CIPRODEX 0.3 % / 0.1 % Otic Suspension

Details

Generic Name: CIPROFLOXACIN AND DEXAMETHASONE

Brand Name: CIPRODEX

Substance Name(s):
CIPROFLOXACIN HYDROCHLORIDE
DEXAMETHASONE

OVERDOSAGE

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

DESCRIPTION

11 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:

CLINICAL STUDIES

14 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.

HOW SUPPLIED

16 /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 fill Storage: 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.

DOSAGE FORMS AND STRENGTHS

3 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. 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). (3)

MECHANISM OF ACTION

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.

INDICATIONS AND USAGE

1 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. CIPRODEX is a combination of ciprofloxacin, a fluoroquinolone antibacterial and dexamethasone, a corticosteroid, indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms in the specific 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. (1) Acute Otitis Externa in pediatric (age 6 months and older), adult and elderly patients due to Staphylococcus aureus and Pseudomonas aeruginosa. (1)

PEDIATRIC USE

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.

PREGNANCY

8.1 Pregnancy 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.

NUSRING MOTHERS

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.

WARNING AND CAUTIONS

5 WARNINGS AND PRECAUTIONS Hypersensitivity and anaphylaxis have been reported with systemic use of quinolones. Discontinue use if this occurs with use of CIPRODEX. (5.1) Prolonged use may result in overgrowth of non-susceptible bacteria and fungi. (5.2) 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.

INFORMATION FOR PATIENTS

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.

DOSAGE AND ADMINISTRATION

2 CIPRODEX is for topical use only, and not for ophthalmic use, or for injection. (2.1) Shake well immediately before use. (2.1) Instill four drops into the affected ear twice daily, for seven days. (2) 2.1 Important Administration Instructions CIPRODEX is for otic use only, and not for ophthalmic use, or for injection. Shake well immediately before use. 2.2 Dosage For the treatment of Acute Otitis Media in pediatric patients (age 6 months and older) with tympanostomy tubes The 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.