ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following serious adverse reactions are described elsewhere in the labeling:oHypersensitivity Reactions [see Warnings and Precautions (5.1)]oPotential for Microbial Overgrowth with Prolonged Use [see Warnings and Precautions (5.2)]. oHypersensitivity Reactions [see Warnings and Precautions (5.1)]. oPotential for Microbial Overgrowth with Prolonged Use [see Warnings and Precautions (5.2)]. Most common adverse reactions were ear discomfort (3%), ear pain (2.3%), and ear pruritus (1.5%). (6)To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc., at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.In Phases II and III clinical trials, total of 937 patients were treated with ciprofloxacin and dexamethasone otic suspension. This included 400 patients with acute otitis media with tympanostomy tubes (AOMT) and 537 patients with AOE. The reported adverse reactions are listed below:Acute Otitis Media in Pediatric Patients with Tympanostomy TubesThe following adverse reactions occurred in 0.5% or more of the patients with non-intact tympanic membranes.Adverse ReactionsIncidence (N 400)Ear discomfort3.0%Ear pain2.3%Ear precipitate (residue)0.5%Irritability0.5%Taste Perversion0.5%The following adverse reactions were each reported in single patient: tympanostomy tube blockage; ear pruritus; tinnitus; oral moniliasis; crying; dizziness; and erythema.Acute Otitis ExternaThe following adverse reactions occurred in 0.4% or more of the patients with intact tympanic membranes.Adverse ReactionsIncidence (N 537)Ear pruritus1.5%Ear debris0.6%Superimposed ear infection0.6%Ear congestion0.4%Ear pain0.4%Erythema 0.4%The following adverse reactions were each reported in single patient: ear discomfort; decreased hearing; and ear disorder (tingling).. 6.2 Postmarketing Experience. The following adverse reactions have been identified during post approval use of ciprofloxacin and dexamethasone otic suspension. Because these reactions are reported voluntarily from population of unknown size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure. These reactions include: auricular swelling, headache, hypersensitivity, otorrhea, skin exfoliation, rash erythematous, and vomiting.

ANIMAL PHARMACOLOGY & OR TOXICOLOGY SECTION.

13.2 Animal Toxicology and/or Pharmacology. Guinea pigs dosed in the middle ear with ciprofloxacin and dexamethasone otic suspension for one month exhibited no drug-related structural or functional changes of the cochlear hair cells and no lesions in the ossicles.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. 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 years, there was no evidence that ciprofloxacin had any carcinogenic or tumorigenic effects in these species. No long-term studies of ciprofloxacin and dexamethasone otic suspension have been performed to evaluate carcinogenic potential.Eight in vitro mutagenicity tests have been conducted with ciprofloxacin, and the test results are listed below: oSalmonella/Microsome Test (Negative)oE. coli DNA Repair Assay (Negative)oMouse Lymphoma Cell Forward Mutation Assay (Positive)oChinese Hamster V79 Cell HGPRT Test (Negative)oSyrian Hamster Embryo Cell Transformation Assay (Negative)oSaccharomyces cerevisiae Point Mutation Assay (Negative)oSaccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative)oRat Hepatocyte DNA Repair Assay (Positive)Thus, of the tests were positive, but results of the following in vivo test systems gave negative results:oRat Hepatocyte DNA Repair AssayoMicronucleus Test (Mice)oDominant Lethal Test (Mice)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 100 times the maximum recommended clinical dose of ototopical ciprofloxacin based upon body surface area, assuming total absorption of ciprofloxacin from the ear of patient treated with ciprofloxacin and dexamethasone otic suspension twice per day according to label directions.Long-term studies have not been performed to evaluate the carcinogenic potential of topical otic dexamethasone. Dexamethasone has been tested for in vitro and in vivo genotoxic potential and shown to be positive in the following assays: chromosomal aberrations, sister-chromatid exchange in human lymphocytes and micronuclei, and sister-chromatid exchanges in mouse bone marrow. However, the Ames/Salmonella assay, both with and without S9 mix, did not show any increase in His+ revertants. The effect of dexamethasone on fertility has not been investigated following topical otic application. However, the lowest toxic dose of dexamethasone identified following topical dermal application was 1.802 mg/kg in 26-week study in male rats and resulted in changes to the testes, epididymis, sperm duct, prostate, seminal vesicle, Cowpers gland, and accessory glands. The relevance of this study for short-term topical otic use is unknown.. oSalmonella/Microsome Test (Negative). oE. coli DNA Repair Assay (Negative). oMouse Lymphoma Cell Forward Mutation Assay (Positive). oChinese Hamster V79 Cell HGPRT Test (Negative). oSyrian Hamster Embryo Cell Transformation Assay (Negative). oSaccharomyces cerevisiae Point Mutation Assay (Negative). oSaccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative). oRat Hepatocyte DNA Repair Assay (Positive). oRat Hepatocyte DNA Repair Assay. oMicronucleus Test (Mice). oDominant Lethal Test (Mice).

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Ciprofloxacin is fluoroquinolone antibacterial [see Microbiology (12.4)]. Dexamethasone, corticosteroid, has been shown to suppress inflammation by inhibiting multiple inflammatory cytokines resulting in decreased edema, fibrin deposition, capillary leakage, and migration of inflammatory cells. 12.3 Pharmacokinetics. Following single bilateral 4-drop (total dose 0.28 mL, 0.84 mg ciprofloxacin, 0.28 mg dexamethasone) topical otic dose of ciprofloxacin and dexamethasone otic suspension to pediatric patients after tympanostomy tube insertion, measurable plasma concentrations of ciprofloxacin and dexamethasone were observed at hours following administration in of patients and of patients, respectively.Mean +- SD peak plasma concentrations of ciprofloxacin were 1.39 +- 0.880 ng/mL (n 9). Peak plasma concentrations ranged from 0.543 ng/mL to 3.45 ng/mL and were on average approximately 0.1% of peak plasma concentrations achieved with an oral dose of 250-mg. Peak plasma concentrations of ciprofloxacin were observed within 15 minutes to hours post dose application.Mean +- SD peak plasma concentrations of dexamethasone were 1.14 +- 1.54 ng/mL (n 9). Peak plasma concentrations ranged from 0.135 ng/mL to 5.10 ng/mL and were on average approximately 14% of peak concentrations reported in the literature following an oral 0.5-mg tablet dose. Peak plasma concentrations of dexamethasone were observed within 15 minutes to hours post dose application. Dexamethasone has been added to aid in the resolution of the inflammatory response accompanying bacterial infection (such as otorrhea in pediatric patients with AOMT).. 12.4 Microbiology. Mechanism of ActionThe bactericidal action of ciprofloxacin results from interference with the enzyme, DNA gyrase, which is needed for the synthesis of bacterial DNA.ResistanceCross-resistance has been observed between ciprofloxacin and other fluoroquinolones. There is generally no cross-resistance between ciprofloxacin and other classes of anti-bacterial agents, such as beta-lactams or aminoglycosides. Antimicrobial ActivityCiprofloxacin has been shown to be active against most isolates of the following microorganisms, both in vitro and clinically in otic infections [see Indications and Usage (1)].Aerobic BacteriaGram-positive BacteriaoStaphylococcus aureusoStreptococcus pneumoniaeGram-negative BacteriaoHaemophilus influenzaeoMoraxella catarrhalisoPseudomonas aeruginosa. oStaphylococcus aureus. oStreptococcus pneumoniae. oHaemophilus influenzae. oMoraxella catarrhalis. oPseudomonas aeruginosa.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. In randomized, multicenter, controlled clinical trial, ciprofloxacin and dexamethasone otic suspension dosed times per day for days demonstrated clinical cures in the per protocol analysis in 86% of AOMT patients compared to 79% for ofloxacin solution, 0.3%, dosed times per day for 10 days. Among culture positive patients, clinical cures were 90% for ciprofloxacin and dexamethasone otic suspension compared to 79% for ofloxacin solution, 0.3%. Microbiological eradication rates for these patients in the same clinical trial were 91% for ciprofloxacin and dexamethasone otic suspension compared to 82% for ofloxacin solution, 0.3%.In randomized multicenter, controlled clinical trials, ciprofloxacin and dexamethasone otic suspension dosed times per day for 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 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.

MICROBIOLOGY SECTION.

12.4 Microbiology. Mechanism of ActionThe bactericidal action of ciprofloxacin results from interference with the enzyme, DNA gyrase, which is needed for the synthesis of bacterial DNA.ResistanceCross-resistance has been observed between ciprofloxacin and other fluoroquinolones. There is generally no cross-resistance between ciprofloxacin and other classes of anti-bacterial agents, such as beta-lactams or aminoglycosides. Antimicrobial ActivityCiprofloxacin has been shown to be active against most isolates of the following microorganisms, both in vitro and clinically in otic infections [see Indications and Usage (1)].Aerobic BacteriaGram-positive BacteriaoStaphylococcus aureusoStreptococcus pneumoniaeGram-negative BacteriaoHaemophilus influenzaeoMoraxella catarrhalisoPseudomonas aeruginosa. oStaphylococcus aureus. oStreptococcus pneumoniae. oHaemophilus influenzae. oMoraxella catarrhalis. oPseudomonas aeruginosa.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. oCiprofloxacin and dexamethasone otic suspension is contraindicated in patients with history of hypersensitivity to ciprofloxacin, to other quinolones, or to any of the components in this medication.oUse of this product is contraindicated in viral infections of the external canal, including herpes simplex infections and fungal otic infections.. oCiprofloxacin and dexamethasone otic suspension is contraindicated in patients with history of hypersensitivity to ciprofloxacin, to other quinolones, or to any of the components in this medication.. oUse of this product is contraindicated in viral infections of the external canal, including herpes simplex infections and fungal otic infections.. oCiprofloxacin and dexamethasone otic suspension is contraindicated in patients with history of hypersensitivity to ciprofloxacin, to other quinolones, or to any of the components in this medication. (4)oUse of this product is contraindicated in viral infections of the external canal, including herpes simplex infections and fungal otic infections. (4). oCiprofloxacin and dexamethasone otic suspension is contraindicated in patients with history of hypersensitivity to ciprofloxacin, to other quinolones, or to any of the components in this medication. (4). oUse of this product is contraindicated in viral infections of the external canal, including herpes simplex infections and fungal otic infections. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension contains the quinolone antimicrobial, ciprofloxacin hydrochloride, combined with the corticosteroid, dexamethasone, in sterile, preserved suspension for otic use. Each mL of ciprofloxacin and dexamethasone otic suspension contains ciprofloxacin hydrochloride (equivalent to mg ciprofloxacin base), mg dexamethasone, and 0.1 mg benzalkonium chloride as preservative. The inactive ingredients are acetic acid, boric acid, edetate disodium, hydroxyethyl cellulose, purified water, sodium acetate, sodium chloride, and tyloxapol. Sodium hydroxide or hydrochloric acid may be added for adjustment of pH.Ciprofloxacin, 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 empirical formula is C17H18FN3O3.HCl.H2O. The molecular weight is 385.82 g/mol and the structural formula is: Dexamethasone, 9-fluoro-11(beta),17,21-trihydroxy-16(alpha)-methylpregna-1,4-diene-3,20-dione, is corticosteroid. The empirical formula is C22H29FO5. The molecular weight is 392.46 g/mol and the structural formula is:. figure1. figure2.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Ciprofloxacin and dexamethasone otic suspension is for otic use (ears) only, not for ophthalmic use, or for injection. (2.1)oShake well immediately before use. (2.1)oInstill four drops into the affected ear twice daily, for seven days. (2). oShake well immediately before use. (2.1). oInstill four drops into the affected ear twice daily, for seven days. (2). 2.1 Important Administration Instructions. oCiprofloxacin and dexamethasone otic suspension is for otic use (ears) only, and not for ophthalmic use, or for injection.oShake well immediately before use.. oCiprofloxacin and dexamethasone otic suspension is for otic use (ears) only, and not for ophthalmic use, or for injection.. oShake well immediately before use.. 2.2 Dosage. For the Treatment of Acute Otitis Media in Pediatric Patients (age months and older) with Tympanostomy TubesThe recommended dosage regimen through tympanostomy tubes is as follows: oFour drops [equivalent to 0.14 mL of ciprofloxacin and dexamethasone otic suspension, (consisting of 0.42 mg of ciprofloxacin and 0.14 mg of dexamethasone)] instilled into the affected ear twice daily for seven days.oThe suspension should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness, which may result from the instillation of cold suspension.oThe patient should lie with the affected ear upward, and then the drops should be instilled.oThe tragus should then be pumped times by pushing inward to facilitate penetration of the drops into the middle ear.oThis position should be maintained for 60 seconds. Repeat, if necessary, for the opposite ear.oDiscard unused portion after therapy is completed.For the Treatment of Acute Otitis Externa (age months and older)The recommended dosage regimen is as follows:oFour drops [equivalent to 0.14 mL of ciprofloxacin and dexamethasone otic suspension, (consisting of 0.42 mg ciprofloxacin and 0.14 mg dexamethasone)] instilled into the affected ear twice daily for seven days.oThe suspension should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness, which may result from the instillation of cold suspension.oThe patient should lie with the affected ear upward, and then the drops should be instilled.oThis position should be maintained for 60 seconds to facilitate penetration of the drops into the ear canal. Repeat, if necessary, for the opposite ear.oDiscard unused portion after therapy is completed.. oFour drops [equivalent to 0.14 mL of ciprofloxacin and dexamethasone otic suspension, (consisting of 0.42 mg of ciprofloxacin and 0.14 mg of dexamethasone)] instilled into the affected ear twice daily for seven days.. oThe suspension should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness, which may result from the instillation of cold suspension.. oThe patient should lie with the affected ear upward, and then the drops should be instilled.. oThe tragus should then be pumped times by pushing inward to facilitate penetration of the drops into the middle ear.. oThis position should be maintained for 60 seconds. Repeat, if necessary, for the opposite ear.. oDiscard unused portion after therapy is completed.. oFour drops [equivalent to 0.14 mL of ciprofloxacin and dexamethasone otic suspension, (consisting of 0.42 mg ciprofloxacin and 0.14 mg dexamethasone)] instilled into the affected ear twice daily for seven days.. oThe suspension should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness, which may result from the instillation of cold suspension.. oThe patient should lie with the affected ear upward, and then the drops should be instilled.. oThis position should be maintained for 60 seconds to facilitate penetration of the drops into the ear canal. Repeat, if necessary, for the opposite ear.. oDiscard unused portion after therapy is completed.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Otic Suspension: Each mL of ciprofloxacin and dexamethasone otic suspension contains ciprofloxacin hydrochloride 0.3% (equivalent to mg ciprofloxacin base) and dexamethasone 0.1% equivalent to mg dexamethasone.. Otic Suspension: Each mL of ciprofloxacin and dexamethasone otic suspension contains ciprofloxacin hydrochloride 0.3% (equivalent to mg ciprofloxacin base) and dexamethasone 0.1% (equivalent to mg dexamethasone). (3).

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. How Supplied:Ciprofloxacin 0.3% and dexamethasone 0.1% sterile otic suspension is white-to off-white suspension supplied as follows: 7.5 mL fill in DROP-TAINER(R) system. The DROP-TAINER system consists of natural polyethylene bottle and natural plug, with white polypropylene closure. Tamper evidence is provided with shrink band around the closure and neck area of the package.7.5 mL fill NDC 0781-6186-67Storage:Store at 20C to 25C (68F to 77F); excursions permitted to 15C to 30C (59F to 86F). See USP Controlled Room Temperature.Avoid freezing. Protect from light.

INDICATIONS & USAGE SECTION.

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 conditions listed below:oAcute Otitis Media (AOM) in pediatric patients (age months and older) with tympanostomy tubes due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa.oAcute Otitis Externa (AOE) in pediatric (age months and older), adult and elderly patients due to Staphylococcus aureus and Pseudomonas aeruginosa.. oAcute Otitis Media (AOM) in pediatric patients (age months and older) with tympanostomy tubes due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa.. oAcute Otitis Externa (AOE) in pediatric (age months and older), adult and elderly patients due to Staphylococcus aureus and Pseudomonas aeruginosa.. Ciprofloxacin and dexamethasone otic suspension is combination of ciprofloxacin, fluoroquinolone antibacterial and dexamethasone, corticosteroid, indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms in the specific conditions listed below:oAcute Otitis Media (AOM) in pediatric patients (age months and older) with tympanostomy tubes due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa. (1)oAcute Otitis Externa (AOE) in pediatric (age months and older), adult and elderly patients due to Staphylococcus aureus and Pseudomonas aeruginosa. (1). oAcute Otitis Media (AOM) in pediatric patients (age months and older) with tympanostomy tubes due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa. (1). oAcute Otitis Externa (AOE) in pediatric (age months and older), adult and elderly patients due to Staphylococcus aureus and Pseudomonas aeruginosa. (1).

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).For Otic Use OnlyAdvise patients that ciprofloxacin and dexamethasone otic suspension is for otic use (ears) only. This product must not be used in the eye [see Dosage and Administration (2.1) and Patient Information]. Administration InstructionsInstruct patients to warm the bottle in their hand for one to two minutes prior to use and shake well immediately before using [see Dosage and Administration (2.1, 2.2)].Allergic ReactionsAdvise patients to discontinue use immediately and contact their physician, if rash or allergic reaction occurs [see Warnings and Precautions (5.1)].Avoid Contamination of the ProductAdvise patients to avoid contaminating the tip with material from the ear, fingers, or other sources [see Instructions for Use].Duration of UseAdvise patients that it is very important to use the eardrops for as long as their doctor has instructed, even if the symptoms improve [see Patient Information].Protect From LightAdvise patients to protect the product from light [see How Supplied/Storage and Handling (16)].Unused ProductAdvise patients to discard unused portion after therapy is completed [see Dosage and Administration (2.2)].DROP-TAINER is trademark of Alcon. Distributed by: Sandoz Inc., Princeton, NJ 08540T2019-74. Distributed by: Sandoz Inc., Princeton, NJ 08540.

INSTRUCTIONS FOR USE SECTION.

INSTRUCTIONS FOR USECiprofloxacin and DexamethasoneOtic Suspension(sih-proe-FLOX-ah-sin) and (dex-ah-METH-ah-sone)Read this Instructions for Use that comes with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION before you start using it and each time you get refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.Important information about CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION:oUse CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION exactly as your doctor tells you to use it.oCIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is for use in the ear only (otic use). Do not inject CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION or use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION in the eye. oShake CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION well before each use.oDo not touch your ear, fingers, or other surfaces with the tip of the CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION bottle. You may get bacteria on the tip of the bottle that can cause you to get another infection.How should use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONStep 1. Wash your hands with soap and water.Step 2. Warm the bottle of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION by rolling the bottle between your hands for to minutes (See Figure A). Shake the bottle of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION well.Figure AStep 3. Remove the CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION cap. Put the cap in clean and dry area. Do not let the tip of the bottle touch your ear, fingers or other surfaces.Step 4. Lie down on your side so that the affected ear faces upward (See Figure B).Figure BStep 5. Hold the bottle of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION between your thumb and index finger (See Figure C). Place the tip of the bottle close to your ear. Be careful not to touch your fingers or ear with the tip of the bottle.Figure CStep 6. Gently squeeze the bottle and let drops of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION fall into the affected ear. If drop misses your ear, follow the instructions in Step again.Step 7. Stay on your side with the affected ear facing upward (See Figure B).It is important that you follow the instructions below for your specific ear infection, to allow CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to enter the affected part of your ear.Step 8.If you use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to treat middle ear infection, and you have tube in your eardrum known as tympanostomy: oGently press the part of the ear known as the tragus (See Figure D) times using pumping motion (See Figure D). This will allow the drops of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to enter your middle ear.oRemain on your side with the affected ear facing upward (See Figure B) for minute.Figure DIf you use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to treat an outer ear canal infection:oGently pull the outer ear lobe upward and backward (See Figure E). This will allow the drops of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to enter your ear canal.oRemain on your side with the affected ear facing upward (See Figure B) for minute.Figure EStep 9. If your doctor has told you to use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION in both ears, repeat steps 5-8 for your other ear.Step 10. Put the cap back on the bottle and close it tightly.Step 11. After you have used all of your CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION doses, there may be some CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION left in the bottle. Throw the bottle away.How should store CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONoStore CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION at room temperature between 68F to 77F (20C to 25C).oDo not freeze CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.oKeep CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION out of light.Keep CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION and all medicines out of the reach of children.If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for more information about CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION that is written for health professionals.Distributed by: Sandoz Inc., Princeton, NJ 08540This Instructions for Use has been approved by the U.S. Food and Drug Administration.Revised: February 2019T2019-76. oUse CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION exactly as your doctor tells you to use it.. oCIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is for use in the ear only (otic use). Do not inject CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION or use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION in the eye. oShake CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION well before each use.. oDo not touch your ear, fingers, or other surfaces with the tip of the CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION bottle. You may get bacteria on the tip of the bottle that can cause you to get another infection.. oGently press the part of the ear known as the tragus (See Figure D) times using pumping motion (See Figure D). This will allow the drops of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to enter your middle ear.. oRemain on your side with the affected ear facing upward (See Figure B) for minute.. oGently pull the outer ear lobe upward and backward (See Figure E). This will allow the drops of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to enter your ear canal.. oRemain on your side with the affected ear facing upward (See Figure B) for minute.. oStore CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION at room temperature between 68F to 77F (20C to 25C).. oDo not freeze CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.. oKeep CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION out of light.. wash. warm. sick. eardrop. tragus. up back.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Ciprofloxacin is fluoroquinolone antibacterial [see Microbiology (12.4)]. Dexamethasone, corticosteroid, has been shown to suppress inflammation by inhibiting multiple inflammatory cytokines resulting in decreased edema, fibrin deposition, capillary leakage, and migration of inflammatory cells.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. 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 years, there was no evidence that ciprofloxacin had any carcinogenic or tumorigenic effects in these species. No long-term studies of ciprofloxacin and dexamethasone otic suspension have been performed to evaluate carcinogenic potential.Eight in vitro mutagenicity tests have been conducted with ciprofloxacin, and the test results are listed below: oSalmonella/Microsome Test (Negative)oE. coli DNA Repair Assay (Negative)oMouse Lymphoma Cell Forward Mutation Assay (Positive)oChinese Hamster V79 Cell HGPRT Test (Negative)oSyrian Hamster Embryo Cell Transformation Assay (Negative)oSaccharomyces cerevisiae Point Mutation Assay (Negative)oSaccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative)oRat Hepatocyte DNA Repair Assay (Positive)Thus, of the tests were positive, but results of the following in vivo test systems gave negative results:oRat Hepatocyte DNA Repair AssayoMicronucleus Test (Mice)oDominant Lethal Test (Mice)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 100 times the maximum recommended clinical dose of ototopical ciprofloxacin based upon body surface area, assuming total absorption of ciprofloxacin from the ear of patient treated with ciprofloxacin and dexamethasone otic suspension twice per day according to label directions.Long-term studies have not been performed to evaluate the carcinogenic potential of topical otic dexamethasone. Dexamethasone has been tested for in vitro and in vivo genotoxic potential and shown to be positive in the following assays: chromosomal aberrations, sister-chromatid exchange in human lymphocytes and micronuclei, and sister-chromatid exchanges in mouse bone marrow. However, the Ames/Salmonella assay, both with and without S9 mix, did not show any increase in His+ revertants. The effect of dexamethasone on fertility has not been investigated following topical otic application. However, the lowest toxic dose of dexamethasone identified following topical dermal application was 1.802 mg/kg in 26-week study in male rats and resulted in changes to the testes, epididymis, sperm duct, prostate, seminal vesicle, Cowpers gland, and accessory glands. The relevance of this study for short-term topical otic use is unknown.. oSalmonella/Microsome Test (Negative). oE. coli DNA Repair Assay (Negative). oMouse Lymphoma Cell Forward Mutation Assay (Positive). oChinese Hamster V79 Cell HGPRT Test (Negative). oSyrian Hamster Embryo Cell Transformation Assay (Negative). oSaccharomyces cerevisiae Point Mutation Assay (Negative). oSaccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative). oRat Hepatocyte DNA Repair Assay (Positive). oRat Hepatocyte DNA Repair Assay. oMicronucleus Test (Mice). oDominant Lethal Test (Mice). 13.2 Animal Toxicology and/or Pharmacology. Guinea pigs dosed in the middle ear with ciprofloxacin and dexamethasone otic suspension for one month exhibited no drug-related structural or functional changes of the cochlear hair cells and no lesions in the ossicles.

NURSING MOTHERS SECTION.

8.3 Nursing Mothers. Ciprofloxacin and corticosteroids, as class, appear in milk following oral administration. Dexamethasone in breast milk could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical otic administration of ciprofloxacin or dexamethasone could result in sufficient systemic absorption to produce detectable quantities in human milk. Because of the potential for unwanted effects in nursing infants, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. NDC 0781-6186-67 Ciprofloxacin 0.3% and Dexamethasone 0.1%STERILE OTIC SUSPENSIONRx Only7.5 mLFOR USE INEARS ONLYSANDOZ carton.

PEDIATRIC USE SECTION.

8.4 Pediatric Use. The safety and efficacy of ciprofloxacin and dexamethasone otic suspension have been established in pediatric patients months and older (937 patients) in adequate and well-controlled clinical trials.No clinically relevant changes in hearing function were observed in 69 pediatric patients (age to 12 years) treated with ciprofloxacin and dexamethasone otic suspension and tested for audiometric parameters.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Following single bilateral 4-drop (total dose 0.28 mL, 0.84 mg ciprofloxacin, 0.28 mg dexamethasone) topical otic dose of ciprofloxacin and dexamethasone otic suspension to pediatric patients after tympanostomy tube insertion, measurable plasma concentrations of ciprofloxacin and dexamethasone were observed at hours following administration in of patients and of patients, respectively.Mean +- SD peak plasma concentrations of ciprofloxacin were 1.39 +- 0.880 ng/mL (n 9). Peak plasma concentrations ranged from 0.543 ng/mL to 3.45 ng/mL and were on average approximately 0.1% of peak plasma concentrations achieved with an oral dose of 250-mg. Peak plasma concentrations of ciprofloxacin were observed within 15 minutes to hours post dose application.Mean +- SD peak plasma concentrations of dexamethasone were 1.14 +- 1.54 ng/mL (n 9). Peak plasma concentrations ranged from 0.135 ng/mL to 5.10 ng/mL and were on average approximately 14% of peak concentrations reported in the literature following an oral 0.5-mg tablet dose. Peak plasma concentrations of dexamethasone were observed within 15 minutes to hours post dose application. Dexamethasone has been added to aid in the resolution of the inflammatory response accompanying bacterial infection (such as otorrhea in pediatric patients with AOMT).

PREGNANCY SECTION.

8.1 Pregnancy. Teratogenic Effects. Pregnancy Category C:No adequate and well controlled studies with ciprofloxacin and dexamethasone otic suspension have been performed in pregnant women. Caution should be exercised when ciprofloxacin and dexamethasone otic suspension is used by pregnant woman.Animal reproduction studies have not been conducted with ciprofloxacin and dexamethasone otic suspension.Reproduction studies with ciprofloxacin have been performed in rats and mice using oral doses of up to 100 mg/kg and intravenous (IV) doses up to 30 mg/kg, and have revealed no evidence of harm to the fetus. 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 IV 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.

RECENT MAJOR CHANGES SECTION.

Dosage and Administration, Important Administration Instructions (2.1)2/2019.

SPL PATIENT PACKAGE INSERT SECTION.

This Patient Information has been approved by the U.S. Food and Drug Administration.Revised: February 2019PATIENT INFORMATIONCiprofloxacin and DexamethasoneOtic Suspension(sih-proe-FLOX-ah-sin) and (dex-ah-METH-ah-sone) What is CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONCIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is prescription medicine used in the ear only (otic use) that contains medicines, quinolone antibiotic medicine called ciprofloxacin and corticosteroid medicine called dexamethasone. CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is used in adults and children months of age or older to treat certain types of infections caused by certain germs called bacteria. These bacterial infections include: omiddle ear infection (known as acute otitis media or AOM) in people who have tube in their eardrum known as tympanostomy to prevent having too much fluid in the middle earoouter ear canal infection (known as acute otitis externa or AOE) It is not known if CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is safe and effective in children under months of age. Who should not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION Do not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION if you:oare allergic to ciprofloxacin, quinolones, or any of the ingredients in CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION. See the end of this Patient Information leaflet for complete list of ingredients in CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.ohave an outer ear canal infection caused by certain viruses including the herpes simplex virusohave an ear infection caused by fungusWhat should tell my doctor before using CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONBefore using CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION, tell your doctor about all of your medical conditions, including if you:oare pregnant or plan to become pregnant. It is not known if CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION will harm your unborn baby.oare breastfeeding or plan to breastfeed. CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION can pass into your breast milk and may harm your baby. You and your doctor should decide if you will use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION or breastfeed. You should not do both. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How should use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONoRead the detailed Instructions for Use that come with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.oUse CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION exactly as your doctor tells you to.oCIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is for use in the ear only (otic use). Do not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION in the eye or inject CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.oApply drops of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION into the affected ear times day for days.oDo not stop using CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION unless your doctor tells you to, even if your symptoms improve. If your symptoms do not improve after days of treatment with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION, call your doctor. oCall your doctor right away if: oyou have fluid that continues to drain from your ear (otorrhea) after you have finished your treatment with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONoyou have fluid that drains from your ear or more times within months after you stop treatment with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONWhat are the possible side effects of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONCIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION may cause serious side effects, including:oallergic reactions. Stop using CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION and call your doctor if you have any of the following signs or symptoms of an allergic reaction: ohives (urticaria) otrouble breathing oswelling of your face, lips, mouth, or tongue odizziness, fast heartbeat, or pounding in your chest orash oitchingThe most common side effects of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION include:oear discomfortoear painoear itching (pruritus) These are not all the possible side effects of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should store CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONoStore CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION at room temperature between 68F to 77F (20C to 25C).oDo not freeze CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.oKeep CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION out of light.Keep CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION and all medicines out of the reach of children. General information about the safe and effective use of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION for condition for which it was not prescribed. Do not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION in the eye. Do not give CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION that is written for health professionals. What are the ingredients in CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION Active ingredients: ciprofloxacin hydrochloride, dexamethasone, and benzalkonium chloride as preservative Inactive ingredients: acetic acid, boric acid, edetate disodium, hydroxyethyl cellulose, purified water, sodium acetate, sodium chloride, and tyloxapol. Sodium hydroxide or hydrochloric acid may be added for adjustment of pH. Distributed by: Sandoz Inc., Princeton, NJ 08540 T2019-75. What is CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONCIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is prescription medicine used in the ear only (otic use) that contains medicines, quinolone antibiotic medicine called ciprofloxacin and corticosteroid medicine called dexamethasone. CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is used in adults and children months of age or older to treat certain types of infections caused by certain germs called bacteria. These bacterial infections include: omiddle ear infection (known as acute otitis media or AOM) in people who have tube in their eardrum known as tympanostomy to prevent having too much fluid in the middle ear. oouter ear canal infection (known as acute otitis externa or AOE). It is not known if CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is safe and effective in children under months of age. Who should not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION Do not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION if you:. oare allergic to ciprofloxacin, quinolones, or any of the ingredients in CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION. See the end of this Patient Information leaflet for complete list of ingredients in CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.. ohave an outer ear canal infection caused by certain viruses including the herpes simplex virus. ohave an ear infection caused by fungus. oare pregnant or plan to become pregnant. It is not known if CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION will harm your unborn baby.. oare breastfeeding or plan to breastfeed. CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION can pass into your breast milk and may harm your baby. You and your doctor should decide if you will use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION or breastfeed. You should not do both.. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. oRead the detailed Instructions for Use that come with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.. oUse CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION exactly as your doctor tells you to.. oCIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION is for use in the ear only (otic use). Do not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION in the eye or inject CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.. oApply drops of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION into the affected ear times day for days.. oDo not stop using CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION unless your doctor tells you to, even if your symptoms improve.. If your symptoms do not improve after days of treatment with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION, call your doctor. oCall your doctor right away if: oyou have fluid that continues to drain from your ear (otorrhea) after you have finished your treatment with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSIONoyou have fluid that drains from your ear or more times within months after you stop treatment with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION. oyou have fluid that continues to drain from your ear (otorrhea) after you have finished your treatment with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION. oyou have fluid that drains from your ear or more times within months after you stop treatment with CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION. oallergic reactions. Stop using CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION and call your doctor if you have any of the following signs or symptoms of an allergic reaction: ohives (urticaria). otrouble breathing. oswelling of your face, lips, mouth, or tongue. odizziness, fast heartbeat, or pounding in your chest. orash. oitching. oear discomfort. oear pain. oear itching (pruritus). These are not all the possible side effects of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. oStore CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION at room temperature between 68F to 77F (20C to 25C).. oDo not freeze CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.. oKeep CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION out of light.. General information about the safe and effective use of CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION for condition for which it was not prescribed. Do not use CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION in the eye. Do not give CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about CIPROFLOXACIN AND DEXAMETHASONE OTIC SUSPENSION that is written for health professionals. T2019-75.

SPL UNCLASSIFIED SECTION.

2.1 Important Administration Instructions. oCiprofloxacin and dexamethasone otic suspension is for otic use (ears) only, and not for ophthalmic use, or for injection.oShake well immediately before use.. oCiprofloxacin and dexamethasone otic suspension is for otic use (ears) only, and not for ophthalmic use, or for injection.. oShake well immediately before use.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Teratogenic Effects. Pregnancy Category C:No adequate and well controlled studies with ciprofloxacin and dexamethasone otic suspension have been performed in pregnant women. Caution should be exercised when ciprofloxacin and dexamethasone otic suspension is used by pregnant woman.Animal reproduction studies have not been conducted with ciprofloxacin and dexamethasone otic suspension.Reproduction studies with ciprofloxacin have been performed in rats and mice using oral doses of up to 100 mg/kg and intravenous (IV) doses up to 30 mg/kg, and have revealed no evidence of harm to the fetus. 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 IV 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.. 8.3 Nursing Mothers. Ciprofloxacin and corticosteroids, as class, appear in milk following oral administration. Dexamethasone in breast milk could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical otic administration of ciprofloxacin or dexamethasone could result in sufficient systemic absorption to produce detectable quantities in human milk. Because of the potential for unwanted effects in nursing infants, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.. 8.4 Pediatric Use. The safety and efficacy of ciprofloxacin and dexamethasone otic suspension have been established in pediatric patients months and older (937 patients) in adequate and well-controlled clinical trials.No clinically relevant changes in hearing function were observed in 69 pediatric patients (age to 12 years) treated with ciprofloxacin and dexamethasone otic suspension and tested for audiometric parameters.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. oHypersensitivity and anaphylaxis have been reported with systemic use of quinolones. Discontinue use if this occurs with use of ciprofloxacin and dexamethasone otic suspension. (5.1)oProlonged use may result in overgrowth of non-susceptible bacteria and fungi. (5.2). oHypersensitivity and anaphylaxis have been reported with systemic use of quinolones. Discontinue use if this occurs with use of ciprofloxacin and dexamethasone otic suspension. (5.1). oProlonged use may result in overgrowth of non-susceptible bacteria and fungi. (5.2). 5.1 Hypersensitivity Reactions. Ciprofloxacin and dexamethasone otic suspension should be discontinued at the first appearance of 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 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 tumor.

LACTATION SECTION.

8.2 Lactation Risk SummaryIt 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 or dexamethasone 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 mothers clinical need for ciprofloxacin and dexamethasone otic suspension and any potential adverse effects on the breast-fed child from ciprofloxacin and dexamethasone otic suspension.