OFLOXACIN

Main information

  • Trade name:
  • OFLOXACIN- ofloxacin solution/ drops
  • Composition:
  • OFLOXACIN 3 mg in 1 mL
  • Administration route:
  • OPHTHALMIC
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • OFLOXACIN- ofloxacin solution/ drops
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • Ofloxacin ophthalmic solution is indicated for the treatment of infections caused by susceptible strains of the following bacteria in the conditions listed below: 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 ).
  • Product summary:
  • Product: 50090-0891 NDC: 50090-0891-0 5 mL in a BOTTLE, DROPPER / 1 in a CARTON

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 50090-0891-0
  • Last update:
  • 17-06-2019

Summary of Product characteristics: dosage, interactions, side effects

OFLOXACIN- ofloxacin solution/ drops

A-S Medication Solutions

----------

PRESCRIBING INFORMATION

OFLOXACIN OPHTHALMIC SOLUTION USP, 0.3%

Rx only

DESCRIPTION

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

[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid.

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.

CLINICAL PHARMACOLOGY

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

9.2 mcg/g.

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

aminoglycosides.

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

AEROBES, GRAM-

POSITIVE:

AEROBES, GRAM-NEGATIVE:

ANAEROBIC

SPECIES:

Staphylococcus aureus

Enterobacter cloacae

Propionibacterium acnes

Staphylococcus epidermidis

Haemophilus influenzae

Streptococcus pneumoniae

Proteus mirabilis Pseudomonas aeruginosa

Serratia marcescens*

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.

AEROBES, GRAM-

POSITIVE:

AEROBES, GRAM-NEGATIVE:

OTHER:

Enterococcus faecalis

Acinetobacter calcoaceticus var. anitratus

Chlamydia trachomatis

Listeria monocytogenes

Acinetobacter calcoaceticus var. Iwoffii

Staphylococcus capitis

Citrobacter diversus

Staphylococcus hominus

Citrobacter freundii

Staphylococcus simulans

Enterobacter aerogenes

Streptococcus pyogenes

Enterobacter agglomerans

Escherichia coli

Haemophilus parainfluenzae

Klebsiella oxytoca

Klebsiella pneumoniae

Moraxella (Branhamella) catarrhalis

Moraxella lacunata

Morganella morganii

Neisseria gonorrhoeae

Pseudomonas acidovorans

Pseudomonas fluorescens

Shigella sonnei

Clinical Studies:

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:

CONJUNCTIVITIS:

Gram-positive bacteria:

Gram-negative bacteria:

Staphylococcus aureus

Enterobacter cloacae

Staphylococcus epidermidis

Haemophilus influenzae

Streptococcus pneumoniae

Proteus mirabilis

Pseudomonas aeruginosa

CORNEAL ULCERS:

*Efficacy for this organism was studied in fewer than 10 infections

Gram-positive bacteria:

Gram-negative bacteria:

Anaerobic species:

Staphylococcus aureus

Pseudomonas aeruginosa

Propionibacterium acnes

Staphylococcus epidermidis

Serratia marcescens*

Streptococcus pneumoniae

CONTRAINDICATIONS

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).

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

clinically indicated.

PRECAUTIONS

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

other source.

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

fetus.

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.

ADVERSE REACTIONS

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

eye(s).

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

awake.

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

completion

Instill one to two drops, four times daily.

HOW SUPPLIED

Product: 50090-0891

NDC: 50090-0891-0 5 mL in a BOTTLE, DROPPER / 1 in a CARTON

Ofloxacin

OFLOXACIN

ofloxacin solution/ drops

Product Information

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

OPHTHALMIC

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O FLO XACIN (UNII: A4P49 JAZ9 H) (OFLOXACIN - UNII:A4P49 JAZ9 H)

OFLOXACIN

3 mg in 1 mL

Inactive Ingredients

Ingredient Name

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)

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End

Date

1

NDC:50 0 9 0 -0 8 9 1-

1 in 1 CARTON

11/28 /20 14

1

5 mL in 1 BOTTLE, DROPPER; Type 0 : No t a Co mbinatio n

Pro duc t

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

A-S Medication Solutions

ANDA

ANDA0 76 40 7

0 7/0 1/20 0 8

Labeler -

A-S Medication Solutions (830016429)

Establishment

Name

Ad d re s s

ID/FEI

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)

Revised: 1/2019