ofloxacin 200 MG Oral Tablet

INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of ofloxacin tablets, USP and other antibacterial drugs, ofloxacin tablets, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Ofloxacin tablets, USP are indicated for the treatment of adults with mild to moderate infections (unless otherwise indicated) caused by susceptible strains of the designated microorganisms in the infections listed below. Please see DOSAGE AND ADMINISTRATION for specific recommendations. Acute Bacterial Exacerbations of Chronic Bronchitis (ABECB) due to Haemophilus influenzae or Streptococcus pneumoniae . Because fluoroquinolones, including ofloxacin, have been associated with serious adverse reactions (see Warnings ), - and for some patients ABECB is self-limiting, reserve ofloxacin for treatment of ABECB in patients who have no alternative treatment options . Community-Acquired Pneumonia due to Haemophilus influenzae or Streptococcus pneumoniae . Uncomplicated Skin and Skin Structure Infections due to methicillin-susceptible Staphylococcus aureus, Streptococcus pyogenes, or Proteus mirabilis. Acute, Uncomplicated Urethral and Cervical Gonorrhea due to Neisseria gonorrhoeae (see WARNINGS ). Nongonococcal Urethritis and Cervicitis due to Chlamydia trachomatis (see WARNINGS ). Mixed Infections of the Urethra and Cervix due to Chlamydia trachomatis and Neisseria gonorrhoeae (see WARNINGS ). Acute Pelvic Inflammatory Disease (including severe infection) due to Chlamydia trachomatis and/or Neisseria gonorrhoeae (see WARNINGS ). NOTE: If anaerobic microorganisms are suspected of contributing to the infection, appropriate therapy for anaerobic pathogens should be administered. Uncomplicated Cystitis due to Citrobacter diversus, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa. Because fluoroquinolones, including ofloxacin, have been associated with serious adverse reactions (see WARNINGS ), and for some patients uncomplicated cystitis is self-limiting, reserve ofloxacin for treatment of uncomplicated cystitis in patients who have no alternative treatment options. Complicated Urinary Tract Infections due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter diversus,* or Pseudomonas aeruginosa.* Prostatitis due to Escherichia coli. * = Although treatment of infections due to this organism in this organ system demonstrated a clinically significant outcome, efficacy was studied in fewer than 10 patients. Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to ofloxacin, USP. Therapy with ofloxacin, USP may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued. As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with ofloxacin, USP. Culture and susceptibility testing performed periodically during therapy will provide information not only on the therapeutic effect of the antimicrobial agent but also on the possible emergence of bacterial resistance.

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.

WARNINGS Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects Fluoroquinolones, including ofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting ofloxacin. Patients of any age or without pre-existing risk factors have experienced these adverse reactions (see Warnings ) Discontinue ofloxacin immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including ofloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones. Tendinitis and Tendon Rupture Fluoroquinolones, including ofloxacin, have been associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon and has been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur within hours or days of starting ofloxacin, or as long as several months after completion of fluoroquinolone therapy. Tendinitis and tendon rupture can occur bilaterally. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have been reported in patients taking fluoroquinolones who do not have the above risk factors. Discontinue ofloxacin immediately if the patient experiences pain, swelling, inflammation or rupture of a tendon. Avoid fluoroquinolones, including ofloxacin, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture (see Adverse Reactions ). Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug. Peripheral Neuropathy Fluoroquinolones, including ofloxacin, have been associated with an increased risk of peripheral neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones, including ofloxacin. Symptoms may occur soon after initiation of norfloxacin and may be irreversible in some patients (see WARNINGS ). Discontinue ofloxacin immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness, or other alterations in sensations including light touch, pain, temperature, position sense and vibratory sensation, and/or motor strength in order to minimize the development of an irreversible condition. Avoid fluoroquinolones, including ofloxacin, in patients who have previously experienced peripheral neuropathy (see Adverse Reactions ) Central Nervous System Effects Psychiatric Adverse Reactions Fluoroquinolones, including ofloxacin, have been associated with an increased risk of psychiatric adverse reactions toxic psychoses or hallucinations; agitation; delirium, confusion, disorientation, or disturbances in attention; nervousness or restlessness, memory impairment. If these reactions occur in patients receiving ofloxacin, the drug should be discontinued and appropriate measures instituted. Central Nervous System Adverse Reactions Fluoroquinolones have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (pseudotumor cerebri), lightheadedness, or tremors. The effects of ofloxacin on brain function or on the electrical activity of the brain have not been tested. Therefore, until more information becomes available, ofloxacin, like all other quinolones, should be used with caution in patients with known or suspected CNS disorders, such as severe cerebral arteriosclerosis, epilepsy, and other factors which predispose to seizures (see ADVERSE REACTIONS ). Exacerbation of Myasthenia Gravis Fluoroquinolones, including ofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid ofloxacin in patients with known history of myasthenia gravis (see PRECAUTIONS, Information for Patients and ADVERSE REACTIONS, Postmarketing Adverse Events ). THE SAFETY AND EFFICACY OF OFLOXACIN IN PEDIATRIC PATIENTS AND ADOLESCENTS (UNDER THE AGE OF 18 YEARS), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED (see PRECAUTIONS, Pediatric Use , Pregnancy , and Nursing Mothers Subsections). In the immature rat, the oral administration of ofloxacin at 5 to 16 times the recommended maximum human dose based on mg/kg or 1 to 3 times based on mg/m 2 increased the incidence and severity of osteochondrosis. The lesions did not regress after 13 weeks of drug withdrawal. Other quinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species ( see ANIMAL PHARMACOLOGY ). Hypersensitivity Reactions Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with quinolones, including ofloxacin. These reactions often occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions. This drug should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated (see PRECAUTIONS and ADVERSE REACTIONS ). Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including ofloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following: fever, rash, or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis; arthralgia; myalgia; serum sickness; allergic pneumonitis; interstitial nephritis; acute renal insufficiency or failure; hepatitis; jaundice; acute hepatic necrosis or failure; anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities. The drug should be discontinued immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted (see PRECAUTIONS, Informatio

CONTRAINDICATIONS Ofloxacin Ophthalmic Solution is contraindicated in patients with a history of hypersensitivity to ofloxacin, to other quinolones, or to any of the components in this medication ( see WARNINGS ) .

CLINICAL PHARMACOLOGY Following oral administration, the bioavailability of ofloxacin in the tablet formulation is approximately 98%. Maximum serum concentrations are achieved one to two hours after an oral dose. Absorption of ofloxacin after single or multiple doses of 200 to 400 mg is predictable, and the amount of drug absorbed increases proportionately with the dose. Ofloxacin has biphasic elimination. Following multiple oral doses at steady-state administration, the half-lives are approximately 4 to 5 hours and 20 to 25 hours. However, the longer half-life represents less than 5% of the total AUC. Accumulation at steady-state can be estimated using a half-life of 9 hours. The total clearance and volume of distribution are approximately similar after single or multiple doses. Elimination is mainly by renal excretion. The following are mean peak serum concentrations in healthy 70 to 80 kg male volunteers after single oral doses of 200, 300, or 400 mg of ofloxacin or after multiple oral doses of 400 mg. Oral Dose Serum Concentration 2 Hours After Admin. (mcg/mL) Area Under the Curve (AUC (0 to ∞) ) (mcg∙h/mL) 200 mg single dose 1.5 14.1 300 mg single dose 2.4 21.2 400 mg single dose 2.9 31.4 400 mg steady-state 4.6 61.0 Steady-state concentrations were attained after four oral doses, and the area under the curve (AUC) was approximately 40% higher than the AUC after single doses. Therefore, after multiple-dose administration of 200 mg and 300 mg doses, peak serum levels of 2.2 mcg/mL and 3.6 mcg/mL, respectively, are predicted at steady-state. In vitro , approximately 32% of the drug in plasma is protein bound. The single dose and steady-state plasma profiles of ofloxacin injection were comparable in extent of exposure (AUC) to those of ofloxacin tablets when the injectable and tablet formulations of ofloxacin were administered in equal doses (mg/mg) to the same group of subjects. The mean steady-state AUC (0 to 12) attained after the intravenous administration of 400 mg over 60 min was 43.5 mcg∙h/mL; the mean steady-state AUC (0 to 12) attained after the oral administration of 400 mg was 41.2 mcg∙h/mL (two one-sided t-test, 90% confidence interval was 103 to 109) (see following chart). Between 0 and 6 h following the administration of a single 200 mg oral dose of ofloxacin to 12 healthy volunteers, the average urine ofloxacin concentration was approximately 220 mcg/mL. Between 12 and 24 hours after administration, the average urine ofloxacin level was approximately 34 mcg/mL. Following oral administration of recommended therapeutic doses, ofloxacin has been detected in blister fluid, cervix, lung tissue, ovary, prostatic fluid, prostatic tissue, skin, and sputum. The mean concentration of ofloxacin in each of these various body fluids and tissues after one or more doses was 0.8 to 1.5 times the concurrent plasma level. Inadequate data are presently available on the distribution or levels of ofloxacin in the cerebrospinal fluid or brain tissue. Ofloxacin has a pyridobenzoxazine ring that appears to decrease the extent of parent compound metabolism. Between 65% and 80% of an administered oral dose of ofloxacin is excreted unchanged via the kidneys within 48 hours of dosing. Studies indicate that less than 5% of an administered dose is recovered in the urine as the desmethyl or N-oxide metabolites. Four to eight percent of an ofloxacin dose is excreted in the feces. This indicates a small degree of biliary excretion of ofloxacin. The administration of ofloxacin tablets with food does not affect the C max and AUC ∞ of the drug, but T max is prolonged. Clearance of ofloxacin is reduced in patients with impaired renal function (creatinine clearance rate ≤50 mL/min), and dosage adjustment is necessary (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION ). Following oral administration to healthy elderly subjects (65 to 81 years of age), maximum plasma concentrations are usually achieved one to two hours after single and multiple twice-daily doses, indicating that the rate of oral absorption is unaffected by age or gender. Mean peak plasma concentrations in elderly subjects were 9 to 21% higher than those observed in younger subjects. Gender differences in the pharmacokinetic properties of elderly subjects have been observed. Peak plasma concentrations were 114% and 54% higher in elderly females compared to elderly males following single and multiple twice-daily doses. [This interpretation was based on study results collected from two separate studies.] Plasma concentrations increase dose-dependently with the increase in doses after single oral dose and at steady state. No differences were observed in the volume of distribution values between elderly and younger subjects. As in younger subjects, elimination is mainly by renal excretion as unchanged drug in elderly subjects, although less drug is recovered from renal excretion in elderly subjects. Consistent with younger subjects, less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites in the elderly. A longer plasma half-life of approximately 6.4 to 7.4 hours was observed in elderly subjects, compared with 4 to 5 hours for young subjects. Slower elimination of ofloxacin is observed in elderly subjects as compared with younger subjects which may be attributable to the reduced renal function and renal clearance observed in the elderly subjects. Because ofloxacin is known to be substantially excreted by the kidney, and elderly patients are more likely to have decreased renal function, dosage adjustment is necessary for elderly patients with impaired renal function as recommended for all patients. (see PRECAUTIONS, General and DOSAGE AND ADMINISTRATION ). Figure MICROBIOLOGY Ofloxacin is a quinolone antimicrobial agent. The mechanism of action of ofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination. Ofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. Ofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations. Fluoroquinolones, including ofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides and β -lactam antibiotics, including penicillins. Fluoroquinolones may, therefore, be active against bacteria resistant to these antimicrobials. Resistance to ofloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10 -9 to 10 -11 ). Although cross-resistance has been observed between ofloxacin and some other fluoroquinolones, some microorganisms resistant to other fluoroquinolones may be susceptible to ofloxacin. Ofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section: Aerobic Gram-Positive Microorganisms Staphylococcus aureus (methicillin-susceptible strains) Streptococcus pneumoniae (penicillin-susceptible strains) Streptococcus pyogenes Aerobic Gram-Negative Microorganisms Citrobacter (diversus) koseri Enterobacter aerogenes Escherichia coli Haemophilus influenzae Klebsiella pneumoniae Neisseria gonorrhoeae Proteus mirabilis Pseudomonas aeruginosa As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with ofloxacin. Other Microorganisms Chlamydia trachomatis The following in vitro data are available, but their clinical significance is unknown . Ofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 mcg/mL or less against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of ofloxacin in treating clinical infections due to these microorganisms have not been establish