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OFLOXACIN | OFLOXACIN [DIRECT RX] | BioPortfolio

13:32 EST 27th January 2019 | BioPortfolio

Note: While we endeavour to keep our records up-to-date one should not rely on these details being accurate without first consulting a professional. Click here to read our full medical disclaimer.

Ofloxacin Otic Solution, 0.3% is a sterile aqueous anti-infective (anti-bacterial) solution for otic use. Chemically, ofloxacin has three condensed 6-membered rings made up of a fluorinated carboxyquinolone with a benzoxazine ring. The chemical name of ofloxacin is: (±)-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. The empirical formula of ofloxacin is C18H20FN3O4 and its molecular weight is 361.38. The structural formula is:

Each mL of Ofloxacin Otic Solution contains 0.3% (3 mg/mL) ofloxacin with benzalkonium chloride (0.0025%), sodium chloride (0.9%), and water for injection. Hydrochloric acid and sodium hydroxide are added to adjust the pH to 6.5 ± 0.5.

Pharmacokinetics:

Drug concentrations in serum (in subjects with tympanostomy tubes and perforated tympanic membranes), in otorrhea, and in mucosa of the middle ear (in subjects with perforated tympanic membranes) were determined following otic administration of ofloxacin solution. In two single-dose studies, mean ofloxacin serum concentrations were low in adult patients with tympanostomy tubes, with and without otorrhea, after otic administration of a 0.3% solution (4.1 ng/mL (n=3) and 5.4 ng/mL (n=5), respectively).

In adults with perforated tympanic membranes, the maximum serum drug level of ofloxacin detected was 10 ng/mL after administration of a 0.3% solution. Ofloxacin was detectable in the middle ear mucosa of some adult subjects with perforated tympanic membranes (11 of 16 subjects). The variability of ofloxacin concentration in middle ear mucosa was high. The concentrations ranged from 1.2 to 602 μg/g after otic administration of a 0.3% solution. Ofloxacin was present in high concentrations in otorrhea (389 - 2850 μg/g, n=13) 30 minutes after otic administration of a 0.3% solution in subjects with chronic suppurative otitis media and perforated tympanic membranes. However, the measurement of ofloxacin in the otorrhea does not necessarily reflect the exposure of the middle ear to ofloxacin.

Microbiology:

Ofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Ofloxacin exerts its antibacterial activity by inhibiting DNA gyrase, a bacterial topoisomerase. DNA gyrase is an essential enzyme which controls DNA topology and assists in DNA replication, repair, deactivation, and transcription. 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 isolates of the following microorganisms, both in vitro and clinically in otic infections as described in the INDICATIONS AND USAGE section.

Aerobic and facultative gram-positive microorganisms:

Staphylococcus aureus

Streptococcus pneumoniae

Aerobic and facultative gram-negative microorganisms:

Escherichia coli

Haemophilus influenzae

Moraxella catarrhalis

Proteus mirabilis

Pseudomonas aeruginosa

Ofloxacin Otic Solution, 0.3% is indicated for the treatment of infections caused by susceptible isolates of the designated microorganisms in the specific conditions listed below:

Otitis Externa in adults and pediatric patients, 6 months and older, due to Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.

Chronic Suppurative Otitis Media in patients 12 years and older with perforated tympanic membranes due to Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus.

Acute Otitis Media in pediatric patients one year and older with tympanostomy tubes due to Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae.

NOT FOR OPHTHALMIC USE.

NOT FOR INJECTION.

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolones, 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. If an allergic reaction to ofloxacin is suspected, stop the drug. Serious acute hypersensitivity reactions may require immediate emergency treatment. Oxygen and airway management, including intubation, should be administered as clinically indicated.

General:

As with other anti-infective preparations, prolonged use may result in over-growth of nonsusceptible organisms, including fungi. If the infection is not improved after one week, cultures should be obtained to guide further treatment. If otorrhea persists after a full course of therapy, or if two or more episodes of otorrhea occur within six months, further evaluation is recommended to exclude an underlying condition such as cholesteatoma, foreign body, or a tumor.

The systemic administration of quinolones, including ofloxacin at doses much higher than given or absorbed by the otic route, has led to lesions or erosions of the cartilage in weight-bearing joints and other signs of arthropathy in immature animals of various species.

Young growing guinea pigs dosed in the middle ear with 0.3% Ofloxacin Otic Solution showed no systemic effects, lesions or erosions of the cartilage in weight-bearing joints, or other signs of arthropathy. No drug-related structural or functional changes of the cochlea and no lesions in the ossicles were noted in the guinea pig following otic administration of 0.3% ofloxacin for one month.

No signs of local irritation were found when 0.3% ofloxacin was applied topically in the rabbit eye. Ofloxacin was also shown to lack dermal sensitizing potential in the guinea pig maximization study.

Information for Patients:

Avoid contaminating the applicator tip with material from the fingers or other sources. This precaution is necessary if the sterility of the drops is to be preserved. 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

Otitis Externa

Prior to administration of Ofloxacin Otic Solution, the solution should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness which may result from the instillation of a cold solution. The patient should lie with the affected ear upward, and then the drops should be instilled. This position should be maintained for five minutes to facilitate penetration of the drops into the ear canal. Repeat, if necessary, for the opposite ear (see DOSAGE AND ADMINISTRATION).

Acute Otitis Media and Chronic Suppurative Otitis Media

Prior to administration of Ofloxacin Otic Solution, the solution should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness which may result from the instillation of a cold solution. The patient should lie with the affected ear upward, and then the drops should be instilled. The tragus should then be pumped 4 times by pushing inward to facilitate penetration of the drops into the middle ear. This position should be maintained for five minutes. Repeat, if necessary, for the opposite ear (see DOSAGE AND ADMINISTRATION).

Drug Interactions:

Specific drug interaction studies have not been conducted with Ofloxacin Otic Solution.

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, the sister chromatid exchange assay (Chinese hamster and human cell lines), the unscheduled DNA synthesis (UDS) assay using human fibroblasts, the dominant lethal assay, or the mouse micro-nucleus assay. Ofloxacin was positive in the rat hepatocyte UDS assay, and in the mouse lymphoma assay. In rats, ofloxacin did not affect male or female reproductive performance at oral doses up to 360 mg/kg/day. This would be over 1000 times the maximum recommended clinical dose, based upon body surface area, assuming total absorption of ofloxacin from the ear of a patient treated with Ofloxacin Otic Solution twice per day.

Pregnancy

Subjects with Otitis Externa

In the phase III clinical trials performed in support of once-daily dosing, 799 subjects with otitis externa and intact tympanic membranes were treated with Ofloxacin Otic Solution. The studies, which served as the basis for approval, were 020 (pediatric, adolescents and adults), 016 (adolescents and adults) and 017 (pediatric). The following treatment-related adverse events occurred in two or more of the subjects.

Incidence Rate

Adverse Event Studies 002/003+ BID (N=229) Studies 016/017+ QD (N=310) Studies 002+ QD (N=489) Application Site Reaction 3% 16.8% 0.6% Pruritus 4% 1.2% 1.0% Earache 1% 0.6% 0.8% Dizziness 1% 0.0% 0.6% Headache 0% 0.3% 0.2% Vertigo 1% 0.0% 0.0%

+Studies 002/003 (BID) and 016/017 (QD) were active-controlled and comparative. Study 020 (QD) was open and non-comparative.

An unexpected increased incidence of application site reaction was seen in studies 016/017 and was similar for both ofloxacin and the active control drug (neomycin-polymyxin B sulfate-hydrocortisone). This finding is believed to be the result of specific questioning of the subjects regarding the incidence of application site reactions.

In once daily dosing studies, there were also single reports of nausea, seborrhea, transient loss of hearing, tinnitus, otitis externa, otitis media, tremor, hypertension and fungal infection.

In twice daily dosing studies, the following treatment-related adverse events were each reported in a single subject: dermatitis, eczema, erythematous rash, follicular rash, hypoaesthesia, tinnitus, dyspepsia, hot flushes, flushing and otorrhagia.

Subjects with Acute Otitis Media with Tympanostomy Tubes (AOM TT) and Subjects with Chronic Suppurative Otitis Media (CSOM) with Perforated Tympanic Membranes In phase III clinical trials which formed the basis for approval, the following treatment-related adverse events occurred in 1% or more of the 656 subjects with non-intact tympanic membranes in AOM TT or CSOM treated twice-daily with Ofloxacin Otic Solution:

Adverse Event

Incidence (N=656)

Taste Perversion 7% Earache 1% Pruritus 1% Paraesthesia 1% Rash 1% Dizziness 1%

Other treatment-related adverse reactions reported in subjects with non-intact tympanic membranes included: diarrhea (0.6%), nausea (0.3%), vomiting (0.3%), dry mouth (0.5%), headache (0.3%), vertigo (0.5%), otorrhagia (0.6%), tinnitus (0.3%), fever (0.3%). The following treatment-related adverse events were each reported in a single subject: application site reaction, otitis externa, urticaria, abdominal pain, dysaesthesia, hyperkinesia, halitosis, inflammation, pain, insomnia, coughing, pharyngitis, rhinitis, sinusitis, and tachycardia.

Post-marketing Adverse Events

Cases of uncommon transient neuropsychiatric disturbances have been included in spontaneous post-marketing reports. A causal relationship with Ofloxacin Otic Solution, 0.3% is unknown.

Otitis Externa: The recommended dosage regimen for the treatment of otitis externa is:

For pediatric patients (from 6 months to 13 years old): Five drops (0.25 mL, 0.75 mg ofloxacin) instilled into the affected ear once daily for seven days.

For patients 13 years and older: Ten drops (0.5 mL, 1.5 mg ofloxacin) instilled into the affected ear once daily for seven days.

The solution should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness which may result from the instillation of a cold solution. The patient should lie with the affected ear upward, and then the drops should be instilled. This position should be maintained for five minutes to facilitate penetration of the drops into the ear canal. Repeat, if necessary, for the opposite ear.

Acute Otitis Media in pediatric patients with tympanostomy tubes: The recommended dosage regimen for the treatment of acute otitis media in pediatric patients (from 1 to 12 years old) with tympanostomy tubes is:

Five drops (0.25 mL, 0.75 mg ofloxacin) instilled into the affected ear twice daily for ten days. The solution should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness which may result from the instillation of a cold solution. The patient should lie with the affected ear upward, and then the drops should be instilled. The tragus should then be pumped 4 times by pushing inward to facilitate penetration of the drops into the middle ear. This position should be maintained for five minutes. Repeat, if necessary, for the opposite ear.

Chronic Suppurative Otitis Media with perforated tympanic membranes:

The recommended dosage regimen for the treatment of chronic suppurative otitis media with perforated tympanic membranes in patients 12 years and older is:

Ten drops (0.5 mL, 1.5 mg ofloxacin) instilled into the affected ear twice daily for fourteen days. The solution should be warmed by holding the bottle in the hand for one or two minutes to avoid dizziness which may result from the instillation of a cold solution. The patient should lie with the affected ear upward, before instilling the drops. The tragus should then be pumped 4 times by pushing inward to facilitate penetration into the middle ear. This position should be maintained for five minutes. Repeat, if necessary, for the opposite ear.

Manufacturer

DIRECT RX

Active Ingredients

Source

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Clinical Trials [14 Associated Clinical Trials listed on BioPortfolio]

MSI-78 Topical Cream vs. Oral Ofloxacin in the Treatment of Infected Diabetic Ulcers

224 adults with diabetic foot ulcers will be randomized to either magainin peptide (MSI-78) or ofloxacin (FLOXIN, Ortho-McNeil Pharmaceutical Corporation) an oral fluoroquinolone antibioti...

A Double-Blind Study to Evaluate the Safety and Pharmacokinetics of L-Ofloxacin (RWJ 25213) in Subjects With HIV Infection

To determine the safety and pharmacokinetics of L-ofloxacin (RWJ 25213) in patients with HIV infection.

Protection From Cisplatin Ototoxicity by Lactated Ringers

The purpose of this study is to determine if Lactated Ringer's solution is effective in patients undergoing chemotherapy with cisplatin for head and neck cancer in regards to cisplatin-ind...

Treatment's Duration of Acute Uncomplicated Pyelonephritis

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Uncomplicated Pelvic Inflammatory Disease; Treatment With Moxifloxacin.

Comparison of various antibiotics in treatment of uncomplicated pelvic inflammatory disease

PubMed Articles [24 Associated PubMed Articles listed on BioPortfolio]

Heterogeneous fenton-like degradation of ofloxacin over sludge derived carbon as catalysts: Mechanism and performance.

In this study, heterogeneous Fenton-like degradation of ofloxacin (OFX) was investigated by sludge derived carbon (SC). The effects of SC catalyst, temperature and pH on the efficiency of ofloxacin de...

Degradation of antibiotics by modified vacuum-UV based processes: Mechanistic consequences of HO and KSO in the presence of halide ions.

In this work, the degradation of cefalexin, norfloxacin, and ofloxacin was examined via various advanced oxidation processes (AOPs). Direct photolysis by ultraviolet (UV) and vacuum ultra violet (VUV)...

Association of oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin with the risk of serious ventricular arrhythmia: a nationwide cohort study in Korea.

To evaluate whether oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin increase the risk of ventricular arrhythmia in Korea's general population.

The role of various transporters in the placental uptake of ofloxacin in an in vitro model of human villous trophoblasts.

Six years after the US Food and Drug Administration approval of the broad-spectrum antibiotic ofloxacin (OFLX), the chiral switching of this racemic mixture resulted in a drug composed of the L-optica...

Environmental contaminants in fish species from a large dam reservoir and their potential risks to human health.

The residue levels of antibiotics, metals and organochlorine pesticides (OCPs) were investigated in six fish species from the Karakaya Dam Reservoir, Turkey. Among monitored antibiotics, only enroflox...

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