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.
1 Indications And Usage
- CIPRODEX is indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms in the specific conditions listed below:Acute Otitis Media in pediatric patients (age 6 months and older) with tympanostomy tubes due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa.Acute Otitis Externa in pediatric (age 6 months and older), adult and elderly patients due to Staphylococcus aureus and Pseudomonas aeruginosa.
2.1 Important Administration Instructions
- CIPRODEX is for otic use only, and not for ophthalmic use, or for injection.Shake well immediately before use.
- For the treatment of Acute Otitis Media in pediatric patients (age 6 months and older) with tympanostomy tubesThe recommended dosage regimen through tympanostomy tubes is as follows: Four drops (equivalent to 0.14 mL of CIPRODEX, (consisting of 0.42 mg of ciprofloxacin and 0.14 mg of dexamethasone)) instilled into the affected ear twice daily for seven days.The 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 a cold suspension.The patient should lie with the affected ear upward, and then the drops should be instilled.The tragus should then be pumped 5 times by pushing inward to facilitate penetration of the drops into the middle ear.This position should be maintained for 60 seconds. Repeat, if necessary, for the opposite ear. Discard unused portion after therapy is completed.For the treatment of Acute Otitis Externa (age 6 months and older)The recommended dosage regimen is as follows: Four drops (equivalent to 0.14 mL of CIPRODEX, (consisting of 0.42 mg ciprofloxacin and 0.14 mg dexamethasone)) instilled into the affected ear twice daily for seven days.The 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 a cold suspension.The patient should lie with the affected ear upward, and then the drops should be instilled.This position should be maintained for 60 seconds to facilitate penetration of the drops into the ear canal. Repeat, if necessary, for the opposite ear.Discard unused portion after therapy is completed.
3 Dosage Forms And Strengths
Otic Suspension: Each mL of CIPRODEX contains ciprofloxacin hydrochloride 0.3 % (equivalent to 3 mg ciprofloxacin base) and dexamethasone 0.1 % equivalent to 1 mg dexamethasone.
- CIPRODEX 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.
5.1 Hypersensitivity Reactions
CIPRODEX 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 CIPRODEX 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.
6 Adverse Reactions
- The following serious adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1)]Potential for Microbial Overgrowth with Prolonged Use [see Warnings and Precautions (5.2)]
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 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, a total of 937 patients were treated with CIPRODEX. This included 400 patients with acute otitis media with tympanostomy tubes and 537 patients with acute otitis externa. 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 a single patient: tympanostomy tube blockage; ear pruritus; tinnitus; oral moniliasis; crying; dizziness; and erythema.Acute Otitis Externa The 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 a 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 CIPRODEX. Because these reactions are reported voluntarily from a population of unknown size it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions include: auricular swelling, headache, hypersensitivity, otorrhea, skin exfoliation, rash erythematous, and vomiting.
Teratogenic Effects. Pregnancy Category C:No adequate and well controlled studies with CIPRODEX have been performed in pregnant women. Caution should be exercised when CIPRODEX is used by a pregnant woman. Animal reproduction studies have not been conducted with CIPRODEX.Reproduction studies with ciprofloxacin have been performed in rats and mice using oral doses of up to 100 mg/kg and IV doses up to 30 mg/kg and have revealed no evidence of harm to the fetus. In rabbits, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion, but no teratogenicity was observed at either dose. After intravenous administration of doses up to 20 mg/kg, no maternal toxicity was produced in the rabbit, and no embryotoxicity or teratogenicity was observed.Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals.
8.3 Nursing Mothers
Ciprofloxacin and corticosteroids, as a 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, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The safety and efficacy of CIPRODEX have been established in pediatric patients 6 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 4 to 12 years) treated with CIPRODEX and tested for audiometric parameters.
Due to the characteristics of this preparation, no toxic effects are to be expected with an otic overdose of this product.
CIPRODEX (ciprofloxacin 0.3% and dexamethasone 0.1%) Sterile Otic Suspension contains the quinolone antimicrobial, ciprofloxacin hydrochloride, combined with the corticosteroid, dexamethasone, in a sterile, preserved suspension for otic use. Each mL of CIPRODEX contains ciprofloxacin hydrochloride (equivalent to 3 mg ciprofloxacin base), 1 mg dexamethasone, and 0.1 mg benzalkonium chloride as a preservative. The inactive ingredients are boric acid, sodium chloride, hydroxyethyl cellulose, tyloxapol, acetic acid, sodium acetate, edetate disodium, and purified water. 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 empirical formula is C17H18FN3O3·HCl·H2O. The molecular weight is 385.82 and the structural formula is: Dexamethasone, 9-fluoro-11(beta),17,21-trihydroxy-16(alpha)-methylpregna-1,4-diene-3,20-dione, is a corticosteroid. The empirical formula is C22H29FO5. The molecular weight is 392.46 and the structural formula is:
12.1 Mechanism Of Action
Ciprofloxacin is a fluoroquinolone antibacterial [see Microbiology (12.4)].Dexamethasone, a 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.
Following a single bilateral 4-drop (total dose = 0.28 mL, 0.84 mg ciprofloxacin, 0.28 mg dexamethasone) topical otic dose of CIPRODEX to pediatric patients after tympanostomy tube insertion, measurable plasma concentrations of ciprofloxacin and dexamethasone were observed at 6 hours following administration in 2 of 9 patients and 5 of 9 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 2 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 2 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 acute otitis media with tympanostomy tubes).
- 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 antibacterial 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 BacteriaStaphylococcus aureusStreptococcus pneumoniaeGram-negative BacteriaHaemophilus influenzaeMoraxella catarrhalisPseudomonas aeruginosa
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 2 years, there was no evidence that ciprofloxacin had any carcinogenic or tumorigenic effects in these species. No long term studies of CIPRODEX have been performed to evaluate carcinogenic potential.Eight in vitro mutagenicity tests have been conducted with ciprofloxacin, and the test results are listed below: Salmonella/Microsome Test (Negative)E. coli DNA Repair Assay (Negative)Mouse Lymphoma Cell Forward Mutation Assay (Positive)Chinese Hamster 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)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 a patient treated with CIPRODEX 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 a 26-week study in male rats and resulted in changes to the testes, epididymis, sperm duct, prostate, seminal vessicle, Cowper's gland and accessory glands. The relevance of this study for short-term topical otic use is unknown.
13.2 Animal Toxicology And/Or Pharmacology
Guinea pigs dosed in the middle ear with CIPRODEX for one month exhibited no drug-related structural or functional changes of the cochlear hair cells and no lesions in the ossicles.
14 Clinical Studies
In a randomized, multicenter, controlled clinical trial, CIPRODEX dosed 2 times per day for 7 days demonstrated clinical cures in the per protocol analysis in 86% of Acute Otitis Media with Tympanostomy Tubes (AOMT) patients compared to 79% for ofloxacin solution, 0.3%, dosed 2 times per day for 10 days. Among culture positive patients, clinical cures were 90% for CIPRODEX compared to 79% for ofloxacin solution, 0.3%. Microbiological eradication rates for these patients in the same clinical trial were 91% for CIPRODEX compared to 82% for ofloxacin solution, 0.3%. In 2 randomized multicenter, controlled clinical trials, CIPRODEX dosed 2 times per day for 7 days demonstrated clinical cures in 87% and 94% of per protocol evaluable Acute Otitis Externa (AOE) patients, respectively, compared to 84% and 89%, respectively, for otic suspension containing neomycin 0.35%, polymyxin B 10,000 IU/mL, and hydrocortisone 1.0% (neo/poly/HC). Among culture positive patients clinical cures were 86% and 92% for CIPRODEX 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 CIPRODEX compared to 85% and 85%, respectively, for neo/poly/HC.
16 How Supplied/Storage And Handling
How Supplied:CIPRODEX (ciprofloxacin 0.3% and dexamethasone 0.1%) Sterile Otic Suspension is a white-to off-white suspension supplied as follows: 7.5 mL fill in a DROP-TAINER® system. The DROP-TAINER system consists of a natural polyethylene bottle and natural plug, with a white polypropylene closure. Tamper evidence is provided with a shrink band around the closure and neck area of the package. NDC 0065-8533-02, 7.5 mL fillStorage:Store at 20° - 25°C (68° - 77°F); excursions permitted to 15° - 30°C (59° - 86°F). [See USP Controlled Room Temperature]. Avoid freezing. Protect from light.
17 Patient Counseling Information
- Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use) For Otic Use Only Advise patients that CIPRODEX is for otic use only. This product is not approved for use in the eye.Administration Instructions Patients should be instructed to warm the bottle in their hand for one to two minutes prior to use and shake well immediately before using.Allergic Reactions Advise patients to discontinue use immediately and contact their physician, if rash or allergic reaction occurs.Avoid Contamination of the Product Advise patients to avoid contaminating the tip with material from the ear, fingers, or other sources.Duration of Use Advise patients that it is very important to use the ear drops for as long as their doctor has instructed, even if the symptoms improve.Protect from Light Advise patients to protect the product from light.Unused Product Advise patients to discard unused portion after therapy is completed.
Spl Patient Package Insert
PATIENT INFORMATION CIPRODEX (CI-PRO-DEX) (ciprofloxacin and dexamethasone) otic suspensionThis Patient Information has been approved by the U.S. Food and Drug Administration Revised: December 2015 What is CIPRODEX?CIPRODEX is a prescription medicine used in the ear only (otic use) that contains 2 medicines, a quinolone antibiotic medicine called ciprofloxacin and a corticosteroid medicine called dexamethasone. CIPRODEX is used in adults and children 6 months of age or older to treat certain types of infections caused by certain germs called bacteria. These bacterial infections include:●middle ear infection (known as acute otitis media) in people who have a tube in their eardrum known as a tympanostomy to prevent having too much fluid in the middle ear●outer ear canal infection (known as acute otitis externa)It is not known if CIPRODEX is safe and effective in children under 6 months of age. Who should not use CIPRODEX?Do not use CIPRODEX if you:●are allergic to ciprofloxin, quinolones, or any of the ingredients in CIPRODEX. See the end of this Patient Information leaflet for a complete list of ingredients in CIPRODEX.●have an outer ear canal infection caused by certain viruses including the herpes simplex virus●have an ear infection caused by a fungusWhat should I tell my doctor before using CIPRODEX?Before using CIPRODEX, tell your doctor about all of your medical conditions, including if you:●are pregnant or plan to become pregnant. It is not known if CIPRODEX will harm your unborn baby.●are breastfeeding or plan to breastfeed. CIPRODEX can pass into your breast milk and may harm your baby. You and your doctor should decide if you will use CIPRODEX 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 I use CIPRODEX?●Read the detailed Instructions for Use that come with CIPRODEX.●Use CIPRODEX exactly as your doctor tells you to.●CIPRODEX is for use in the ear only (otic use). Do not inject CIPRODEX or use CIPRODEX in the eye.●Apply 4 drops of CIPRODEX into the affected ear 2 times a day for 7 days.●Do not stop using CIPRODEX unless your doctor tells you to, even if your symptoms improve.If your symptoms do not improve after 7 days of treatment with CIPRODEX, call your doctor.●Call your doctor right away if: ○you have fluid that continues to drain from your ear (otorrhea) after you have finished your treatment with CIPRODEX ○you have fluid that drains from your ear 2 or more times within 6 months after you stop treatment with CIPRODEXWhat are the possible side effects of CIPRODEX?CIPRODEX may cause serious side effects, including:●allergic reactions. Stop using CIPRODEX and call your doctor if you have any of the following signs or symptoms of an allergic reaction: ○hives (urticaria) ○swelling of your face, lips, mouth, or tongue ○rash ○itching ○trouble breathing ○dizziness, fast heartbeat, or pounding in your chestThe most common side effects of CIPRODEX include:●ear discomfort●ear pain●ear itching (pruritus)These are not all the possible side effects of CIPRODEX. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should I store CIPRODEX? ●Store CIPRODEX at room temperature between 68°F to 77°F (20°C to 25°C).●Do not freeze CIPRODEX.●Keep CIPRODEX out of light.Keep CIPRODEX and all medicines out of the reach of children.General information about the safe and effective use of CIPRODEX.Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use CIPRODEX for a condition for which it was not prescribed. Do not give CIPRODEX 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 CIPRODEX that is written for health professionals.What are the ingredients in CIPRODEX?Active ingredients: ciprofloxacin hydrochloride, dexamethasone, and benzalkonium chloride as a preservativeInactive ingredients: boric acid, sodium chloride, hydroxyethyl cellulose, tyloxapol, acetic acid, sodium acetate, edetate disodium, and purified water. Sodium hydroxide or hydrochloric acid may be added for adjustment of pHDistributed by:Alcon Laboratories, Inc.Fort Worth, TX 76134 USA CIPRODEX® is a registered trademark of Bayer Intellectual Property GmbH, licensed to Alcon by Bayer Intellectual Property GmbH ©2003, 2004, 2008, 2009, 2012, 2015 Novartis U.S. Pat.: www.alconpatents.comFor more information, call 1-800-757-9785.Instructions for UseCIPRODEX (CI-PRO-DEX)(ciprofloxacin and dexamethasone)otic suspensionRead this Instructions for Use that comes with CIPRODEX 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 doctor about your medical condition or treatment. Important information about CIPRODEX: ●Use CIPRODEX exactly as your doctor tells you to use it. ●CIPRODEX is for use in the ear only (otic use). Do not inject CIPRODEX or use CIPRODEX in the eye. ●Shake CIPRODEX well before each use. ●Do not touch your ear, fingers or other surfaces with the tip of the CIPRODEX bottle. You may get bacteria on the tip of the bottle that can cause you to get another infection.How should I use CIPRODEX? Step 1. Wash your hands with soap and water. Figure A Step 2. Warm the bottle of CIPRODEX by rolling the bottle between your hands for 1 to 2 minutes (See Figure A). Shake the bottle of CIPRODEX well. Step 3. Remove the CIPRODEX cap. Put the cap in a clean and dry area. Do not let the tip of the bottle touch your ear, fingers or other surfaces. Figure B Step 4. Lie down on your side so that the affected ear faces upward (See Figure B). Figure C Step 5. Hold the bottle of CIPRODEX 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. Step 6. Gently squeeze the bottle and let 4 drops of CIPRODEX fall into the affected ear. If a drop misses your ear, follow the instructions in Step 5 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 CIPRODEX to enter the affected part of your ear. Step 8. If you use CIPRODEX to treat a middle ear infection and you have a tube in your eardrum known as a tympanostomy: ●Gently press the part of the ear known as the tragus (See Figure D) 5 times using a pumping motion (See Figure D). This will allow the drops of CIPRODEX to enter your middle ear. ●Remain on your side with the affected ear facing upward (See Figure B) for 1 minute. Figure D If you use CIPRODEX to treat an outer ear canal infection: ●Gently pull the outer ear lobe upward and backward (See Figure E). This will allow the drops of CIPRODEX to enter your ear canal. ●Remain on your side with the affected ear facing upward (See Figure B) for 1 minute. Figure E Step 9. If your doctor has told you to use CIPRODEX 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 CIPRODEX doses, there may be some CIPRODEX left in the bottle. Throw the bottle away. How should I store CIPRODEX? ●Store CIPRODEX at room temperature between 68⁰F to 77⁰F (20⁰C to 25⁰C). ●Do not freeze CIPRODEX. ●Keep CIPRODEX out of light. Keep CIPRODEX 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 CIPRODEX that is written for health professionals. This Instructions for Use has been approved by the U.S. Food and Drug Administration. Distributed by:Alcon Laboratories, Inc.Fort Worth, TX 76134 USA U.S. Pat.: www.alconpatents.com CIPRODEX® is a registered trademark of Bayer Intellectual Property GmbH, licensed to Alcon by Bayer Intellectual Property GmbH. ©2003, 2004, 2008, 2009, 2015 Novartis Revised: December 20159012314-1115
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