CIPROFLOXACIN HCL-FLUOCINOLONE (Generic for OTOVEL)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Otic Administration
-For otic use only.
-Warm the solution by holding the vial in the hand for 1 to 2 minutes. This is to avoid dizziness, which may result from the instillation of a cold solution into the ear canal.
-The patient should lie with the affected ear upward, and then instill the medication.
-Pump the tragus 4 times by pushing inward to facilitate penetration of the medication into the middle ear. Maintain this position for 1 minute. Repeat, if necessary, for the opposite ear.
-Discard vial after use.

Local adverse events associated with ciprofloxacin; fluocinolone otic solution among pediatric patients in clinical trials (n = 224) include otorrhea (5.4%), excessive granulation tissue (1.3%), ear infection (0.9%), ear pruritus (0.9%), tympanic membrane disorder (0.9%), auricular swelling (0.4%), and balance disorder (0.4%). Ear discomfort (otalgia), ear congestion, tinnitus, hypoacusis, and tympanostomy tube obstruction have been reported with ciprofloxacin; fluocinolone otic solution in post-marketing surveillance.

Serious and occasionally fatal hypersensitivity anaphylactoid reactions, including cardiovascular collapse, loss of consciousness, angioedema (including laryngeal edema, pharyngeal, or facial edema), airway obstruction, dyspnea, urticaria, and itching, have been reported in patients receiving systemic quinolones. Some reactions have occurred following the first dose. Discontinue ciprofloxacin; fluocinolone otic solution at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require immediate emergency treatment. Allergic reactions, flushing, and skin exfoliation have been reported with ciprofloxacin; fluocinolone otic solution in post-marketing surveillance.

Dysgeusia, paresthesias (tingling in ears), dizziness, and headache have been reported with ciprofloxacin; fluocinolone otic solution in post-marketing surveillance.

As with other antibiotic preparations, use of this product may result in overgrowth of nonsusceptible organisms, including fungi. Candidiasis has been reported with ciprofloxacin; fluocinolone otic solution in post-marketing surveillance. If the infection is not improved after one week of therapy, obtain cultures to guide further treatment. The widespread use of fluoroquinolone otic drops has resulted in the emergence of fluoroquinolone antimicrobial resistance; patients with recurrent ear discharge unresponsive to topical ciprofloxacin may need further evaluation. Culture and sensitivity testing may help guide management.

Ciprofloxacin; fluocinolone otic solution is contraindicated in patients with a hypersensitivity to fluocinolone acetonide or other corticosteroids (corticosteroid hypersensitivity), ciprofloxacin or other quinolones (quinolone hypersensitivity), or to any other components of the product.

Ciprofloxacin; fluocinolone otic solution is contraindicated in patients with a viral infection of the external ear canal, including varicella and herpes infection, or a fungal infection of the ear.

Discontinue ciprofloxacin; fluocinolone otic solution at the first appearance of a skin rash or any other sign of hypersensitivity. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, including cardiovascular collapse, loss of consciousness, angioedema (including laryngeal, pharyngeal, or facial edema), airway obstruction, dyspnea, urticaria, and itching, have been reported in patients receiving systemic quinolones. Some reactions have occurred after the first dose. Serious acute hypersensitivity reactions may require immediate emergency treatment.

As with other antibiotic preparations, use of ciprofloxacin; fluocinolone otic solution may result in overgrowth of nonsusceptible organisms including fungi. If the infection is not improved after one week of therapy, obtain cultures to guide further treatment. If otorrhea (ear discharge) is persistent after a full course of therapy, or if two or more episodes of otorrhea occur within 6 months, further evaluate to exclude an underlying condition such as cholesteatoma, foreign body, or a tumor.

Ciprofloxacin; fluocinolone otic solution is for otic use only; it is not for ophthalmic administration or parenteral administration.

Description: Ciprofloxacin; fluocinolone otic solution is indicated for the treatment of acute otitis media due to susceptible organisms in pediatric patients aged 6 months and older with tympanostomy tubes. 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. Fluocinolone is an anti-inflammatory corticosteroid and is included to aid in the resolution of the inflammatory response associated with the bacterial infection. Ciprofloxacin; fluocinolone otic solution was FDA-approved in April 2016.

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 with tympanostomy tubes (AOMT) due to susceptible organisms:
Otic dosage:
Infants 6 months and older and Children: Instill 0.25 mL (one single-dose vial) into the affected ear canal twice daily (approximately every 12 hours) for 7 days.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
1 to 5 months: Safety and efficacy have not been established.
6 months and older: 0.5 mL/ear/day.
-Children
0.5 mL/ear/day.
-Adolescents
Not indicated.

Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.

Patients with Renal Impairment Dosing
No dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Ciprofloxacin is a fluoroquinolone antibacterial; fluocinolone is a corticosteroid.
-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.
-Fluocinolone: 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; fluocinolone otic solution is administered topically to the ear.


-Special Populations
Otic Route
Systemic absorption of ciprofloxacin and fluocinolone after otic administration is minimal. In a pharmacokinetic analysis (n = 14), after 7 days of treatment with 0.25 mL of ciprofloxacin; fluocinolone otic solution twice daily, detectable plasma concentrations of ciprofloxacin (3 mcg/L) were observed in only 1 patient; however, this patient deviated from study protocol and also received treatment with ciprofloxacin 0.3% otic solution (comparator) in both ears. No detectable fluocinolone concentrations were observed.