Ofloxacin Otic

INDICATIONS AND USAGE 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 .

DOSAGE AND ADMINISTRATION 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 one 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 that 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 that 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.

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.

CONTRAINDICATIONS Ofloxacin otic solution 0.3% is contraindicated in patients with a history of hypersensitivity to ofloxacin, to other quinolones, or to any of the components in this medication.

ADVERSE REACTIONS 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 Studies 002/003 (BID) and 016/017 (QD) were active-controlled and comparative. Study 020 (QD) was open and non-comparative. BID (N=229) Studies 016/017 QD (N=3109) 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% 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 neurospsychiatric disturbances have been included in spontaneous post-marketing reports. A causal relationship with ofloxacin otic solution 0.3% is unknown.

Drug Interactions Specific drug interaction studies have not been conducted with ofloxacin otic solution.

DESCRIPTION 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 carboxy-quinolone with a benzoxazine ring. The chemical name of ofloxacin is: (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7 H -pyrido[1,2,3- de ]-1,4-benzoxazine-6-carboxylic acid. The empirical formula of ofloxacin is C 18 H 20 FN 3 O 4 and its molecular weight is 361.38. The structural formula is: Ofloxacin Otic Solution contains 0.3% (3 mg/mL) ofloxacin with benzalkonium chloride (0.0025%), hydrochloric acid, sodium chloride, and water for injection. Additional hydrochloric acid and/or sodium hydroxide may be added to adjust the pH (6.5 ± 0.5). structure

HOW SUPPLIED Ofloxacin Otic Solution 0.3% is supplied in bottles containing 5 mL NDC 63187-184-05 Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature]. Manufactured by: Manufactured for: Relabeled by: Apotex Inc. Apotex Corp. Proficient Rx LP Toronto, Ontario Weston, Florida 33326 Thousand Oaks, CA 91320 Canada M9L 1T9 247807 January 2007