General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Warm the suspension by holding the bottle in the hand for 1-2 minutes to avoid dizziness, which may result from instillation of a cold solution into the ear canal. Shake well immediately before using.
-Administer the drops without touching the tip of the bottle to the ear and with the patient lying down with the affected ear upward. For pediatric patients with acute otitis media, pump the tragus 5 times by pushing inward to facilitate penetration of the drops into the middle ear. For acute otitis externa, pull the earlobe up and back to facilitate penetration of the drops into the ear canal. All pediatric patients need to lie with the affected ear upward for 60 seconds after suspension administration. Administration may be repeated, if necessary, for the opposite ear.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving systemic quinolones sometimes after the first dose. Serious acute hypersensitivity reactions may require immediate emergency treatment. A child had an immediate type of hypersensitive reaction that was characterized by pruritus and multiple erythematous papules at the site of ciprofloxacin intravenous administration 5 minutes after drug infusion initiation. Headache, hypersensitivity, erythematous rash, skin exfoliation, and pruritus have been reported in post-marketing reports. Discontinue ciprofloxacin; dexamethasone at the first appearance of a skin rash (unspecified) or any other sign of hypersensitivity.
Ciprofloxacin; dexamethasone contains ciprofloxacin 0.3%, a fluoroquinolone antibiotic. No evidence of antimicrobial resistance to topical ciprofloxacin was noted among pediatric patients with tympanostomy tubes and acute otitis media. Specifically, susceptibility profiles of the treatment failures (34 of 800 patients) as compared with pretreatment profiles did not demonstrate changes in the minimum inhibitory concentration (MIC). Further, the 17 persistent isolates were genetically identical to the strains before ciprofloxacin receipt, pre-therapy MICs did not predict clinical failure, and the percentages of ciprofloxacin-resistant strains did not change significantly after therapy. Among pediatric patients with tympanostomy tubes, otorrhea, and acute otitis media not due to yeast, group A streptococci, or Pseudomonas aeruginosa, microbiologic eradication per intention-to-treat was noted in 74% of 31 ciprofloxacin; dexamethasone 4 drops twice daily for 7 days recipients and in 55% of 29 amoxicillin; clavulanic acid (90 mg/kg/day of amoxicillin) divided every 12 hours orally for 10 days recipients. In the per protocol analysis, microbiologic eradication was noted in 15 of 18 ciprofloxacin; dexamethasone recipients and in 13 of 22 amoxicillin; clavulanic acid recipients. Of the 3 treatment failures with ciprofloxacin; dexamethasone, none had new pathogens whereas 4 of 9 treatment failures with amoxicillin; clavulanic acid had new pathogens (polymicrobic cultures with either superinfectors or reinfectors). If the ear infection is not improved after one week of ciprofloxacin; dexamethasone, obtain cultures to guide further treatment. If otorrhea persists after a full course of therapy or if 2 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.
Systemic adverse events noted with the use of the ciprofloxacin; dexamethasone otic suspension in pediatric patients with tympanostomy tubes and acute otitis media include irritability (0.5%) and dysgeusia or taste perversion (0.5%). Oral candidiasis, crying, and dizziness were each reported in a single pediatric patient. Dizziness may result from the instillation of a cold suspension; warm the suspension by holding the bottle in the hand for 1 to 2 minutes before administration. Vomiting was noted in post-marketing reports.
Local adverse events associated with the ciprofloxacin; dexamethasone otic suspension among pediatric patients and adults include ear discomfort (3%), ear pain/otalgia (0.4 to 2.3%), ear precipitate (0.5%), ear pruritus (1.5%), ear debris (0.6%), ear congestion (0.4%), and erythema (0.4%). Tympanostomy tube blockage, decreased hearing, tinnitus, and ear disorder (tingling) were each reported in a single patient. No clinically relevant changes in hearing function were observed in 69 pediatric patients ages 4 to 12 years who received ciprofloxacin; dexamethasone otic suspension and were tested for audiometric parameters. Auricular swelling and otorrhea were noted in post-marketing reports.
Ciprofloxacin; dexamethasone otic suspension is contraindicated for use by persons with a history of hypersensitivity to ciprofloxacin, to other quinolones (quinolone hypersensitivity), or to any medication components. All of the fluoroquinolones have a similar core structure, so cross sensitivity is possible. The likely mechanism is IgE binding at the 7th position of the fluoroquinolone core structure. A child who had an immediate type of hypersensitive reaction at the site of ciprofloxacin intravenous administration 5 minutes after drug infusion initiation had itching and rashes within seconds of subsequent levofloxacin administration. Discontinue ciprofloxacin; dexamethasone at the first appearance of a skin rash or any other sign of hypersensitivity.
Ciprofloxacin; dexamethasone otic suspension is contraindicated for use by patients with a viral infection of the external canal including a herpes infection. As with other antibiotic preparations, use of ciprofloxacin; dexamethasone may result in overgrowth of nonsusceptible organisms including fungi. If the infection is not improved after one week of therapy, cultures should be obtained to guide further treatment. If otorrhea (ear discharge) persists after a full course of therapy or if >= 2 episodes of otorrhea occur within 6 months, further evaluation is recommended to exclude an underlying condition such as cholesteatoma, foreign body, or a tumor. In a clinical trial of ciprofloxacin; dexamethasone otic suspension, patients were required to be free of fungal infection or mycobacterial infection of the ears, active herpes simplex, vaccinia, varicella, or overt viral infections of the tympanic membrane, mastoiditis, or other suppurative noninfectious ear infections.
Ciprofloxacin; dexamethasone otic suspension is for otic use only; it is not for ophthalmic administration.
Description: Ciprofloxacin; dexamethasone otic suspension is indicated for acute otitis media (AOM) due to susceptible organisms in pediatric patients with tympanostomy tubes and for the topical treatment of acute otitis externa (AOE) in pediatric patients. Ciprofloxacin is a fluoroquinolone antibiotic with in vitro activity against a wide range of gram-positive and gram-negative microorganisms; topical use in the ear is not associated with ototoxicity. According to a consensus position statement, if possible and appropriate, use topical antibiotic preparations free of potential ototoxicity rather than preparations that have the potential for otologic injury if the middle ear or mastoid are open. Consider the use of non-ototoxic preparations in treating AOE when the tympanic membrane is perforated or its status is unknown, chronic suppurative otitis media, and tympanostomy tube otorrhea. Dexamethasone is an anti-inflammatory corticosteroid and is included to aid in the resolution of the inflammatory response associated with the bacterial infection. In a study, use of the combination as compared with ciprofloxacin otic suspension alone led to otorrhea resolution 1.1 days earlier among pediatric patients with tympanostomy tubes and AOM. Among patients who were clinically and microbiologically evaluable, microbiologic eradication was noted in 90.7% of 75 ciprofloxacin; dexamethasone recipients and in 79.7% of 64 in the topical ciprofloxacin monotherapy group. In another study, more children with patent tympanostomy tubes, a clinical diagnosis of AOM with otorrhea, and granulation tissue had resolution of granulation tissue with ciprofloxacin; dexamethasone than with topical ofloxacin. For example, on day 3 of treatment, 47% of 48 ciprofloxacin; dexamethasone recipients had an absence of granulation tissue as compared with 29% of 41 topical ofloxacin recipients. After treatment (day 18), 91% of the ciprofloxacin; dexamethasone recipients had an absence of granulation tissue as compared with 73% of the topical ofloxacin recipients. Topical antimicrobials with or without topical corticosteroids are the mainstay of treatment for uncomplicated AOE; the addition of a topical corticosteroid yields more rapid improvement in symptoms such as pain, canal edema, and erythema. An expert consensus panel concluded that in the absence of systemic infection or serious underlying disease, topical antibiotics alone constitute first-line treatment for most patients with chronic suppurative otitis media, tympanostomy tube otorrhea, and otitis externa; no evidence was found that systemic antibiotics alone or in combination with topical preparations improve treatment outcomes as compared with topical antibiotics alone. In a comparative study of pediatric patients with AOM, otorrhea, and tympanostomy tubes, receipt of topical ciprofloxacin; dexamethasone as compared with oral amoxicillin; clavulanic acid led to a significantly shorter median time to otorrhea cessation (4 vs. 7 days, respectively) and significantly more clinical cures on day 18 (85% vs. 59%, respectively). Ciprofloxacin;dexamethasone otic suspension is FDA approved for use in pediatric patients as young as 6 months of age.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus (MSSA), Streptococcus pneumoniae
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of acute otitis media due to susceptible organisms in pediatric patients with tympanostomy tubes:
Infants >= 6 months, Children, and Adolescents: 4 drops/dose instilled into the affected ear(s) twice daily for 7 days.
For the treatment of acute otitis externa due to susceptible organisms:
Infants >= 6 months, Children, and Adolescents: 4 drops/dose instilled into the affected ear(s) twice daily for 7 days. In a study that included both pediatric patients and adults with intact tympanic membranes, higher clinical cure rates of acute otitis externa were noted among ciprofloxacin; dexamethasone recipients (90.9%) as compared with hydrocortisone; neomycin; polymyxin B recipients (83.9%).
Maximum Dosage Limits:
Safety and efficacy have not been established.
< 6 months: Safety and efficacy have not been established.
>= 6 months: 8 drops/ear/day.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
Monograph content under development
Mechanism of Action: -Ciprofloxacin: The bactericidal action of ciprofloxacin results from interference with the bacterial enzyme DNA gyrase (topoisomerase II), which is needed for the synthesis of bacterial DNA. Specifically, quinolones are thought to inhibit resealing of DNA double strand by A subunits, which leaves single-strand DNA exposed to exonucleolytic degradation. At clinically achievable concentrations, ciprofloxacin is not thought to inhibit human topoisomerase II.
-Dexamethasone: Dexamethasone is a potent glucocorticoid. Glucocorticoids prevent or suppress inflammation and immune responses when administered at pharmacological doses. At the molecular level, unbound glucocorticoids readily cross cell membranes and bind with high affinity to specific cytoplasmic receptors. This binding induces a response by modifying transcription and, ultimately, protein synthesis to achieve the steroid's intended action. Such actions can include inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, and suppression of humoral immune responses. Some of the net effects include reduction in edema or scar tissue and a general suppression in immune response. The anti-inflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, collectively called lipocortins. Lipocortins, in turn, control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of the precursor molecule arachidonic acid.
Pharmacokinetics: Ciprofloxacin; dexamethasone otic suspension is administered topically to the ear. The half-life of ciprofloxacin was 3 +/- 1.2 hours and of dexamethasone was 3.9 +/- 2.9 hours after administration of 4 drops of ciprofloxacin; dexamethasone through tympanostomy tubes in each ear (8 drops/child) to pediatric patients 1-14 years of age.
-Ciprofloxacin: After tympanostomy tube insertion and 6 hours after administration of 4 drops to each ear, measurable plasma concentrations of ciprofloxacin were observed in 2 of 9 pediatric patients. Peak plasma ciprofloxacin concentrations were noted within 2 hours of administration, the mean was 1.39 +/- 0.880 ng/ml (range, 0.543-3.45 ng/ml), and were, on average, approximately 0.1% of peak plasma concentrations achieved with an oral dose of 250 mg. Serum drug concentrations were measured 6 hours after administration of 4 drops of ciprofloxacin; dexamethasone through tympanostomy tubes in each ear (8 drops/child) to pediatric patients 1-14 years of age: 4 of 25 children had ciprofloxacin concentrations >= 0.5 ng/ml. In 10 adults, no measurable ciprofloxacin (lowest detectable limit of 0.5 mcg/ml) in the labyrinthine fluid, cerebrospinal fluid, or serum was noted after installation of 0.5 ml of 0.3% ciprofloxacin solution into the middle ear. The time interval between the ciprofloxacin application to the round window membrane and sampling of labyrinthine fluid and plasma ranged from 9 to 120 minutes. The data suggest a lack of absorption through the round window membrane.
-Dexamethasone: After tympanostomy tube insertion and 6 hours after administration of 4 drops to each ear, measurable plasma concentrations of dexamethasone were noted in 5 of 9 pediatric patients. Peak plasma dexamethasone concentrations were noted within 2 hours of administration, the mean was 1.14 +/- 1.54 ng/ml (range, 0.135-5.1 ng/ml), and were on average approximately 14% of peak plasma concentrations reported in the literature after an oral 0.5 mg tablet dose. Serum drug concentrations were measured 6 hours after administration of 4 drops of ciprofloxacin; dexamethasone through tympanostomy tubes in each ear (8 drops/child) to pediatric patients 1-14 years of age: 14 of 24 pediatric patients had dexamethasone concentrations >= 0.05 ng/ml.