OFLOXACIN- ofloxaxin_solution/ drops

CLINICAL PHARMACOLOGY
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. 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. Ofloxacin has in vitro Ofloxacin has been shown to be active against most isolates of the following microorganisms, both in vitro INDICATIONS AND USAGE Staphylococcus aureus Streptococcus pneumoniae Aerobic and facultative gram-negative microorganisms Escherichia coli Proteus mirabilis Haemophilus influenzae Pseudomonas aeruginosa Moraxella catarrhalis.
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 Ofloxacin has been shown to be active against most isolates of the following microorganisms, both in vitro INDICATIONS AND USAGE Staphylococcus aureus Streptococcus pneumoniae Aerobic and facultative gram-negative microorganisms Escherichia coli Proteus mirabilis Haemophilus influenzae Pseudomonas aeruginosa Moraxella catarrhalis.

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 Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aereus Chronic Suppurative Otitis Media Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus Acute Otitis Media Haemophilus influenzae, Moraxella catarrhalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae
Otitis Externa
The recommended dosage regimen for the treatment of otitis externa is:
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:
What is Ofloxacin Otic Solution?
Ofloxacin Otic Solution is an antibiotic in a sterile solution used to treat ear infections caused by certain bacteria found in: Middle Ear Infection: Ear Canal Infection:

DOSAGE AND ADMINISTRATION
The recommended dosage regimen for the treatment of otitis externa is: The recommended dosage regimen for the treatment of acute otitis media in pediatric patients (from 1 to 12 years old) with tympanostomy tubes is: The recommended dosage regimen for the treatment of chronic suppurative otitis media with perforated tympanic membranes in patients 12 years and older is:.
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:
How should Ofloxacin Otic Solution be given?
Wash hands The person giving Ofloxacin Otic Solution should wash his/her hands with soap and water. Clean ear & warm bottle Gently clean any discharge that can be removed easily from the outer ear. DO NOT INSERT ANY OBJECT OR SWAB INTO THE EAR CANAL. Hold the bottle of Ofloxacin Otic Solution in the hand for one or two minutes to warm the solution. Add drops For a Middle Ear Infection 10 drops For an Ear Canal Infection (“Swimmer’s Ear”) 10 drops 5 drops BE SURE TO FOLLOW THE INSTRUCTIONS BELOW FOR THE PATIENT’S SPECIFIC EAR INFECTION. Press ear or pull ear For a Middle Ear Infection TRAGUS For an Ear Canal Infection (“Swimmer’s Ear”) 5. Stay on side The person who received the ear drops should remain on his/her side for at least 5 minutes. Repeat steps 2-5 for the other ear if both ears are infected. Step 1 Image Step 2 Image Step 3 Image Step 4 Image 1 Step 4 Image 2 Step 5 Image.
How often should Ofloxacin Otic Solution be given?
In patients with an Ear Canal Infection (“Swimmer’s Ear”), Ofloxacin Otic Solution ear drops should be given once daily at about the same time each day (for example, 8 AM or 8 PM) in each infected ear unless the doctor has instructed otherwise. In patients with a Middle Ear Infection, Ofloxacin Otic Solution ear drops should be given 2 times each day (about 12 hours apart, for example 8 AM and 8 PM) in each infected ear unless the doctor has instructed otherwise. The best times to use the ear drops are in the morning and at night. It is very important to use the ear drops for as long as the doctor has instructed, even if the symptoms improve

ADVERSE REACTIONS
To report SUSPECTED ADVERSE REACTIONS, contact Akorn Operating Company LLC at 1-800-932-5676 or FDA at 1-800-FDA-1088 or www. gov/medwatch. 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 dagger BID (N=229) Studies 016/017 dagger QD (N=310) Sudy 020 dagger QD (N=489) Application Site Reaction 3% 16. 6% Pruritis 4% 1. 0% Earache 1% 0. 8% Dizziness 1% 0. 6% Headache 0% 0. 2% Vertigo 1% 0. 0% dagger 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 sulfatehydrocortisone). 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. 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% Pruritis 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. 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. 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.
What are the possible side effects of Ofloxacin Otic Solution?
During the testing of Ofloxacin Otic Solution in external ear infections, the most common side effect was discomfort upon application which happened in 7% of patients. If the pain is severe, the medication should be stopped and you should contact your doctor. Other side effects were: itching (1%), earache (0.8%), and dizziness (0.4%). During the testing of Ofloxacin Otic Solution in middle ear infections, the most common side effect was a bitter taste which happened in 7% of patients with a middle ear infection. This may occur when some of the medication passes from the middle ear to the back of the mouth. This side effect is not serious and there is no need to stop the medicine if this should happen. Other side effects which were found in 1% of the patients were: earache, itching, abnormal sensation, rash and dizziness. Call your doctor for medical advice about side effects. You may report side effects to Akorn Operating Company LLC at 1-800-932-5676 or FDA at 1-800-FDA-1088. If a rash or an allergic reaction to Ofloxacin Otic Solution occurs, stop using the product and contact your doctor. DO NOT TAKE OFLOXACIN OTIC SOLUTION BY MOUTH. If Ofloxacin Otic Solution is accidently swallowed or overdose occurs, call the doctor immediately. This medicine is available only with a doctor’s prescription. Use only as directed. Do not use this medicine if outdated. If you wish to learn more about Ofloxacin Otic Solution ask the doctor or pharmacist.

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.
Who should NOT use Ofloxacin Otic Solution?
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Pregnancy
Pregnancy Category C. 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. 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 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 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.
Pediatric Use
Safety and efficacy have been demonstrated in pediatric patients of the following ages for the listed indications: Safety and efficacy in pediatric patients below these ages have not been established. Although no data are available on patients less than 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 ocurred 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.

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

WARNINGS
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.
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 micronucleus 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.
What if a dose is missed?
In patients with an Ear Canal Infection (“Swimmer’s Ear”), it is important that you take the drops every day. If you miss a dose which may have been scheduled for earlier in the day, (for example, 8 AM), you should take that day’s dose as soon as possible and then go back to your regular daily dosing schedule. In patients with Middle Ear Infection, if a dose of Ofloxacin Otic Solution is missed, it should be given as soon as possible. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Do not use a double dose unless the doctor has instructed you to do so. If the infection is not improved after one week, you should consult your doctor. If you have two or more episodes of drainage within six months, it is recommended that you see your doctor for further evaluation.

Akorn

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