This monograph discusses the use of the ciprofloxacin-hydrocortisone combination product for treatment of selected otic infections. Clinicians may wish to consult the individual monographs of Ciprofloxacin or Hydrocortisone for more information about each specific agent.
Ciprofloxacin hydrochloride and hydrocortisone are combined in a nonsterile otic suspension (Cipro(R) HC Otic) for the treatment of acute otitis externa in adult and pediatric patients over the age of 1 year due to susceptible strains of Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus. 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. Hydrocortisone is an anti-inflammatory corticosteroid and is included to aid in the resolution of the inflammatory response associated with the bacterial infection. Cipro(R) HC Otic was approved by the FDA on February 10, 1998.
General Administration Information
For storage information, see the specific product information in the How Supplied section.
Route-Specific Administration
Otic Administration
-The suspension should be warmed by holding the bottle in the hand for 1-2 minutes to avoid the dizziness which may result from instillation of a cold solution into the ear canal. Shake well immediately before using.
-The patient should lie with the affected ear upward during installation of the drops. The patient should continue to lie with the affected ear upward for 30-60 seconds to facilitate penetration of the drops into the ear. The dosage may be repeated, if necessary, for the opposite ear.
Adverse reactions to the ciprofloxacin; hydrocortisone otic suspension were evaluated during phase 3 clinical trials (n = 564). Headache (1.2%) and pruritus (0.4%) were adverse reactions considered to be at least remotely related to treatment. Other treatment-related adverse reactions included migraine, alopecia, cough, fungal dermatitis, hypoesthesia, paresthesias, rash (unspecified), and urticaria; each were reported in a single patient. Dizziness, ear canal erythema, ear congestion, and hypoacusis (hearing loss) have been reported in postmarketing surveillance. Theoretically, systemic adverse effects of the corticosteroid could occur with prolonged or excessive use; avoid use beyond recommended treatment durations.
Ciprofloxacin; hydrocortisone contains ciprofloxacin, a fluoroquinolone antibiotic. The widespread use of fluoroquinolone otic drops has resulted in the emergence of fluoroquinolone antimicrobial resistance; patients with recurrent otorrhea unresponsive to topical ciprofloxacin may need further evaluation. Culture and sensitivity testing may help guide management.
Ciprofloxacin; hydrocortisone otic (Cipro HC Otic) is for otic use only; it is not for ophthalmic administration or parenteral administration.
Ciprofloxacin; hydrocortisone otic is contraindicated in persons with a history of hypersensitivity to hydrocortisone (corticosteroid hypersensitivity), ciprofloxacin or any member of the quinolone class of antimicrobial agents (quinolone hypersensitivity). Use ciprofloxacin; hydrocortisone otic with caution in patients with latex hypersensitivity as the dropper cap contains natural rubber (latex) which may cause severe allergic reactions. Discontinue use at the first appearance of a skin rash or any other sign of hypersensitivity.
Ciprofloxacin; hydrocortisone otic should not be used if tympanic membrane perforation is present or suspected because the product is nonsterile. Use of this product is contraindicated in a viral infection of the external canal including varicella and active herpes infection (e.g., herpes simplex infection). In clinical trials, patients were required to be free of fungal infection or mycobacterial infection of the ears, active herpes infection (e.g., herpes simplex), overt viral infections of the ear (e.g., varicella), and other related disorders. As with other antibiotic preparations, use of this product may result in overgrowth of nonsusceptible organisms, including fungi. If the infection is not improved after 1 week of therapy, cultures should be obtained 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.
No adequate and well controlled studies have been conducted in pregnant women. Animal reproduction studies have not been conducted with ciprofloxacin; hydrocortisone otic. Use ciprofloxacin; hydrocortisone otic with caution during pregnancy.
Ciprofloxacin; hydrocortisone otic (Cipro HC Otic) suspension contains benzyl alcohol. Cipro HC Otic suspension should be used cautiously in those patients with a history of benzyl alcohol hypersensitivity.
Ciprofloxacin is excreted into breast milk following systemic administration. It is not known if topical otic administration could result in sufficient systemic absorption to produce detectable concentrations in human breast milk. Plasma concentrations were not measured after 3 drops of otic suspension administration because systemic exposure to ciprofloxacin is expected to be below the quantitation limit of the assay (0.05 mcg/mL). However because of the potential for serious adverse reactions in the breast-feeding infant, discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother.
Ciprofloxacin; hydrocortisone otic (Cipro HC Otic) is approved for use in children and infants aged 1 year and older. Safe and effective use in younger infants or neonates is not established.
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: Proteus mirabilis, Pseudomonas aeruginosa, Staphylococcus aureus (MSSA)
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 externa due to susceptible organisms:
Otic dosage (ciprofloxacin 0.2% and hydrocortisone 1% otic suspension):
Adults, Adolescents, and Children 1 year and older: 3 drops instilled into the affected ear(s) twice daily for 7 days.
Maximum Dosage Limits:
-Adults
6 drops/day to affected ear(s).
-Geriatric
6 drops/day to affected ear(s).
-Adolescents
6 drops/day to affected ear(s).
-Children
6 drops/day to affected ear(s).
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Ciprofloxacin; Hydrocortisone products.
-Ciprofloxacin: Ciprofloxacin is bactericidal via inhibition of DNA gyrase (topoisomerase II), an enzyme responsible for counteracting the excessive supercoiling of DNA during replication or transcription and topoisomerase IV, an enzyme that helps separate the daughter DNA molecules. In gram-negative bacteria, the primary target is the DNA gyrase A subunit, while the primary target in gram-positive bacteria is generally topoisomerase IV.
-Hydrocortisone: The antiinflammatory actions 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.
Cipro HC Otic is administered topically to the ear.
-Route-Specific Pharmacokinetics
Topical Route
Pharmacokinetics of ciprofloxacin and hydrocortisone following topical administration to the ear were not evaluated. The manufacturer reports that plasma concentrations of ciprofloxacin were not measured because the systemic exposure to ciprofloxacin is expected to be below the limit of quantitation of the assay (i.e., <= 0.05 mcg/mL). Similarly, the predicted Cmax of hydrocortisone is within the range of endogenous hydrocortisone concentration (i.e., 0-150 ng/mL), and therefore hydrocortisone plasma concentrations resulting from topical administration to the ear cannot be differentiated from endogenous cortisol.