Antibacterial

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 metabolities. 4% to 8% of an ofloxacin dose is excreted in the feces. This indicates a does not affect the C_max and AUC of the drug, but T_max is prolonged.

Following oral administration the bioavailability of ofloxacin in the tablet formulation is approximately 98%. Maximum serum concentrations are achieved 1-2 hours after an oral dose. Absorption of ofloxacin after single or multiple doses of 200-400 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 4-5 hours and 20-25 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 safety and effectiveness of the intravenous formulation in treating patients with severe infections have not been established.

In the absence of vomiting or other factors interfering with the absorption of orally administered drug, patients receive essentially the same systemic antimicrobial therapy after equivalent doses of ofloxacin administered by either the oral or the intravenous route. Therefore, the intravenous formulation does not provide a higher degree of efficacy or more potent antimicrobial activity than an equivalent dose of the oral formulation of ofloxacin.

Acute bacterial exacerbation of chronic bronchitis : Due to Haemophilus influenzae or streptococcus pneumoniae.

Uncomplicated skin and skin structure infections: Due to staphylococcus aureus, streptococcus pyrogens or Proteus mirabilis.

Acute Pelvic inflammatory disease : Due to Chlamydia trachomatis and Neisseria gonorrhoeae.

Uncomplicated cystitis : Due to citrobacter diversus, enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, proteus mirabilis or Pseudomonas aeruginosa.

Complicated urinary tract infections: Due to Escherichia coli, Klebsiella pneumoniae, proteus mirabilis, citrobacter diversus or pseudomonas aeruginosa.

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. Therapy with ofloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued.

Information on overdosage with ofloxacin is limited. One incident of accidental overdosage has been reported. In this case, an adult female received 3 grams of ofloxacin intravenously revealed an ofloxacin level of 39.4µg/ml. During the infusion, the patient developed drowsiness, nausea, dizziness, hot and moderate disorientation. All complaints except the dizziness subsided within 1 h after discontinuation of the infusion. The dizziness most bothersome while standing, resolved in approximately 9 h. Laboratory testing reportedly revealed no clinically significant changes in routine parameters in this patient.

In the event of an acute overdose, the patient should be observed and appropriate hydration maintained. Ofloxacin is not efficiency removed by hemodialysis or peritoneal dialysis.

The following is a complication of the data for ofloxacin based on clinical experience with both the oral and intravenous formulations. The incidence of drug-related adverse reactions in patients during phase 2 and 3 clinical trials was 11%. Among patients receiving multiple dose therapy, 4 % discontinued ofloxacin due to adverse experiences.

In clinical trials, the following events, regardless of relationship to drug, occurred in 1-3 %of patients: Abdominal pain and cramps, chest pain, decreased appetite, dry mouth, dysgeusia, fatigue, flatulence, gastrointestinal distress, nervousness, pharyngitis, pruritus, fever, rash, sleep disorders, somnolence, trunk pain, vaginal discharge, visual disturbances and constipation.

Body as a whole : Asthenia, chills, malaise, extremity pain, pain, epistaxis.

Urinary System : Dysuria, urinary frequency, urinary retention.

Cardiovascular System: Dysuria, urinary frequency, urinary retention.

Gastrointestinal system : Heaptic dysfunction including; hepatic necrosis, jaundice, hepatitis, intestinal perforation; pseudomembranous colitis (the onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment), GI hemorrhage; hiccough, painful oral mucosa, pyrosis.

Nervous system : Nightmares, suicidal thoughts or acts, disorientation, psychotic reactions, paranoia; phobia, agitation, restlessness, aggressiveness, manic reaction, emotional lability; peripheral neuropathy, ataxia, incordiantion; possible exacerbation of: myasthenia gravis and extrapyramidal disorders; dysphasia, light headedness.

Adequate hydration of patients receiving ofloxacin may result in hypotension. Ofloxacin injection should only be administered by slow intravenous infusion over a period of 60 minutes.

Ofloxacin had not been shown to have any teratogenic effects at oral doses as high as 810 mg/kg/day and 160 mg/kg/day when administerd to pregnant rats and rabbits, respectively. Additional studies in rats with oral doses up to 360 mg/kg/day demonstrated no adverse effect on late fetal development, labor, delivery, lactation, neonatal viability or growth of the newborn. Doses equivalent to 50 and 10 were fetotoxic in rats and rabbits, respectively. Minor skeletal variations were reported in rats receiving doses of 810 mg/kg/day which is more than 10 times higher than the recommended maximum human dose based on mg/m².

There are, however, no adequate and well-controlled studies in pregnant women. Ofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Ofloxacin is contra-indicated in persons with a history of hypersensitivity to ofloxacin, to other quinolones or to any of the omponents in this medication.

Keep in cool, dry place and protect from moisture and light. Store at a temperature of 25°C.