patients younger than 3 years versus 3 years and older)<0.001<0.001 Trial 2Ciprofloxacin and Fluocinolone Acetonide Otic Solution(N=111)CIPRO(N=112)FLUO(N=108)Number (%) with cessation of otorrhea by Day 2287 (78.4%)77 (68.8%)47 (43.5%)Median time to cessation (days)4.946.83n.e.p-value vs Ciprofloxacin and Fluocinolone Acetonide Otic Solution0.028<0.001

Storage And Handling

StorageStore at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from light; store unused vials in pouch and discard 7 days after opening the pouch. Do not open until ready to use. Discard vial after use.

17 Patient Counseling Information

Advise the patient or caregiver to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Instructions For Useciprofloxacin And Fluocinolone Acetonide(Sip-Roh-Flok-Suh-Sin And Floo-Oh-Sin-Oh-Lone Uh-Seet-Oh-Nide)Otic Solution

  • Read this Instructions for Use that comes with Ciprofloxacin and Fluocinolone Acetonide Otic Solution before you start using it and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or treatment.Important information about Ciprofloxacin and Fluocinolone Acetonide Otic Solution:Ciprofloxacin and Fluocinolone Acetonide Otic Solution is for use in the ear only (otic use). Do not inject Ciprofloxacin and Fluocinolone Acetonide Otic Solution or use Ciprofloxacin and Fluocinolone Acetonide Otic Solution in the eye.Use Ciprofloxacin and Fluocinolone Acetonide Otic Solution exactly as your healthcare provider tells you to use it.How should I use Ciprofloxacin and Fluocinolone Acetonide Otic Solution?Step 1.You or your caregiver should wash their hands with soap and water.Step 2.Gently clean any fluid (discharge) from the outer ear using a clean cloth or tissue. Do not put a cotton swab or any other object in the ear canal.Step 3.Remove Ciprofloxacin and Fluocinolone Acetonide Otic Solution from the protective foil pouch. Pull apart 1 single-dose vial of Ciprofloxacin and Fluocinolone Acetonide Otic Solution as shown, by tearing along the dotted lines (perforations) until it is fully separated.Step 4.Warm the dose of Ciprofloxacin and Fluocinolone Acetonide Otic Solution by holding the vial in your hand for 1 to 2 minutes.Step 5.Twist off the vial cap in the direction of the arrow as shown.Step 6.The person receiving Ciprofloxacin and Fluocinolone Acetonide Otic Solution should be on his/her side with the infected ear up as shown. Step 7.Hold the vial of Ciprofloxacin and Fluocinolone Acetonide Otic Solution in your hand and place the vial close to the ear. Let the entire dose of Ciprofloxacin and Fluocinolone Acetonide Otic Solution fall into the affected ear.Step 8.Gently press the part of the ear known as the tragus 4 times using a pumping motion as shown. This will allow the drops of Ciprofloxacin and Fluocinolone Acetonide Otic Solution to enter the middle ear.Step 9.Remain on your side with the affected ear facing upward for 1 minute.Step 10.If your healthcare provider has told you to use Ciprofloxacin and Fluocinolone Acetonide Otic Solution in both ears, repeat Steps 2-9 for the other ear.Step 11.Safely throw away Ciprofloxacin and Fluocinolone Acetonide Otic Solution vials after use.This Instructions for Use has been approved by the Food and Drug Administration.Rev. 05/2019

* Please review the disclaimer below.