OFLOXACIN- ofloxacin solution/ drops
A-S Medication Solutions
OFLOXACIN OPHTHALMIC SOLUTION USP, 0.3%
Ofloxacin Ophthalmic Solution USP, 0.3% is a sterile ophthalmic solution. It is a fluorinated
carboxyquinolone anti-infective for topical ophthalmic use.
Chemical Name: (±)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido
Contains: Active: ofloxacin 0.3% (3 mg/mL);
Preservative: benzalkonium chloride (0.005%);
Inactives: sodium chloride and water for injection. May also contain hydrochloric acid and/or sodium
hydroxide to adjust pH.
Ofloxacin Ophthalmic Solution USP, 0.3% is unbuffered and formulated with a pH of 6.4 (range - 6.0 to
6.8). It has an osmolality of 300 mOsm/kg. Ofloxacin is a fluorinated 4-quinolone which differs from
other fluorinated 4-quinolones in that there is a six member (pyridobenzoxazine) ring from positions 1
to 8 of the basic ring structure.
Pharmacokinetics: Serum, urine and tear concentrations of ofloxacin were measured in 30 healthy
women at various time points during a ten-day course of treatment with ofloxacin ophthalmic solution.
The mean serum ofloxacin concentration ranged from 0.4 ng/mL to 1.9 ng/mL. Maximum ofloxacin
concentration increased from 1.1 ng/mL on day one to 1.9 ng/mL on day 11 after QID dosing for 10 1/2
days. Maximum serum ofloxacin concentrations after ten days of topical ophthalmic dosing were more
than 1000 times lower than those reported after standard oral doses of ofloxacin.
Tear ofloxacin concentrations ranged from 5.7 to 31 mcg/g during the 40 minute period following the
last dose on day 11. Mean tear concentration measured four hours after topical ophthalmic dosing was
Corneal tissue concentrations of 4.4 mcg/mL were observed four hours after beginning topical ocular
application of two drops of ofloxacin ophthalmic solution every 30 minutes. Ofloxacin was excreted in
the urine primarily unmodified.
Microbiology: Ofloxacin has in vitro activity against a broad range of gram-positive and gram-negative
aerobic and anaerobic bacteria. Ofloxacin is bactericidal at concentrations equal to or slightly greater
than inhibitory concentrations. Ofloxacin is thought to exert a bactericidal effect on susceptible
bacterial cells by inhibiting DNA gyrase, an essential bacterial enzyme which is a critical catalyst in the
duplication, transcription, and repair of bacterial DNA.
Cross-resistance has been observed between ofloxacin and other fluoroquinolones. There is generally
no cross-resistance between ofloxacin and other classes of antibacterial agents such as beta-lactams or
Ofloxacin has been shown to be active against most strains of the following organisms both in vitro and
clinically, in conjunctival and/or corneal ulcer infections (see INDICATIONS AND USAGE).
*Efficacy for this organism was studied in fewer than 10 infections
Proteus mirabilis Pseudomonas aeruginosa
The safety and effectiveness of ofloxacin ophthalmic solution in treating ophthalmologic infections due
to the following organisms have not been established in adequate and well-controlled clinical trials.
Ofloxacin ophthalmic solution has been shown to be active in vitro against most strains of these
organisms but the clinical significance in ophthalmologic infections is unknown.
Acinetobacter calcoaceticus var. anitratus
Acinetobacter calcoaceticus var. Iwoffii
Moraxella (Branhamella) catarrhalis
Conjunctivitis: In a randomized, double-masked, multi-center clinical trial, ofloxacin ophthalmic
solution was superior to its vehicle after 2 days of treatment in patients with conjunctivitis and positive
conjunctival cultures. Clinical outcomes for the trial demonstrated a clinical improvement rate of 86%
(54/63) for the ofloxacin treated group versus 72% (48/67) for the placebo treated group after 2 days
of therapy. Microbiological outcomes for the same clinical trial demonstrated an eradication rate for
causative pathogens of 65% (41/63) for the ofloxacin treated group versus 25% (17/67) for the vehicle
treated group after 2 days of therapy. Please note that microbiologic eradication does not always
correlate with clinical outcome in anti-infective trials.
Corneal ulcers: In a randomized, double-masked, multi-center clinical trial of 140 subjects with
positive cultures, ofloxacin ophthalmic solution treated subjects had an overall clinical success rate
(complete re-epithelialization and no progression of the infiltrate for two consecutive visits) of 82%
(61/74) compared to 80% (53/66) for the fortified antibiotic group, consisting of 1.5% tobramycin and
10% cefazolin solutions. The median time to clinical success was 11 days for the ofloxacin treated
group and 10 days for the fortified treatment group.
INDICATIONS AND USAGE
Ofloxacin ophthalmic solution is indicated for the treatment of infections caused by susceptible strains
of the following bacteria in the conditions listed below:
*Efficacy for this organism was studied in fewer than 10 infections
Ofloxacin ophthalmic solution is contraindicated in patients with a history of hypersensitivity to
ofloxacin, to other quinolones, or to any of the components in this medication (see WARNINGS).
NOT FOR INJECTION.
Ofloxacin ophthalmic solution should not be injected subconjunctivally, nor should it be introduced
directly into the anterior chamber of the eye.
There are rare reports of anaphylactic reaction/shock and fatal hypersensitivity reactions in patients
receiving systemic quinolones, some following the first dose, including ofloxacin. Some reactions
were accompanied by cardiovascular collapse, loss of consciousness, angioedema (including
laryngeal, pharyngeal or facial edema), airway obstruction, dyspnea, urticaria, and itching. A rare
occurrence of Stevens-Johnson syndrome, which progressed to toxic epidermal necrolysis, has been
reported in a patient who was receiving topical ophthalmic ofloxacin. If an allergic reaction to
ofloxacin occurs, discontinue the drug. Serious acute hypersensitivity reactions may require immediate
emergency treatment. Oxygen and airway management, including intubation should be administered as
General: As with other anti-infectives, prolonged use may result in overgrowth of nonsusceptible
organisms, including fungi. If superinfection occurs discontinue use and institute alternative therapy.
Whenever clinical judgment dictates, the patient should be examined with the aid of magnification, such
as slit lamp biomicroscopy and, where appropriate, fluorescein staining. Ofloxacin should be
discontinued at the first appearance of a skin rash or any other sign of hypersensitivity reaction.
The systemic administration of quinolones, including ofloxacin, has led to lesions or erosions of the
cartilage in weight-bearing joints and other signs of arthropathy in immature animals of various species.
Ofloxacin, administered systemically at 10 mg/kg/day in young dogs (equivalent to 110 times the
maximum recommended daily adult ophthalmic dose) has been associated with these types of effects.
Information for Patients: Avoid contaminating the applicator tip with material from the eye, fingers or
Systemic quinolones, including ofloxacin, have been associated with hypersensitivity reactions, even
following a single dose. Discontinue use immediately and contact your physician at the first sign of a
rash or allergic reaction.
Drug Interactions: Specific drug interaction studies have not been conducted with ofloxacin
ophthalmic solution. However, the systemic administration of some quinolones has been shown to
elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, and enhance
the effects of the oral anticoagulant warfarin and its derivatives, and has been associated with transient
elevations in serum creatinine in patients receiving cyclosporine concomitantly.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Long term studies to determine the
carcinogenic potential of ofloxacin have not been conducted. Ofloxacin was not mutagenic in the Ames
test, in vitro and in vivo cytogenic assay, sister chromatid exchange assay (Chinese hamster and human
cell lines), unscheduled DNA synthesis (UDS) assay using human fibroblasts, the dominant lethal assay,
or mouse micronucleus assay. Ofloxacin was positive in the UDS test using rat hepatocyte, and in the
mouse lymphoma assay.
In fertility studies in rats, ofloxacin did not affect male or female fertility or morphological or
reproductive performance at oral dosing up to 360 mg/kg/day (equivalent to 4000 times the maximum
recommended daily ophthalmic dose).
Pregnancy: Teratogenic Effects: Ofloxacin has been shown to have an embryocidal effect in rats and
in rabbits when given in doses of 810 mg/kg/day (equivalent to 9000 times the maximum recommended
daily ophthalmic dose) and 160 mg/kg/day (equivalent to 1800 times the maximum recommended daily
ophthalmic dose). These dosages resulted in decreased fetal body weight and increased fetal mortality
in rats and rabbits, respectively. Minor fetal skeletal variations were reported in rats receiving doses of
810 mg/kg/day. Ofloxacin has not been shown to be teratogenic at doses as high as 810 mg/kg/day and
160 mg/kg/day when administered to pregnant rats and rabbits, respectively.
Nonteratogenic Effects: Additional studies in rats with doses up to 360 mg/kg/day during late gestation
showed no adverse effect on late fetal development, labor, delivery, lactation, neonatal viability, or
growth of the newborn.
There are, however, no adequate and well-controlled studies in pregnant women. Ofloxacin ophthalmic
solution should be used during pregnancy only if the potential benefit justifies the potential risk to the
Nursing Mothers: In nursing women a single 200 mg oral dose resulted in concentrations of ofloxacin
in milk which were similar to those found in plasma. It is not known whether ofloxacin is excreted in
human milk following topical ophthalmic administration. Because of the potential for serious adverse
reactions from ofloxacin in nursing infants, a decision should be made whether to discontinue nursing or
to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric use: Safety and effectiveness in infants below the age of one year have not been established.
Quinolones, including ofloxacin, have been shown to cause arthropathy in immature animals after oral
administration; however, topical ocular administration of ofloxacin to immature animals has not shown
any arthropathy. There is no evidence that the ophthalmic dosage form of ofloxacin has any effect on
weight bearing joints.
Geriatric use: No overall differences in safety or effectiveness have been observed between elderly
and younger patients.
Ophthalmic use: The most frequently reported drug-related adverse reaction was transient ocular
burning or discomfort. Other reported reactions include stinging, redness, itching, chemical
conjunctivitis/keratitis, ocular/periocular/facial edema, foreign body sensation, photophobia, blurred
vision, tearing, dryness, and eye pain. Rare reports of dizziness and nausea have been received.
Refer to WARNINGS for additional adverse reactions.
DOSAGE AND ADMINISTRATION
The recommended dosage regimen for the treatment of bacterial conjunctivitis is:
Days 1 and 2
Instill one to two drops every two to four hours in the affected
Days 3 through 7
Instill one to two drops four times daily.
The recommended dosage regimen for the treatment of bacterial corneal ulcer is:
Days 1 and 2
Instill one to two drops into the affected eye every 30 minutes, while
Awaken at approximately four and six hours after retiring and instill one to two drops.
Days 3 through 7 to 9
Instill one to two drops hourly, while awake.
Days 7 to 9 through treatment
Instill one to two drops, four times daily.
NDC: 50090-0891-0 5 mL in a BOTTLE, DROPPER / 1 in a CARTON
ofloxacin solution/ drops
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:50 0 9 0 -0 8 9 1(NDC:17478 -713)
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
O FLO XACIN (UNII: A4P49 JAZ9 H) (OFLOXACIN - UNII:A4P49 JAZ9 H)
3 mg in 1 mL
Stre ng th
So dium Chlo ride (UNII: 451W47IQ8 X)
Hydro chlo ric Acid (UNII: QTT1758 2CB)
So dium Hydro xide (UNII: 55X0 4QC32I)
Wa ter (UNII: 0 59 QF0 KO0 R)
Benza lko nium Chlo ride (UNII: F5UM2KM3W7)
NDC:50 0 9 0 -0 8 9 1-
1 in 1 CARTON
11/28 /20 14
5 mL in 1 BOTTLE, DROPPER; Type 0 : No t a Co mbinatio n
Pro duc t
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
A-S Medication Solutions
ANDA0 76 40 7
0 7/0 1/20 0 8
A-S Medication Solutions (830016429)
Ad d re s s
Busine ss Ope rations
A-S Medicatio n So lutio ns
8 30 0 16 429
RELABEL(50 0 9 0 -0 8 9 1)