Ciprofloxacin is a fluoroquinolone anti-infective agent.1, 5, 8, 55, 119, 125, 126, 127, 133, 134
Bacterial Ophthalmic Infections
Ciprofloxacin 0.3% ophthalmic solution is used for the topical treatment of bacterial conjunctivitis caused by susceptible Staphylococcus aureus , S. epidermidis, Streptococcus pneumoniae , or Haemophilus influenzae .1, 134
Ciprofloxacin 0.3% ophthalmic ointment is used for the topical treatment of bacterial conjunctivitis caused by susceptible S. aureus , S. epidermidis , S. pneumoniae , viridans streptococci, or H. influenzae .119
Although mild, acute bacterial conjunctivitis often resolves spontaneously without anti-infective treatment,135, 136, 137, 141 topical ophthalmic anti-infectives may shorten the time to resolution and reduce severity and risk of complications.135, 136, 137, 141 Treatment of acute bacterial conjunctivitis generally is empiric and use of a broad-spectrum topical ophthalmic antibacterial usually is recommended;135, 136, 141 however, indiscriminate use of topical anti-infectives should be avoided.135, 141 In vitro staining and/or cultures of conjunctival material may be indicated in the management of recurrent, severe, or chronic purulent conjunctivitis or when acute conjunctivitis does not respond to initial empiric topical treatment.135, 136, 141
Results of a placebo-controlled and a comparative study indicate that ciprofloxacin 0.3% ophthalmic solution is more effective than placebo (e.g., vehicle) and as effective as tobramycin 0.3% ophthalmic solution in patients with acute bacterial conjunctivitis caused by various gram-positive and -negative bacteria.104 In these studies, topical application of ciprofloxacin 0.3% ophthalmic solution to the eye for 3-7 days was effective in reducing or eradicating all conjunctival pathogens in approximately 70-95% of patients with acute bacterial conjunctivitis1, 3, 104, 111, 134 but produced clinical cures less frequently.1, 3
In clinical studies, treatment with ciprofloxacin 0.3% ophthalmic ointment was associated with clinical cure in approximately 75% of patients with bacterial conjunctivitis and positive conjunctival cultures, and the presumed pathogens were eradicated by day 7 in approximately 80% of patients.119
Ciprofloxacin 0.3% ophthalmic solution is used for the topical treatment of keratitis (corneal ulcers) caused by susceptible S. aureus , S. epidermidis , S. pneumoniae , viridans streptococci, Serratia marcescens , or Pseudomonas aeruginosa .1, 24, 25, 26, 27, 101, 102, 103, 112, 134
Ciprofloxacin ophthalmic solution also has been used with variable success with other systemic and/or ophthalmic anti-infectives in the management of keratitis caused by nontuberculous mycobacteria† (e.g., Mycobacterium gordonae , M. fortuitum , M. chelonae ).28, 29, 121 Treatment with more than one anti-infective agent may be needed for the treatment of keratitis caused by such organisms.138
Because many forms of bacterial keratitis are associated with subsequent loss of vision as the result of corneal scarring or topographic irregularities and because untreated or severe bacterial keratitis may result in perforation of the cornea with the potential for endophthalmitis and possible loss of the eye, optimal management involves rapid evaluation and diagnosis, timely initiation of treatment, and appropriate follow-up.138 Treatment of community-acquired bacterial keratitis generally is empiric and use of a broad-spectrum topical ophthalmic antibacterial usually is recommended.138 Subconjunctival therapy with an appropriate anti-infective may be necessary if scleral spread or perforation is imminent.138 In vitro staining and/or cultures are indicated in the management of keratitis involving corneal infiltrates that are central, large, and extending to the middle to deep stroma or when keratitis is chronic or unresponsive to treatment with a broad-spectrum topical anti-infective.138
In a multicenter study in patients with corneal ulcers and positive conjunctival cultures, treatment with ciprofloxacin 0.3% ophthalmic solution in the recommended dosage resulted in clinical cure (i.e., complete reepithelialization, no evidence of bacterial infection, absence of symptoms) in 76% of patients; complete reepithelialization with no evidence of bacterial infection occurred in 92% of patients.1, 25, 134 In this study, success of ciprofloxacin therapy did not depend on the severity (initial size) of the corneal ulcer, and such therapy also was effective in most patients with bacterial keratitis that did not respond to treatment with other ophthalmic anti-infectives.25
Ciprofloxacin 0.2% otic solution is used for the topical treatment of acute bacterial otitis externa caused by susceptible S. aureus or Ps. aeruginosa .133
The fixed-combination ciprofloxacin and dexamethasone otic suspension (ciprofloxacin 0.3% and dexamethasone 0.1%) is used for the topical treatment of acute otitis externa caused by susceptible S. aureus or Ps. aeruginosa .125
The fixed-combination ciprofloxacin and hydrocortisone otic suspension (ciprofloxacin 0.2% and hydrocortisone 1%) is used for the topical treatment of acute bacterial otitis externa caused by susceptible S. aureus , Proteus mirabilis , or Ps. aeruginosa .120 Unlike other otic preparations containing ciprofloxacin,133, 125, 126 the commercially available fixed-combination ciprofloxacin and hydrocortisone otic suspension is nonsterile and should not be used if the tympanic membrane is known or suspected to be perforated.120
Diffuse, uncomplicated acute otitis externa in otherwise healthy patients usually should be treated initially with topical therapy (e.g., otic anti-infective or antiseptic with or without an otic corticosteroid).139, 143 Topical therapy should be supplemented with systemic anti-infective therapy if the patient has a medical condition that could impair host defenses (e.g., diabetes mellitus, human immunodeficiency virus [HIV] infection) or if the infection has spread into the pinna or skin of the neck or face, or into deeper tissues such as occurs with malignant otitis externa.139 Malignant otitis externa is an invasive, potentially life-threatening infection, especially in immunocompromised patients, and requires prompt diagnosis and long-term treatment with systemic anti-infectives.123, 124, 139
In a randomized, multicenter, evaluator-blinded study in patients with acute otitis externa, patients received either ciprofloxacin 0.2% otic solution (twice daily for 7 days) or a fixed-combination otic solution containing neomycin, polymyxin B sulfates, and hydrocortisone (3 times daily for 7 days).133 In the per-protocol population, clinical cure was achieved at the end of the 7-day regimen in 70% of those treated with the ciprofloxacin otic solution versus 60% of those who received the fixed-combination preparation.133
Safety and efficacy of the fixed-combination otic suspension containing ciprofloxacin and dexamethasone (ciprofloxacin 0.3% and dexamethasone 0.1%) for the treatment of acute otitis externa were evaluated in 2 randomized, multicenter, controlled trials.125 The clinical cure rate in the per-protocol population in trial 1 or 2 was 87 or 94%, respectively, in patients treated with the fixed-combination ciprofloxacin and dexamethasone otic suspension compared with 84 or 89%, respectively, in those treated with a fixed-combination otic suspension containing neomycin, polymyxin B, and hydrocortisone.125 Among culture-positive patients in these 2 studies, clinical cures were obtained in 86 or 92% of patients treated with the fixed-combination ciprofloxacin and dexamethasone otic suspension compared with 84 or 89% of patients treated with the fixed-combination neomycin, polymyxin B, and hydrocortisone otic suspension;125 microbiologic eradication rates were 86 or 92% compared with 85 or 85%, respectively.125
The fixed-combination ciprofloxacin and dexamethasone otic suspension (ciprofloxacin 0.3% and dexamethasone 0.1%) is used topically for the treatment of acute otitis media caused by susceptible S. aureus , S. pneumoniae , H. influenzae , Moraxella catarrhalis , or Ps. aeruginosa in patients with tympanostomy tubes.125
The fixed-combination ciprofloxacin and fluocinolone acetonide otic solution (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%) is used topically for the treatment of acute otitis media caused by susceptible S. aureus , S. pneumoniae , H. influenzae , M. catarrhalis , or Ps. aeruginosa in patients with tympanostomy tubes.126
In a randomized, multicenter, controlled trial in patients with tympanostomy tubes and acute otitis media, the clinical cure rate in the per-protocol population was 86% in patients treated with the fixed-combination otic suspension containing ciprofloxacin and dexamethasone (ciprofloxacin 0.3% and dexamethasone 0.1%) twice daily for 7 days compared with 79% in patients treated with ofloxacin 0.3% otic solution twice daily for 10 days.125 Among culture-positive patients, clinical cures were achieved in 90% of those treated with the fixed-combination ciprofloxacin and dexamethasone otic suspension compared with 79% of those treated with ofloxacin 0.3% otic solution;125 microbiologic eradication rates were 91 and 82%, respectively.125
Safety and efficacy of the fixed-combination otic solution containing ciprofloxacin and fluocinolone acetonide (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%) were evaluated in 2 multicenter, randomized, double-blind, active-controlled, phase 3 trials that included 662 pediatric patients 6 months to 12 years of age with acute otitis media with tympanostomy tubes.126 In both studies, patients were randomized to receive the fixed-combination otic solution, single-entity ciprofloxacin otic solution, or single-entity fluocinolone acetonide otic solution.126 In trial 1 or 2, cessation of otorrhea by day 22 was reported in 79 or 78% of patients, respectively, treated with the fixed-combination otic preparation of ciprofloxacin and fluocinolone acetonide compared with 67 or 69%, respectively, of patients treated with the otic preparation containing ciprofloxacin alone and 48 or 44%, respectively, of patients treated with the otic preparation containing the corticosteroid alone.126 The median time to cessation of otorrhea was 4 or 5 days in those treated with the fixed combination of ciprofloxacin and fluocinolone acetonide in study 1 or 2, respectively, compared with 8 or 7 days in those treated with the otic preparation containing ciprofloxacin alone.126
Ciprofloxacin 6% otic suspension is administered intratympanically for the treatment of bilateral otitis media with effusion in pediatric patients undergoing tympanostomy tube placement.127
Safety and efficacy of an intraoperative dose of ciprofloxacin 6% otic suspension (0.1 mL) for the treatment of bilateral otitis media with effusion in pediatric patients undergoing myringotomy with tympanostomy tube placement were evaluated in 2 randomized, multicenter, controlled, phase 3 clinical trials that included 532 patients.127 Enrolled patients had a median age of 1.5 years;127, 140 62% were 6 months through 2 years of age and 38% were older than 2 years of age.127 The efficacy end point for both trials was the cumulative proportion of study treatment failures through day 15, defined as the occurrence of any of the following: otorrhea as determined by a blinded assessor on or after 3 days postsurgery, use of otic or systemic antibacterials for any reason any time postsurgery, or patients who missed visits or were lost to follow-up.127, 140 In trial 1 or 2, treatment failure occurred in 25 or 21% of patients, respectively, who received intratympanic ciprofloxacin 6% otic suspension compared with 45 or 46% of patients, respectively, who received sham treatment (tympanostomy tube placement only).127, 140 There was no evidence of impaired hearing function, middle ear function, or tube patency at day 29 after intratympanic administration of ciprofloxacin 6% otic suspension.127, 140
For systemic uses of ciprofloxacin, see Ciprofloxacin 8:12.18.
Ciprofloxacin is applied topically to the eye as a 0.3% ophthalmic solution1, 134 or 0.3% ophthalmic ointment.119
Ciprofloxacin ophthalmic solution and ointment are for topical ophthalmic use only and should not be injected into the eye.1, 119, 134
Care should be taken to avoid contaminating the applicator tip with material from any source.1, 119, 134
Ciprofloxacin is instilled topically into the ear canal as a 0.2% otic solution.133
Ciprofloxacin in fixed combination with a corticosteroid (i.e., dexamethasone, fluocinolone acetonide, or hydrocortisone) is instilled topically into the ear canal as an otic solution or suspension.120, 125, 126
Ciprofloxacin otic solution and fixed-combination otic solutions or suspensions containing ciprofloxacin and a corticosteroid are for topical otic use only ;120, 125, 126, 133 these preparations are not for ophthalmic use, injection, or inhalation.120, 125, 126, 133
To avoid dizziness that may result from instilling a cold preparation into the ear canal, the container of otic solution or suspension should be warmed in the hands for 1-2 minutes before use.120, 125, 126, 133
Otic suspensions containing ciprofloxacin should be shaken well prior to use.120, 125
The patient should lie with the affected ear upward.120, 125, 126, 133 The appropriate amount of otic solution or suspension should be instilled into the ear;120, 125, 126, 133 this position should be maintained for at least 1 minute to facilitate penetration into the ear canal.120, 125, 126, 133 When treating acute otitis media, the tragus of the ear should be pumped 4 or 5 times by pushing inward to facilitate penetration of the solution into the middle ear.125, 126 The procedure should be repeated for the opposite ear if necessary.120, 125, 126, 133
Care should be taken to avoid contaminating the applicator tip with material from the ear, fingers, or other source.120, 125
Otic Administration (Intratympanic)
Ciprofloxacin is administered intratympanically as a 6% otic suspension.127
Ciprofloxacin 6% otic suspension is for intratympanic administration only .127
The manufacturer's instructions should be consulted for specific information regarding preparation and intratympanic administration of ciprofloxacin 6% otic suspension.127
Ciprofloxacin 6% otic suspension is thermosensitive and exists as a liquid at room temperature or lower, but thickens (gels) when warmed.127, 142 During preparation, the suspension must be kept cold and should be placed back into a refrigerator if it thickens.127 (See Chemistry and Stability: Stability.)
Each vial of ciprofloxacin 6% otic suspension is for single-patient use only and contains a volume sufficient to provide 2 doses (1 dose in each ear administered using a different syringe for each ear).127 Only the syringes and needles provided by the manufacturer should be used to administer the otic suspension.127 After the syringes are prepared, they should be kept on their side either at room temperature or in the refrigerator and must be discarded if not used within 3 hours.127
Middle ear effusions should be suctioned prior to intratympanic administration of ciprofloxacin 6% otic suspension.127
Ciprofloxacin is commercially available for topical ophthalmic administration1, 119, 134 and for topical otic administration120, 125, 126, 133 as ciprofloxacin hydrochloride; dosage is expressed in terms of ciprofloxacin.1, 119, 120, 125, 126, 133, 134
Bacterial Ophthalmic Infections
For the topical treatment of bacterial conjunctivitis in adults and pediatric patients, 1 or 2 drops of ciprofloxacin 0.3% ophthalmic solution should be instilled in the conjunctival sac of the affected eye(s) every 2 hours while awake (up to 8 times daily) on days 1 and 2, then 1 or 2 drops of the ophthalmic solution should be instilled every 4 hours while awake on days 3 through 7.1, 134
When ciprofloxacin 0.3% ophthalmic ointment is used for the topical treatment of bacterial conjunctivitis in adults and children 2 years of age and older, a ribbon of the ophthalmic ointment approximately 1.27 cm (½ inch) in length should be placed in the lower conjunctival sac of the infected eye(s) 3 times daily on days 1 and 2, then 2 times daily on days 3 through 7.119
The usual duration of topical anti-infective treatment for bacterial conjunctivitis is 5-10 days;135, 136, 141 some experts state that 5-7 days of such treatment usually is adequate for mild bacterial conjunctivitis.135
For the topical treatment of bacterial keratitis (corneal ulcers) in adults and pediatric patients, 2 drops of ciprofloxacin 0.3% ophthalmic solution should be instilled in the affected eye(s) every 15 minutes for the first 6 hours, followed by 2 drops in the affected eye(s) every 30 minutes for the remainder of the first day of treatment.1, 134 On day 2 of treatment, 2 drops of the solution should be instilled in the affected eye(s) every hour; on days 3 through 14, 2 drops should be instilled every 4 hours.1, 134
The manufacturers state that treatment may be continued for longer than 14 days if corneal reepithelialization has not occurred;1, 134 in clinical trials in patients with bacterial keratitis, the duration of topical ciprofloxacin treatment averaged about 3 weeks.3 Some experts state that the initial regimen should be reevaluated and modified if there is no improvement or stabilization of keratitis within 48 hours after initiation of treatment.138
For the topical treatment of acute bacterial otitis externa in adults and children 1 year of age and older, the contents of a single-use container of ciprofloxacin 0.2% otic solution (0.25 mL) should be instilled into the canal of the affected ear(s) twice daily (approximately 12 hours apart) for 7 days.133
When the fixed-combination otic suspension containing ciprofloxacin and dexamethasone (ciprofloxacin 0.3% and dexamethasone 0.1%) is used for the topical treatment of acute bacterial otitis externa in adults and children 6 months of age and older, 4 drops of the otic suspension should be instilled into the canal of the affected ear(s) twice daily for 7 days.125
When the fixed-combination otic suspension containing ciprofloxacin and hydrocortisone (ciprofloxacin 0.2% and hydrocortisone 1%) is used for the topical treatment of acute bacterial otitis externa in adults and children 1 year of age and older, 3 drops of the otic suspension should be instilled into the canal of the affected ear(s) twice daily for 7 days.120
The optimal duration of topical therapy for the treatment of acute otitis externa has not been determined, but 7-10 days is usually recommended.139 Some experts state that appropriate treatment of acute otitis externa should result in improvement in symptoms (otalgia, itching, fullness) within 48-72 hours, although resolution of symptoms may take up to 2 weeks.139 The manufacturers state that if there is no improvement in acute otitis externa after 1 week of treatment, cultures should be used to help guide further treatment.120, 125, 133 (See Precautions Related to Otic Administration under Cautions: Precautions and Contraindications.)
When the fixed-combination otic suspension containing ciprofloxacin and dexamethasone (ciprofloxacin 0.3% and dexamethasone 0.1%) is used for the topical treatment of acute otitis media in pediatric patients 6 months of age or older with tympanostomy tubes, 4 drops of the otic suspension should be instilled through the tympanostomy tube in the affected ear(s) twice daily for 7 days.125
When the fixed-combination otic solution containing ciprofloxacin and fluocinolone acetonide (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%) is used for the topical treatment of acute otitis media in pediatric patients 6 months of age or older with tympanostomy tubes, the contents of a single-dose vial (0.25 mL) of the otic solution should be instilled into the canal of the affected ear(s) twice daily (approximately every 12 hours) for 7 days.126
For the treatment of bilateral otitis media with effusion in pediatric patients 6 months of age or older undergoing tympanostomy tube placement, a single dose of 0.1 mL (6 mg) of ciprofloxacin 6% otic suspension should be administered intratympanically into each affected ear.127
Ciprofloxacin ophthalmic and otic preparations generally are well tolerated following topical application.1, 3, 25, 119, 120, 125, 133 In most cases, adverse effects reported with topical ciprofloxacin therapy have been mild and have resolved without specific treatment.25, 115, 116
Overall, the most frequent adverse effects following topical application of ciprofloxacin ophthalmic solution or ointment are transient ocular discomfort (e.g., burning, stinging).1, 3, 25, 119, 134 Such effects have been reported in approximately 10% of patients in clinical studies receiving ciprofloxacin ophthalmic solution for various ophthalmic conditions.25, 115 Ocular discomfort occurred in 2% of patients receiving ciprofloxacin ophthalmic ointment.119
In patients with bacterial keratitis (corneal ulcers), the principal reported ocular effect has been the development of a white granular or crystalline precipitate in the superficial portion of the corneal defect,1, 3, 25, 134 being observed in approximately 17% of patients with keratitis treated with ciprofloxacin ophthalmic solution in clinical studies.1, 3, 25, 134 This corneal precipitate, identified as ciprofloxacin, generally appears during the early intensive phase of therapy for keratitis (e.g., within 1-7 days of initiating therapy) when the solution is administered repeatedly at relatively short intervals1, 3, 134 and usually resolves during the later phase of continued therapy when dosage (e.g., frequency of administration) of the drug is reduced.1, 3, 25, 134 Presence of this precipitate does not appear to preclude continued therapy with ciprofloxacin nor to affect visual outcome or the clinical course of the corneal ulcer,1, 3, 25, 115, 116, 117, 134 and adjunctive therapy for its management is not necessary.25 In one study in patients with bacterial keratitis, the precipitate was observed more frequently in geriatric patients (older than 60 years of age) than in younger patients, but the risk of development appeared to be unrelated to gender, stromal depth of the ulcer or infiltrate, organism cultured, or time to resolution of infection.25 Factors contributing to ocular precipitation of ciprofloxacin, other than dosage (e.g., frequency of administration), remain to be elucidated.25
Other adverse ocular effects have been reported in less than 10% of patients receiving topical ciprofloxacin ophthalmic solution in clinical studies and include lid margin crusting,1, 3, 134 crystals/scales on eyelashes,1, 3, 25, 134 foreign body sensation,1, 3, 25, 134 itching,1, 3, 25, 134 and conjunctival hyperemia.1, 3, 25, 134 Corneal staining,1, 25, 134 keratopathy/keratitis,1, 25, 134 allergic reactions,1, 134 lid edema,1, 25, 134 tearing,1, 25, 134 photophobia,1, 25, 134 decrease in vision,1, 134 and corneal infiltrates1, 25, 134 have been reported in less than 1% of patients.1, 3, 25, 134
Keratopathy has been reported in 2% of patients receiving topical ciprofloxacin ophthalmic ointment.119 Allergic reactions,119 blurred vision,119 corneal staining,119 decreased visual acuity,119 dry eye,119 edema,119 epitheliopathy,119 ocular pain,119 foreign body sensation,119 hyperemia,119 irritation,119 keratoconjunctivitis,119 lid erythema,119 lid margin hyperemia,119 photophobia,119 pruritus,119 or tearing119 was reported in less than 1% of patients receiving topical ciprofloxacin ophthalmic ointment.119
Since systemic absorption may occur following topical application of ciprofloxacin to the eye,1, 3 the possibility of adverse systemic effects exists.1, 115
Taste abnormality (e.g., bad taste in the mouth) has been reported1, 25, 134 in 5% of patients in clinical studies receiving topical application of ciprofloxacin ophthalmic solution to the eye for various ophthalmic conditions.25 Taste abnormality119 or dermatitis119 has occurred in less than 1% of patients receiving ciprofloxacin ophthalmic ointment.119 Nausea has been reported in less than 1% of patients receiving the ophthalmic solution or ointment.1, 119
Following topical administration of ciprofloxacin 0.2% otic solution in patients with acute otitis externa, application site pain, ear pruritus, and fungal ear superinfection were reported in 2-3% of patients.133
Otic discomfort, pain, or pruritus has been reported in 1.5-4% of patients receiving the fixed-combination otic suspension containing ciprofloxacin and dexamethasone (ciprofloxacin 0.3% and dexamethasone 0.1%).125
Otorrhea was reported in 5% and ear infection, ear pruritus, and tympanic membrane disorder were each reported in 1% of patients receiving the fixed-combination otic solution containing ciprofloxacin and fluocinolone acetonide (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%).126
Ear canal erythema, ear congestion, hypoacusis, and medication residue have been reported rarely in patients receiving the fixed-combination otic suspension containing ciprofloxacin and hydrocortisone (ciprofloxacin 0.2% and hydrocortisone 1%).120
Headache was reported in 2-3% of patients receiving ciprofloxacin 0.2% otic solution.133
Taste perversion and irritability were reported rarely in patients receiving the fixed-combination otic suspension containing ciprofloxacin and hydrocortisone.125
Headache120 or pruritus120 occurred in 1.2 or 0.4% of patients, respectively, receiving the fixed-combination otic suspension of ciprofloxacin and hydrocortisone;120 dizziness,120 migraine headache,120 hypoesthesia,120 paresthesia,120 fungal dermatitis,120 cough,120 rash,120 urticaria,120 and alopecia120 also have been reported.
There was no evidence of cochlear toxicity when the fixed-combination otic suspension of ciprofloxacin and hydrocortisone was administered intratympanically twice daily for 30 days in guinea pigs.120
Otic Administration (Intratympanic)
Nasopharyngitis, irritability, and rhinorrhea have been reported in 3-5% of patients following intratympanic administration of ciprofloxacin 6% otic suspension.127
There was no evidence of drug-related structural or functional changes of the cochlear hair cells when the ciprofloxacin 6% otic suspension was administered into the middle ear in guinea pigs.127
Precautions and Contraindications
Ciprofloxacin 0.3% ophthalmic solution and 0.3% ophthalmic ointment are contraindicated in patients hypersensitive to ciprofloxacin or any ingredient in the formulation.1, 119, 134 These preparations also may be contraindicated in patients hypersensitive to other quinolones.1, 119, 134
Ciprofloxacin 0.2% otic solution for topical use is contraindicated in patients hypersensitive to ciprofloxacin.133
Ciprofloxacin 6% otic suspension for intratympanic use is contraindicated in patients hypersensitive to ciprofloxacin, other quinolones, or any ingredient in the formulation.127
The fixed-combination ciprofloxacin and dexamethasone otic suspension (ciprofloxacin 0.3% and dexamethasone 0.1%) is contraindicated in patients hypersensitive to ciprofloxacin, other quinolones, or any ingredient in the formulation.125 In addition, the fixed combination is contraindicated in patients with viral infections of the external ear canal, including herpes simplex infections, or fungal otic infections.125
The fixed-combination ciprofloxacin and fluocinolone acetonide otic solution (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%) is contraindicated in patients hypersensitive to ciprofloxacin or other quinolones, fluocinolone acetonide or other corticosteroids, or any ingredient in the formulation.126 In addition, the fixed combination is contraindicated in patients with viral infections of the external ear canal, including varicella and herpes simplex infections, or fungal otic infections.126
The fixed-combination ciprofloxacin and hydrocortisone otic suspension (ciprofloxacin 0.2% and hydrocortisone 1%) is contraindicated in patients hypersensitive to hydrocortisone, ciprofloxacin, or other quinolones.120 In addition, the fixed combination is contraindicated in patients with viral infections of the external ear canal, including varicella and herpes simplex infections.120 Unlike other otic preparations containing ciprofloxacin,133, 125, 126 the otic suspension containing ciprofloxacin and hydrocortisone is nonsterile and should not be used if the tympanic membrane is known or suspected to be perforated.120
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving systemic quinolones, including systemic ciprofloxacin, and these reactions have been reported following the initial systemic dose.1, 37, 119, 120, 125, 126, 133, 134 (See Cautions: Dermatologic and Sensitivity Reactions, in Ciprofloxacin 8:12.18.) Patients receiving ciprofloxacin ophthalmic or otic preparations should be advised of this possibility and instructed to discontinue the drug and contact a clinician at the first sign of rash or any other sign of hypersensitivity.1, 116, 119, 120, 125, 126, 133, 134 Serious acute hypersensitivity (anaphylactic) reactions require immediate emergency treatment;1, 119, 120, 126, 134 appropriate therapy (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, maintenance of blood pressure) should be initiated as clinically indicated.1, 119, 134
As with other anti-infectives, prolonged use of ciprofloxacin or fixed-combination preparations containing ciprofloxacin may result in overgrowth of nonsusceptible organisms, including fungi.1, 119, 120, 125, 126, 127, 133, 134 If superinfection occurs, the drug should be discontinued and appropriate therapy instituted.1, 119, 125, 126, 127, 133, 134
Precautions Related to Ophthalmic Administration
When ciprofloxacin ophthalmic solution or ointment is used for the topical treatment of bacterial ophthalmic infections, examination with slit lamp microscopy and, when appropriate, fluorescein staining should be performed as clinically indicated.1, 119, 134
The manufacturer cautions that ophthalmic ointments may retard corneal healing and cause visual blurring.119
Contact lenses should not be worn during treatment with ciprofloxacin ophthalmic solution.1, 134
Precautions Related to Otic Administration
When ciprofloxacin otic preparations, including fixed-combination preparations containing ciprofloxacin and a corticosteroid, are used for the topical treatment of bacterial otic infections, cultures should be obtained to guide further treatment if the infection has not improved after 1 week of therapy.120, 125, 126, 133
If otorrhea persists after completion of topical ciprofloxacin therapy or if 2 or more episodes of otorrhea occur within 6 months, further evaluation is indicated to exclude underlying conditions such as cholesteatoma, foreign body, or tumor.125, 126
The fixed-combination otic suspension containing ciprofloxacin and hydrocortisone should not be used if the tympanic membrane is known or suspected to be perforated.120
When ciprofloxacin 6% otic suspension is used intratympanically in patients with otitis media with effusion undergoing tympanostomy tube placement, patients and/or their caregiver should be advised that there may be drainage from the ear during the first few days following ear tube surgery; however, a clinician should be consulted if there is continuous ear discharge or if the ear becomes painful or fever develops.127
Precautions Related to Use of Fixed Combinations Containing Corticosteroids
When otic preparations containing ciprofloxacin in fixed combination with a corticosteroid (i.e., dexamethasone, fluocinolone acetonide, or hydrocortisone) are used, the usual cautions, precautions, and contraindications associated with the corticosteroid also must be considered.120, 125, 126
Ciprofloxacin 0.3% ophthalmic solution: Safety and efficacy in pediatric patients is supported by evidence from adequate and well-controlled studies in adults, children, and neonates.1 One manufacturer states that safety and efficacy of the ophthalmic solution have not been established in pediatric patients younger than 1 year of age.134
Ciprofloxacin 0.3% ophthalmic ointment: Safety and efficacy have not been established in pediatric patients younger than 2 years of age.119
Ciprofloxacin 0.2% otic solution: Safety and efficacy have not been established in pediatric patients younger than 1 year of age.133
Ciprofloxacin 6% otic suspension for intratympanic use: Safety and efficacy have not been established in pediatric patients younger than 6 months of age.127
Fixed-combination ciprofloxacin and dexamethasone otic suspension (ciprofloxacin 0.3% and dexamethasone 0.1%): Safety and efficacy have not been established in pediatric patients younger than 6 months of age.125
Fixed-combination ciprofloxacin and fluocinolone acetonide otic solution (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%): Safety and efficacy have not been established in pediatric patients younger than 6 months of age.126
Fixed-combination ciprofloxacin and hydrocortisone otic suspension (ciprofloxacin 0.2% and hydrocortisone 1%): Safety and efficacy have not been established in pediatric patients younger than 2 years of age.120 However, efficacy for use in those 1 year of age and older has been extrapolated based on studies in adults and older pediatric patients.120
Quinolones, including ciprofloxacin, have caused arthropathy in immature animals of various species following oral administration.1, 5, 36, 55, 100, 119, 134 In young beagles, ciprofloxacin given in a dosage of 100 mg/kg daily for 4 weeks caused degenerative articular changes in the knee joint; in a daily dosage of 30 mg/kg, effects on the joint were minimal, although some damage to weight-bearing joints was observed even at the lower dosage.37, 100 However, topical application of a ciprofloxacin ophthalmic preparation for 1 month to the eye(s) of young beagles did not cause arthropathy or have any effects on weight-bearing joints.1, 119, 134 In addition, there is no evidence that topical application of otic preparations of quinolones has any effect on weight-bearing joints.133
No evidence of cochlear toxicity was observed when the fixed-combination ciprofloxacin and hydrocortisone otic suspension was administered intratympanically twice daily for 30 days in guinea pigs.120
No overall differences in safety and efficacy of ciprofloxacin 0.3% ophthalmic solution, ciprofloxacin 0.3% ophthalmic ointment, or ciprofloxacin 0.2% otic solution have been observed between geriatric and younger adults.1, 119, 133, 134
Clinical studies of the fixed-combination ciprofloxacin and fluocinolone acetonide otic solution (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%) did not include sufficient numbers of patients 65 years of age or older to determine whether they respond differently than younger patients.126 Other reported clinical experience has not identified differences in responses between geriatric and younger patients.126
Mutagenicity and Carcinogenicity
Ciprofloxacin was not mutagenic in vivo in the rat hepatocyte DNA repair assay or dominant lethal or micronucleus tests in mice.1, 3, 115, 119, 120, 125, 126, 127, 133, 134 Ciprofloxacin was positive for mutagenicity in the mouse lymphoma cell forward mutation assay and in vitro in the rat hepatocyte DNA repair assay; however, the drug was not mutagenic in other in vitro studies, including the Ames microbial ( Salmonella ) mutagen test with metabolic activation, Escherichia coli DNA repair assay, Chinese hamster V-79 cell HGPRT test, Syrian hamster embryo cell transformation assay, Saccharomyces cerevisiae point mutation assay, and mitotic crossover and gene conversion assays.1, 3, 115, 119, 120, 125, 126, 127, 133, 134
No evidence of carcinogenic potential was seen in mice and rats receiving oral ciprofloxacin daily for up to 2 years.1, 119, 120, 125, 126, 127, 133, 134
Pregnancy, Fertility, and Lactation
There are no adequate and controlled studies to date using ciprofloxacin ophthalmic solution or ointment in pregnant women, and these preparations should be used during pregnancy only when potential benefits justify possible risks to the fetus.1, 119, 134
There are no adequate and controlled studies using ciprofloxacin otic preparations, including fixed-combination preparations containing ciprofloxacin and a corticosteroid, in pregnant women, and these preparations should be used with caution during pregnancy.120, 125, 133 The manufacturer of the fixed combination of ciprofloxacin and fluocinolone acetonide states that negligible amounts of ciprofloxacin or fluocinolone acetonide are absorbed following topical administration of the otic solution and use of the fixed combination during pregnancy is not expected to result in fetal exposure to either drug.126
Animal reproduction studies have not been performed using ciprofloxacin 6% otic suspension for intratympanic use and there are no adequate and well-controlled studies using the preparation in pregnant women.127 The manufacturer states that negligible systemic exposure is expected following intratympanic administration of the 6% otic suspension and there is minimal risk for maternal and fetal toxicity if the otic suspension is used during pregnancy.127
Reproduction studies in rats and mice receiving oral ciprofloxacin dosages up to 6 times the usual human oral dosage have not revealed evidence of harm to the fetus.1, 119, 120, 134 In rabbits, oral ciprofloxacin dosages of 30 and 100 mg/kg caused adverse GI effects resulting in maternal weight loss and an increased incidence of abortion, but there was no evidence of teratogenicity at either dosage.1, 119, 120, 134 IV ciprofloxacin given to rabbits in dosages up to 20 mg/kg has not resulted in maternal toxicity, embryotoxicity, or teratogenicity.1, 119, 120, 134
Reproduction studies in rats and mice using oral ciprofloxacin dosages up to 6 times the usual human oral dosage have not revealed evidence of impaired fertility.1, 119, 120, 134
It is not known whether ciprofloxacin is distributed into milk following topical application to the eye or ear; however, ciprofloxacin is distributed into milk following oral administration.1, 119, 120, 127, 133, 134
Ciprofloxacin ophthalmic preparations should be used with caution in nursing women.1, 119, 134
Because of the potential for serious adverse reactions to the drug in nursing infants, a decision should be made whether to discontinue nursing or otic preparations containing ciprofloxacin, including fixed-combinations preparations containing ciprofloxacin and a corticosteroid, taking into account the importance of the drug to the woman.120, 125, 133 The manufacturer of the fixed combination of ciprofloxacin and fluocinolone acetonide states that negligible amounts of ciprofloxacin and fluocinolone acetonide are absorbed following topical administration of the otic solution and use of the fixed-combination otic solution in the woman is not expected to result in exposure to either drug in her breast-feeding infant.126
The manufacturer of ciprofloxacin 6% otic suspension for intratympanic use states that breast-feeding infants of women treated with the otic preparation should not be affected since negligible systemic exposure is expected in the woman.127
Specific drug interaction studies have not been performed using ciprofloxacin ophthalmic preparations.1, 119, 134 However, since systemic absorption may occur following topical application of ciprofloxacin to the eye, the manufacturers state that the possibility of drug interactions such as those reported with some systemic quinolones (e.g., interactions with theophylline, caffeine, oral anticoagulants, cyclosporine) should be considered.1, 119, 134 (See Drug Interactions in Ciprofloxacin 8:12.18.)
Information is not available regarding overdosage of topical ciprofloxacin in humans;1 one manufacturer states that overdosage following oral ingestion of the commercially available ophthalmic solution is unlikely given the limited amount of ciprofloxacin present in the solution.115 In case of topical overdosage of ciprofloxacin ophthalmic solution, the eye(s) may be flushed with warm tap water.1, 134
Some manufacturers state that toxic effects are not expected following overdosage of otic preparations containing ciprofloxacin.125, 126
Results of in vitro studies using rabbit corneal epithelial cell cultures indicate that a 0.3% solution of ciprofloxacin does not damage epithelial cells.107 Ocular toxicity studies in rabbits suggest that intravitreal injection of ciprofloxacin 100 mcg does not result in permanent retinal dama 12, 105 however, retinal toxicity has occurred following intravitreal injection of higher dosages.105 In addition, corneal toxicity has been documented in rabbits following injection of at least 25 mcg of ciprofloxacin into the anterior chamber of the eye or intravitreal injection of 100 mcg of the drug.105
Ciprofloxacin usually is bactericidal in action.1, 3, 37, 40, 41, 42, 43, 44, 45, 47, 55 Like other fluoroquinolone anti-infectives, ciprofloxacin inhibits DNA synthesis in susceptible organisms via inhibition of type II DNA topoisomerases (DNA gyrase, topoisomerase IV).1, 3, 7, 31, 36, 37, 43, 44, 50, 51, 52, 53
Ciprofloxacin is active in vitro against most gram-negative aerobic bacteria and many gram-positive aerobic bacteria,1, 3, 5, 8, 30, 31, 32, 40, 42, 46, 54 including penicillinase-producing, nonpenicillinase-producing, and methicillin-resistant staphylococci (also known as oxacillin-resistant staphylococci);1, 3, 5, 8, 30, 31, 40, 42, 46, 59, 60 the drug generally is less active against gram-positive than gram-negative bacteria30, 31, 42, 46, 67, 68, 69 and is less active in vitro on a weight basis against streptococci than against staphylococci.3, 5, 8, 40, 42, 55, 64, 65, 66, 67, 68 Most strains of Pseudomonas cepacia , some strains of Ps. maltophilia , and most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile , are resistant to the drug.1, 3 Ciprofloxacin is inactive against fungi and viruses.1, 3, 5, 8, 55
In vitro, ciprofloxacin concentrations of 1 mcg/mL or less inhibit most strains of the following ocular pathogens: Acinetobacter calcoaceticus ,3, 5, 8, 64, 65, 66, 67, 69 Chlamydia trachomatis ,3, 5, 8, 55, 73, 74, 75 Citrobacter spp.,3, 5, 8, 55, 64, 65, 66, 69 Enterobacter spp.,3, 5, 8, 42, 55, 63, 64, 65, 66, 67, 69 Escherichia coli ,3, 5, 8, 42, 55, 64, 65, 67, 69 Haemophilus influenzae ,3, 5, 8, 32, 55, 63, 64, 65, 68, 69 Klebsiella pneumoniae ,3, 5, 8, 55, 64, 65, 66, 67, 69 Mycobacterium tuberculosis ,3, 5, 8, 32, 70, 71, 72 Neisseria spp.,3, 5, 8, 32, 55, 61, 64, 65, 67, 69 Proteus spp.,3, 5, 8, 32, 42, 55, 63, 64, 65, 66, 67, 69 Pseudomonas aeruginosa ,3, 5, 8, 32, 42, 55, 61, 63, 64, 65, 66, 67, 68, 69 Staphylococcus aureus ,3, 5, 8, 32, 42, 55, 61, 62, 63, 64, 65, 66, 67 S. epidermidis ,3, 5, 8, 42, 55, 63, 64, 65, 66, 67 and Serratia marcescens .3, 5, 63, 64, 65, 66, 67, 69 Susceptible strains of Streptococcus pneumoniae 3, 5, 8, 40, 42, 55, 64, 65, 66, 67, 68 and viridans streptococci3, 5, 8, 40, 42, 55, 64, 66 are inhibited by ciprofloxacin concentrations of 4 mcg/mL or less.
In vitro, ciprofloxacin usually is more active than tobramycin against Ps. aeruginosa , Staphylococcus , and Streptococcus and at least as active as tobramycin against Serratia .3 Ciprofloxacin also is more active than norfloxacin against susceptible bacteria in vitro,5, 55, 107 and the drug has shown greater activity than norfloxacin in some in vivo models of bacterial keratitis caused by Ps. aeruginosa .9, 110 Ciprofloxacin has demonstrated in vivo activity against most strains of Staphylococcus aureus (including oxacillin-resistant strains), S. epidermidis , Streptococcus pneumoniae , viridans streptococci, Ps. aeruginosa , and Serratia marcescens in a limited number of clinical studies in patients with ocular infections.1, 3, 25, 27
Resistance to ciprofloxacin can be produced in vitro in some strains of Enterobacteriaceae, Pseudomonas aeruginosa , Staphylococcus aureus , and Enterococcus faecalis (formerly Streptococcus faecalis ), by serial passage in the presence of increasing concentrations of the drug.5, 8, 31, 32, 40, 42, 44, 55, 61, 67, 76, 77, 78 Ciprofloxacin resistance resulting from spontaneous mutation occurs rarely in vitro (i.e., with a frequency of 109 to 107).3, 5, 8, 31, 32, 44, 55, 67, 76 However, resistant strains of Ps. aeruginosa 5, 8, 30, 32, 55, 79, 80 and staphylococci5, 8, 55, 81, 82, 83 have emerged during systemic therapy with the drug. Spontaneous resistance to ciprofloxacin is concentration dependent, generally occurring only when the MIC for the organism exceeds the concentration of the drug at the infection site by several (e.g., 4-8)-fold.55, 116 Therefore, the potential for development of resistance to ciprofloxacin during ophthalmic administration is likely to be less than that associated with systemic drug administration because of the relatively high drug concentrations achieved in ocular tissue with administration of commercially available ciprofloxacin ophthalmic solution.55
Cross-resistance can occur between ciprofloxacin and other fluoroquinolones.126
In all studies described in the Pharmacokinetics section, ciprofloxacin was administered as the hydrochloride salt; dosages and concentrations of the drug are expressed in terms of ciprofloxacin.1, 8, 9, 11, 55
The extent of ocular and systemic absorption of ciprofloxacin following topical application to the eye has not been fully elucidated; however, serum concentrations achieved following such application to uninflamed eyes are minimal relative to those produced by usual oral or parenteral doses of the drug.1, 3, 115, 116 Following topical application to the eye, ciprofloxacin is absorbed through the cornea into aqueous humor;8, 9, 11, 55 absorption is enhanced in the presence of ocular inflammation and/or epithelial defects.10, 11, 114
Following topical application to the eye of 1 drop of a 0.3% solution of ciprofloxacin (150 mcg) every 15 minutes for 1 hour and then every hour for 10 hours in patients undergoing keratoplasty, concentrations of the drug in corneal stromal tissue harvested within 1 hour after the last dose of ciprofloxacin averaged 5.28 mcg/g (range: 1.4-10.6 mcg/g).10 In anesthetized rabbits with intact ocular epithelium, topical application to the eye of 1 drop of a 0.3% solution of ciprofloxacin every 30 minutes for 6 doses produced aqueous humor concentrations averaging approximately 4.8 and 3.1 mcg/mL 30 and 90 minutes, respectively, after the last dose; in rabbits with ocular epithelial defects, aqueous humor concentrations averaged 12.9 and 7 mcg/mL 30 and 90 minutes, respectively, after application of the last dose.11 Following topical application to the eye of 1 drop of ciprofloxacin 0.75% every 15 minutes for 4 doses and then every 30 minutes for 3 hours in anesthetized rabbits, drug concentrations in aqueous humor 1 hour after the last dose averaged 30.5 mcg/mL.9 Following intravitreal injection of 100 mcg of ciprofloxacin in rabbits, peak drug concentrations in aqueous and vitreous humor at 1 hour were approximately 0.6 and 27.3 mcg/mL, respectively.12
Some systemic absorption of ciprofloxacin occurs following topical application of the drug to the eyes.1, 3 Following topical application to the eyes in healthy adults of 1 drop of a 0.3% solution of ciprofloxacin every 2 hours while awake for 2 days, then every 4 hours while awake for 5 days, serum ciprofloxacin concentrations reportedly ranged from undetectable to 4.7 ng/mL25 but generally averaged less than 2.5 ng/mL.1, 3, 115 In contrast, peak serum concentrations generally average 0.8-1.5 mcg/mL (800-1500 ng/mL) following administration of a single 250-mg oral dose of ciprofloxacin in healthy, fasting adults.8, 87, 88, 89, 90, 91
The extent of systemic absorption of ciprofloxacin following topical administration of ciprofloxacin ophthalmic ointment has not been fully evaluated.119 Based on studies using ciprofloxacin 0.3% ophthalmic solution, the maximum plasma ciprofloxacin concentration following application of the ophthalmic ointment is expected to average less than 2.5 ng/mL.119
The manufacturer of ciprofloxacin 0.2% otic solution states that plasma concentrations of the drug have not been measured following topical otic application of the solution; however, peak plasma concentrations following topical otic application are expected to be less than 5 ng/mL.133
Following topical application of 4 drops of the fixed-combination otic suspension containing ciprofloxacin and dexamethasone (ciprofloxacin 0.3% and dexamethasone 0.1%) into each ear canal in pediatric patients with tympanostomy tubes, peak plasma concentrations of ciprofloxacin ranged from 0.54-3.45 ng/mL (mean: 1.39 ng/mL).125 These peak plasma concentrations were on average approximately 0.1% of peak plasma concentrations of ciprofloxacin attained following a 250-mg oral dose of the drug.125
Following topical application of the fixed-combination otic solution containing ciprofloxacin and fluocinolone acetonide (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%) into the ears of pediatric patients 6 months to 12 years of age with acute otitis media with tympanostomy tubes (0.75 mg of ciprofloxacin and 0.0625 mg of fluocinolone acetonide twice daily), ciprofloxacin and fluocinolone acetonide were undetectable in the plasma of almost all patients.126 In one patient with bilateral acute otitis media, plasma concentrations of ciprofloxacin were 3 mcg/mL after 7 days of treatment, but the corticosteroid was undetectable.126
The manufacturer of the fixed-combination otic suspension containing ciprofloxacin and hydrocortisone (ciprofloxacin 0.2% and hydrocortisone 1%) states that plasma concentrations of ciprofloxacin following topical otic application of 3 drops of the fixed combination are expected to be lower than the limit of detection of the assay (50 ng/mL) and peak plasma concentrations of hydrocortisone are predicted to be within the range of endogenous hydrocortisone.120
Otic Administration (Intratympanic)
The manufacturer of ciprofloxacin 6% otic suspension for intratympanic use states that plasma concentrations of ciprofloxacin have not been measured following bilateral intratympanic administration of 0.1-mL doses of the suspension.127 Because the commercially available ciprofloxacin 6% otic suspension contains poloxamer 407, a thermosensitive polymer, the suspension exists as a liquid at room temperature and transitions to a gel when exposed to body temperature in the middle ear.142, 144 This allows ciprofloxacin to be solubilized over time and results in sustained exposure to the drug in the middle ear.127, 142, 144
Distribution of ciprofloxacin into human ocular tissues and fluids following topical ophthalmic administration has not been fully characterized to date.8, 17 Limited data in animals with experimentally induced ocular infection and in patients with intact corneal epithelium suggest that the drug penetrates into the cornea and other ocular tissues (e.g., aqueous humor) following topical application of a 0.3% solution of ciprofloxacin and is present in these tissues at concentrations exceeding the MIC of most corneal and conjunctival pathogens; the presence of ocular epithelial defects would likely result in enhanced penetration of the drug into ocular tissues.9, 10, 11, 55, 114
Ciprofloxacin is widely distributed into body tissues and fluids following oral or IV administration.5, 30, 32, 34, 37, 55 (See Pharmacokinetics: Distribution, in Ciprofloxacin 8:12.18.) Information on the distribution of ciprofloxacin into ocular tissues and fluids following systemic administration of the drug is based principally on studies in patients with uninflamed and/or uninfected eyes; distribution is likely to be greater in the presence of inflammation or infection because of disruption of the blood/ocular barrier.17, 114, 115, 116 Following oral or IV administration of ciprofloxacin in patients undergoing cataract extraction, peak drug concentrations in aqueous humor generally have averaged 3-33% of concurrent serum concentrations.8, 14, 15, 16, 17, 21 Following single-dose oral or IV administration of ciprofloxacin in patients undergoing ocular surgery, concentrations in vitreous humor averaged about 20% of concurrent serum concentrations.17, 18 Following IV administration of a single 12-mg dose of the drug in rabbits, ciprofloxacin concentrations in aqueous or vitreous humor averaged approximately 10 or approximately 1-5%, respectively, of concurrent serum concentrations.13
Ciprofloxacin is 16-43% bound to serum proteins in vitro.5, 30, 32, 34, 37, 45, 92, 93
Ciprofloxacin crosses the placenta and is distributed into amniotic fluid in humans;94 the drug also is distributed into milk.19, 20, 94 (See Pharmacokinetics: Distribution, in Ciprofloxacin 8:12.18.)
The metabolic fate and elimination characteristics of ciprofloxacin following topical application to the eye have not been elucidated.115 In a study in rabbits, the half-life of ciprofloxacin in aqueous humor was 1-2 hours.11 The serum elimination half-life of ciprofloxacin in adults with normal renal function is 3-5 hours.5, 34, 37, 46, 90
Systemically absorbed ciprofloxacin is eliminated by renal and nonrenal mechanisms.5, 30, 34, 37 The drug is partially metabolized in the liver to at least 4 metabolites;5, 30, 34, 37 these metabolites have microbiologic activity that is less than that of ciprofloxacin32, 34, 37, 96 but may be similar to or greater than that of other quinolones.95, 96 Ciprofloxacin and its metabolites are excreted in urine5, 30, 32, 34, 35, 46 and feces.5, 34, 37 Unchanged ciprofloxacin is excreted in urine by both glomerular filtration and tubular secretion.5, 30, 32, 34, 35, 46 Most, but not all, unchanged ciprofloxacin in feces appears to result from biliary excretion.97, 98
Ciprofloxacin is a fluoroquinolone anti-infective agent.1, 3, 5, 8, 55, 119, 125, 126, 127, 133, 134 Like other commercially available fluoroquinolones, ciprofloxacin contains a fluorine at position 6 of the quinolone nucleus.1, 5, 30, 31, 32, 33, 34, 35, 36, 37, 38 Like some other fluoroquinolones (gatifloxacin, levofloxacin, norfloxacin, ofloxacin), ciprofloxacin contains a piperazinyl group at position 7 of the quinolone nucleus. 3, 5, 8, 32, 33, 37, 38 The piperazinyl group in ciprofloxacin results in antipseudomonal activity.3, 5, 8, 32, 33, 37, 38 The drug also contains a cyclopropyl group at position 1, which enhances antimicrobial activity.1, 3, 5, 8, 37
Ciprofloxacin is commercially available for topical ophthalmic and topical otic administration as ciprofloxacin hydrochloride, which is the monohydrochloride monohydrate of the drug.1, 119, 120, 125, 126, 133, 134 Potency is expressed in terms of ciprofloxacin rather than in terms of the salt.1, 108, 119, 120, 125, 126, 133, 134 Each 3.5 mg of ciprofloxacin hydrochloride monohydrate1, 134 or 3.33 mg of ciprofloxacin hydrochloride (calculated on the anhydrous basis)119, 122 provides 3 mg of ciprofloxacin.1, 119
Ciprofloxacin hydrochloride occurs as a faintly yellowish to light yellow crystalline powder1, 2, 37 and has solubilities of approximately 36 mg/mL in water at 25°C2, 30 and 0.16 mg/mL in alcohol.2 The pKas of the drug in water are 6 and 8.8.8, 39
For topical ophthalmic use, ciprofloxacin is commercially available as a 0.3% ophthalmic solution1, 134 and a 0.3% ophthalmic ointment.119 For otic use, ciprofloxacin is commercially available as a 0.2% otic solution for topical administration134 and a 6% otic suspension for intratympanic administration.127 Ciprofloxacin also is commercially available for topical otic use in fixed combination with a corticosteroid (i.e., dexamethasone, fluocinolone acetonide, or hydrocortisone).120, 125, 126
Ciprofloxacin 0.3% ophthalmic solution is a sterile, isotonic solution of ciprofloxacin hydrochloride in purified water; hydrochloric acid and/or sodium hydroxide may be added to adjust pH to approximately 4.5.1, 134 The commercially available ophthalmic solution also contains benzalkonium chloride as a preservative, acetic acid, sodium acetate, mannitol, and edetate disodium and has an osmolality of approximately 300 mOsm/kg.1, 134
Ciprofloxacin 0.3% ophthalmic ointment is a sterile ointment containing ciprofloxacin hydrochloride in white petrolatum; the commercially available preparation also contains mineral oil.119
Ciprofloxacin 0.2% otic solution is a sterile, preservative-free solution of ciprofloxacin hydrochloride for topical otic use.133 The otic solution contains povidone and glycerin and may contain sodium hydroxide and/or lactic acid to adjust pH.133
Ciprofloxacin 6% otic suspension is a sterile, isotonic, buffered, preservative-free suspension of ciprofloxacin for intratympanic use.127 The otic suspension contains poloxamer 407, sodium chloride, tromethamine, and hydrochloric acid.127 Because poloxamer 407 is a thermosensitive polymer, the otic suspension exists as a liquid at room temperature and transitions to a gel when exposed to body temperature in the middle ear.142, 144
The fixed combination of ciprofloxacin hydrochloride and dexamethasone (ciprofloxacin 0.3% and dexamethasone 0.1%) is commercially available as a preserved sterile suspension for topical otic use.125 Ciprofloxacin and dexamethasone otic suspension contains benzalkonium chloride as a preservative, boric acid, sodium chloride, hydroxyethyl cellulose, tyloxapol, acetic acid, sodium acetate, edetate disodium, and purified water; sodium hydroxide or hydrochloride acid may be added to adjust pH.125
The fixed combination of ciprofloxacin hydrochloride and fluocinolone acetonide (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%) is commercially available as a sterile, preservative-free solution for topical otic use.126 Ciprofloxacin and fluocinolone acetonide otic solution contains polysorbate 80, glycerin, and povidone K90F and has a pH of 3.5-5.120
The fixed combination of ciprofloxacin hydrochloride and hydrocortisone (ciprofloxacin 0.2% and hydrocortisone 1%) is commercially available as a preserved nonsterile suspension for topical otic use.120 Ciprofloxacin and hydrocortisone otic suspension contains benzyl alcohol as a preservative, polyvinyl alcohol, sodium chloride, sodium acetate, glacial acetic acid, phospholipon 90HB (modified lecithin), polysorbate, and purified water; sodium hydroxide or hydrochloric acid may be added to adjust pH.120
Ciprofloxacin 0.3% ophthalmic solution should be stored at 2-25°C and protected from light.1, 134
Ciprofloxacin 0.3% ophthalmic ointment should be stored at 2-25°C.119
Ciprofloxacin 0.2% otic solution for topical use should be stored at 15-25°C.133 The single-use containers of the otic solution should be protected from light;133 unused containers should be stored in the protective foil pouch.133
Ciprofloxacin 6% otic suspension for intratympanic use should be stored at 2-8°C in the original container and protected from light.127 The otic suspension is thermosensitive and exists as a liquid at room temperature or lower, but thickens (gels) when warmed.127 To prevent thickening, the suspension must be kept cold while doses are prepared and should be placed back in a refrigerator if thickening occurs.127
The fixed-combination otic suspension of ciprofloxacin and dexamethasone (ciprofloxacin 0.3% and dexamethasone 0.1%) should be stored at 20-25°C, but may be exposed to 15-30°C;125 freezing should be avoided.125 The otic suspension should be protected from light.125
The fixed-combination otic solution of ciprofloxacin and fluocinolone acetonide (ciprofloxacin 0.3% and fluocinolone acetonide 0.025%) should be stored at 20-25°C, but may be exposed to 15-30°C.126 The single-dose vials of otic solution should be protected from light;126 vials should be stored in the protective foil pouch and unused vials discarded 7 days after opening the pouch.126
The fixed-combination otic suspension of ciprofloxacin and hydrocortisone (ciprofloxacin 0.2% and hydrocortisone 1%) should be stored at less than 25°C;120 freezing should be avoided.120 The otic suspension should be protected from light.120
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Otic | Suspension, for intratympanic use | 6% | Otiprio® | Otonomy |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Ophthalmic | Ointment | 0.3% (of ciprofloxacin) | Ciloxan® | Alcon |
Solution | 0.3% (of ciprofloxacin)* | Ciloxan® | Alcon | |
Ciprofloxacin Hydrochloride Ophthalmic Solution | ||||
Otic | Solution | 0.3% (of ciprofloxacin) | Cetraxal® | Wraser |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Otic | Solution | 0.3% (of ciprofloxacin) with Fluocinolone Acetonide 0.025% | Otovel® | Arbor |
Suspension | 0.2% (of ciprofloxacin) with Hydrocortisone 1% | Cipro® HC Otic | Alcon | |
0.3% (of ciprofloxacin) with Dexamethasone 0.1% | Ciprodex® | Alcon |
1. Alcon Laboratories. Ciloxan® (ciprofloxacin) 0.3% ophthalmic solution prescribing information. Fort Worth, TX; 2017 Mar.
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3. Alcon Laboratories. Ciloxan® product monograph. Ciloxan® (ciprofloxacin HCl) 0.3% as base sterile ophthalmic solution. Fort Worth, TX: 1991 Apr.
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