Ofloxacin Otic

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 .

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.

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.

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: Adverse Event Incidence Rate Studies 002/003† BID (N=229) Studies 016/017† QD (N=310) Study 020† 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. To report SUSPECTED ADVERSE REACTIONS, contact Lifestar Pharma LLC at 1-888-995-4337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Specific drug interaction studies have not been conducted with Ofloxacin Otic Solution 0.3%.

Teratogenic effects: Ofloxacin has been shown to have an embryocidal effect in rats at a dose of 810 mg/kg/day and in rabbits at 160 mg/kg/day. These dosages resulted in decreased fetal body weights 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. Ofloxacin has not been shown to have any adverse effects on the developing embryo or fetus at doses relevant to the amount of ofloxacin that will be delivered ototopically at the recommended clinical doses. Nonteratogenic Effects: Additional studies in the rat demonstrated that doses up to 360 mg/kg/day during late gestation had no adverse effects 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 Otic Solution 0.3% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 otic 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.

Safety and efficacy have been demonstrated in pediatric patients of the following ages for the listed indications:

• six months and older: otitis externa with intact tympanic membranes
• one year and older: acute otitis media with tympanostomy tubes
• twelve years and older: chronic suppurative otitis media with perforated tympanic membranes Safety and efficacy in pediatric patients below these ages have not been established. Although no data are available on patients less than age 6 months, there are no known safety concerns or differences in the disease process in this population that will preclude use of this product. No changes in hearing function occurred in 30 pediatric subjects treated with ofloxacin otic and tested for audiometric parameters. Although quinolones, including ofloxacin, have been shown to cause arthropathy in immature animals after systemic administration, young growing guinea pigs dosed in the middle ear with 0.3% Ofloxacin Otic Solution for one month showed no systemic effects, quinolone-induced lesions, erosions of the cartilage in weight-bearing joints, or other signs of arthropathy.