OFLOXACIN- ofloxacin_solution

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 mcg/g after otic administration of a 0. Ofloxacin was present in high concentrations in otorrhea (389 - 2850 mcg/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 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 Aerobes, gram-positive: Staphylococcus aureus Streptococcus pneumoniae Aerobes, gram-negative: Escherichia coli Haemophilus influenzae Moraxella catarrhalis Proteus mirabilis Pseudomonas aeruginosa.
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 mcg/g after otic administration of a 0.3% solution. Ofloxacin was present in high concentrations in otorrhea (389 - 2850 mcg/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 Aerobes, gram-positive: Staphylococcus aureus Streptococcus pneumoniae Aerobes, gram-negative: 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 Escherichia coli Pseudomonas aeruginosa Staphylococcus aureus Chronic Suppurative Otitis Media Proteus mirabilis Pseudomonas aeruginosa Staphylococcus aureus Acute Otitis Media Haemophilus influenzae Moraxella catarrhalis Pseudomonas aeruginosa Staphylococcus aureus Streptococcus pneumoniae

Otitis Externa: 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: 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: 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.

ADVERSE REACTIONS
Subjects with Otitis Externa Incidence Rate Adverse Event Studies 002/003* Studies 016/017* Study 020* Application Site Reaction 3% 16. 6% Pruritus 4% 1. 0% Earache 1% 0. 8% Dizziness 1% 0. 6% Headache 0% 0. 2% Vertigo 1% 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 Earache Pruritus Paraesthesia Rash Dizziness 7% 1% 1% 1% 1% 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%), and 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. To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www. gov/medwatch.
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 Bausch & Lomb Incorporated at 1-800-553-5340 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

Pregnancy
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. 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.
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: ■ six months and older: otitis externa with intact 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.

Specific drug interaction studies have not been conducted with ofloxacin otic solution, 0.3%.

Store at 25ºC (77ºF); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). Protect from light.

WARNINGS
NOT FOR OPHTHALMIC USE. NOT FOR INJECTION.
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, 0.3% twice per day.
Patient Information
IMPORTANT PATIENT INFORMATION AND INSTRUCTIONS. READ BEFORE USE. What is ofloxacin otic solution, 0. 3%? Ofloxacin otic solution, 0. 3% is an antibiotic in a sterile solution used to treat ear infections caused by certain bacteria found in: ■ patients (12 years and older) who have a middle ear infection and have a hole in the eardrum Middle Ear Infection: Ear Canal Infection: Who should NOT use ofloxacin otic solution, 0. 3%? ■ Do not use this product if you are allergic to ofloxacin or to other quinolone antibiotics. ■ have an ear canal infection and are less than 6 months of age because no data were collected from this population ■ have a middle ear infection and have a tube in the eardrum and are less than one year of age because no data were collected from this population ■ have a middle ear infection and have a hole in the eardrum and are less than twelve years of age because no data were collected from this population How should ofloxacin otic solution, 0. 3% be given? 1. Wash hands The person giving ofloxacin otic solution, 0. 3% should wash his/her hands with soap and water. Clean ear and 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, 0. 3% in the hand for one or two minutes to warm the solution. Add drops For a Middle Ear Infection 10 drops 5 drops For an Ear Canal Infection (“Swimmer’s Ear”): The person receiving ofloxacin otic should lie on his/her side with the infected ear up. Patients (13 and older) should have 10 drops of ofloxacin otic put into the infected ear. Pediatric patients under 13 should have 5 drops put into the infected ear. The tip of the bottle should not touch the fingers or the ear or any other surfaces. 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”): While the person receiving the drops lies on his/her side, the person giving the drops should gently pull the outer ear upward and backward. This will allow the ear drops to flow down into the ear canal. 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 How often should ofloxacin otic solution, 0. 3% be given? In patients with an Ear Canal Infection (“Swimmer’s Ear”), ofloxacin otic 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, 0. 3% 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 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. What activities should be avoided while using ofloxacin otic solution, 0. 3%? It is important that the infected ear(s) remain clean and dry. When bathing, avoid getting the infected ear(s) wet. Avoid swimming unless the doctor has instructed otherwise. What are some of the possible side effects of ofloxacin otic solution, 0. 3%? During the testing of ofloxacin otic 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. During the testing of ofloxacin otic solution, 0. 3% 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 drops pass 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 about these or other side effects if they occur. If a rash or an allergic reaction to ofloxacin otic solution, 0. 3% occurs, stop using the product and contact your doctor. DO NOT TAKE ofloxacin otic solution, 0. 3% BY MOUTH. If ofloxacin otic solution, 0. 3% is accidentally 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, 0. 3% ask the doctor or pharmacist. See complete Prescribing Information. Storage: Distributed by: This Patient Information has been approved by the U. Food and Drug Administration. Revised 05/2023 hand ear drops pushear tragus sideear.

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