Ofloxacin: Medical Uses, Adverse Effects, Contraindications, Interactions and Pharmacology

It is a useful antibiotic for treating a number of bacterial infections.

When taken by mouth or by injection into a vein, it treats pneumonia, cellulitis , urinary tract infections , prostatitis , plague, and certain types of infectious diarrhea.

In other uses, along with other medications, they include multidrug-resistant tuberculosis. An eye drop can be used for a superficial bacterial infection of the eye and an ear drop can be used for otitis media when there is a hole in the eardrum.

When taken by mouth, common side effects include vomiting, diarrhea, headache, and rash. Other serious side effects include tendon rupture, numbness due to nerve damage, seizures, and psychosis.

Use in pregnancy is generally not recommended. Ofloxacin belongs to the fluoroquinolone family of drugs. It works by interfering with the DNA of the bacteria.

Ofloxacin was patented in 1980 and approved for medical use in 1985. It is on the World Health Organization’s Essential Medicines List, the most effective and safest medicines needed in a health system.

Ofloxacin is available as a generic drug. The wholesale cost in the developing world is about $ 3.27 per month. In the United States, a course of treatment costs between $ 50 and $ 100.

Medical uses of ofloxacin

In the United States, ofloxacin is approved for the treatment of bacterial infections , such as:

  • Acute bacterial exacerbations of chronic bronchitis.
  • Community-acquired pneumonia.
  • Uncomplicated infections of the skin and skin structure.
  • Non-gonococcal urethritis and cervicitis.
  • Mixed infections of the urethra and cervix.
  • Acute pelvic inflammatory disease.
  • Uncomplicated cystitis.
  • Complicated urinary tract infections.
  • Prostatitis.
  • Acute, uncomplicated cervical and urethral gonorrhea.

Ofloxacin has not been shown to be effective in treating syphilis.

Bacteria susceptible al ofloxacino

According to the product package insert, ofloxacin is effective against the following microorganisms.

Aerobic gram-positive microorganisms:

  • Staphylococcus gold (methicillin-susceptible strains).
  • Streptococcus pneumoniae (penicillin-susceptible strains).
  • Estreptococo pyogenes.

Gram-negative aerobic microorganisms

  • Citrobacter koseri (Citrobacter diverse).
  • Enterobacter aerogenes.
  • Escherichia coli.
  • Haemophilus influenzae, formerly called Pfeiffer’s bacillus or Bacillus influenzae.
  • Klebsiella pneumonia.
  • Neisseria gonorrhoeae.
  • Proteus mirabilis.
  • Pseudomonas aeruginosa.

Other microorganisms:

  • Chlamydia trachomatis (clamidia).

Adverse effects

In general, fluoroquinolones are well tolerated, and most side effects are mild to moderate. Sometimes serious side effects occur. Common side effects include gastrointestinal effects such as nausea, vomiting, and diarrhea, as well as headache and insomnia.

The overall rate of adverse events in patients treated with fluoroquinolones is roughly similar to that seen in patients treated with other classes of antibiotics. A study by the US Centers for Disease Control.

It found that patients treated with fluoroquinolones experienced adverse events serious enough to lead to an emergency department visit more often than those treated with cephalosporins or macrolides, but less frequently than those treated with penicillins, clindamycin, sulfonamides, or vancomycin.

Post-marketing surveillance has revealed a variety of relatively rare but serious adverse effects that are associated with all members of the fluoroquinolone antibacterial class.

Among these, tendon problems and exacerbation of the symptoms of the neurological disorder myasthenia gravis are the subject of “black box” warnings in the United States.

The most severe form of tendonopathy associated with the administration of fluoroquinolones is tendon rupture, which in the vast majority of cases affects the Achilles tendon.

Younger people generally make a good recovery, but permanent disability is possible and more likely in older patients.

The overall frequency of fluoroquinolone-associated Achilles tendon rupture in patients treated with ciprofloxacin or levofloxacin has been estimated at 17 per 100,000 treatments.

The risk is substantially elevated in the elderly and in those with recent exposure to topical or systemic corticosteroid therapy. The simultaneous use of corticosteroids is present in almost a third of tendon rupture associated with quinolones.

Tendon damage can manifest during as well as up to a year after fluoroquinolone therapy has been completed. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels.

QT prolongation can lead to torsades de pointes, a life-threatening arrhythmia, but in practice this seems relatively uncommon, in part because the more widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval.

Diarrhea associated with the bacterium Clostridium difficile can occur in connection with the use of any antibacterial drug, especially those with a broad spectrum of activity such as clindamycin, cephalosporins, and fluoroquinolones.

Treatment with fluoroquinoline is associated with a risk similar to or lower than that associated with broad-spectrum cephalosporins. Administration of fluoroquinoline may be associated with the acquisition and growth of a particularly virulent strain of Clostridium.

The US prescribing information contains a warning about rare cases of peripheral neuropathy, which may be permanent.

Other nervous system effects include insomnia, restlessness, and rarely seizures, convulsions, and psychosis. Other rare and serious adverse events have been observed with varying degrees of evidence of causality.

Events that can occur in an acute overdose are rare and include kidney failure and seizures. Susceptible patient groups, such as children and the elderly, are at increased risk of adverse reactions during therapeutic use.

Ofloxacin, like some other fluoroquinolones, can inhibit the enzymes that metabolize drugs and therefore increase the blood levels of other drugs such as cyclosporine, theophylline, and warfarin, among others.

These increased blood levels can lead to an increased risk of side effects.

Careful monitoring of serum glucose is recommended when ofloxacin or other fluoroquinolones are used by people taking diabetes medications with sulfonylureas.

Concomitant administration of a non-steroidal anti-inflammatory drug with a quinolone, which includes ofloxacin, may increase the risk of CNS stimulation and seizures.

Fluoroquinolones have been shown to increase the anticoagulant effect of acenocoumarol, anisindione, and dicoumarol. In addition, there is an increased risk of cardiotoxicity and arrhythmias when co-administered with drugs such as dihydroquinidine barbiturate, quinidine, and quinidine barbiturate.

Current or past treatment with oral corticosteroids is associated with an increased risk of Achilles tendon rupture, especially in elderly patients who are also taking fluoroquinolones.

Contraindications of ofloxacin

As noted above, under licensed use, ofloxacin is now considered contraindicated for the treatment of certain sexually transmitted diseases by some experts due to bacterial resistance.

Caution in patients with liver disease

Ofloxacin excretion may be reduced in patients with severe liver function disorders (such as cirrhosis with or without ascites).

Ofloxacin is also considered contraindicated in the pediatric population, pregnancy, nursing mothers, patients with psychiatric illnesses, and in patients with epilepsy or other seizure disorders.

The pregnancy

Ofloxacin has not been shown to have a teratogenic effect at oral doses up to 810 mg / kg / day (11 times the maximum recommended human dose based on mg / m2 or 50 times based on mg / kg).

AND 160 mg / kg / day (4 times the maximum recommended human dose based on mg / m2 or 10 times based on mg / kg) when administered to pregnant rats and rabbits, respectively.

Additional studies in rats with oral doses up to 360 mg / kg / day (5 times the maximum recommended human dose based on mg / m2 or 23 times based on mg / kg) showed no adverse effects on late fetal development, parturition, delivery, lactation, neonatal viability or growth of the newborn.

Doses equivalent to 50 and 10 times the maximum recommended human dose of ofloxacin (on a mg / kg basis) were foetotoxic (i.e. decreased fetal body weight and increased fetal mortality) 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 the maximum recommended human dose based on mg / m2.

However, there are 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.

Interactions with other medications

Cimetidine can interfere with the elimination of some quinolones, including ofloxacin, although its interaction has not been studied.

Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with some other quinolones. The potential for interaction between ofloxacin and cyclosporine has not been studied.

Quinolones, including ofloxacin, can potentiate the effects of oral anticoagulants, including warfarin or its derivatives or similar agents.

Quinolones, including ofloxacin when given with glyburide, can rarely cause severe hypoglycemia.

Like other fluoroquinolones, ofloxacin inhibits CYP1A2 in vitro. When used with other drugs metabolized by CYP1A2 such as caffeine, clozapine, ropinirole, tacrine, theophylline, tizanidine, it can increase drug concentrations in the substrate when administered in normal doses.

Probenecid inhibits the renal excretion of ofloxacin and increases its levels.

Nonsteroidal anti-inflammatory drug (NSAID) and ofloxacin taken together may increase the risk of central nervous system stimulation and seizures.

Like multivitamins or other formulations containing iron or zinc, antacids, sucralfate, and didanosine chewable / buffered tablets or pediatric powder for oral solution interfere with the absorption of ofloxacin.

They should not be given concurrently with, or within 2 hours of, norfloxacin.

The use of fluoroquinolones, including ofloxacin, can cause an increase in plasma levels of theophylline when used simultaneously.

Kids

Oral and intravenous ofloxacin are not licensed for use in children, except as noted above, due to the risk of musculoskeletal injury.

In one study, 1534 young patients (6 months to 16 years) treated with levofloxacin as part of three efficacy trials were followed up to assess all musculoskeletal events that occurred up to 12 months after treatment.

At 12-month follow-up, the cumulative incidence of musculoskeletal adverse events was 3.4%, compared with 1.8% among 893 patients treated with other antibiotics.

In the levafloxacin-treated group, approximately two-thirds of these musculoskeletal adverse events occurred within the first 60 days, 86% were mild, 17% were moderate, and all resolved without long-term sequelae.

In a study comparing the safety and efficacy of levofloxacin with azithromycin or ceftriaxone in 712 children with community-acquired pneumonia, 6% of those treated with levofloxacin and 4% of those treated with comparative antibiotics experienced effects adverse.

Most of these adverse events were thought to be unrelated or doubtfully related to levofloxacin. Two deaths were observed in the levofloxacin group, neither of which were thought to be related to treatment.

Spontaneous reports to the Food and Drug Administration Adverse Effects Reporting System at the time of the Food and Drug Administration Pediatric Drug Advisory Committee on September 20, 2011 include musculoskeletal events.

Approximately 130,000 pediatric prescriptions for levofloxacin were filled on behalf of 112,000 pediatric patients during that period.

Overdose

There is limited information on ofloxacin overdose. Current advice for treating an acute ofloxacin overdose is to empty the stomach, along with close observation and adequate hydration of the patient.

Hemodialysis or peritoneal dialysis have limited effectiveness.

Overdose can cause central nervous system toxicity, cardiovascular toxicity, tendon / joint toxicity, and liver toxicity, as well as kidney failure and seizures. However, seizures have been reported to occur at a therapeutic dose and with severe psychiatric reactions.

Pharmacology of ofloxacin

The bioavailability of ofloxacin in tablet form is approximately 98% after oral administration reaching peak serum concentrations within one to two hours.

Between 65% and 80% of an administered oral dose of ofloxacin is excreted unchanged through the kidneys within 48 hours of administration. Therefore, elimination is mainly by renal excretion. However, four to eight percent of a dose of ofloxacin is excreted in the feces.

This would indicate a small degree of biliary excretion as well. The plasma elimination half-life is approximately 4 to 5 hours in patients and approximately 6.4 to 7.4 hours in elderly patients.

Ofloxacin is a racemic mixture, consisting of 50% levofloxacin (the biologically active component) and 50% of its “mirror image” or dextrofloxacin enantiomer.

Pharmacokinetics

Following multiple doses of 200 mg and 300 mg doses, peak serum levels of 2.2 μg / ml and 3.6 μg / ml, respectively, are predicted at steady state. In vitro, approximately 32% of the drug in plasma is protein bound.

The drug is widely distributed to body tissues. Ofloxacin has been detected in fluid from bullae, cervix, lung tissue, ovary, prostate fluid, prostate tissue, skin, and sputum.

The pyridobenzoxazine ring appears to decrease the extent of parent compound metabolism. Less than 5% is eliminated by the kidneys as desmethyl or N-oxide metabolites; 4% to 8% from faeces. ‘

There are several endogenous compounds that have been reported to be affected by ofloxacin as inhibitors, disruptors, and depletors. See the latest ofloxacin package insert for additional details.

Mode of action of ofloxacin

Ofloxacin is a broad-spectrum antibiotic that is active against Gram-positive and Gram-negative bacteria.

It works by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, which is an enzyme necessary to separate (mainly in prokaryotes, particularly bacteria) replicated DNA, thus inhibiting bacterial cell division.

History

Ofloxacin is a second generation fluoroquinolone, which is a broader spectrum norfloxacin analog, and was synthesized and developed by scientists at Daiichi Seiyaku.

It was first approved for marketing in Japan in 1985 for oral administration, and Daiichi marketed it there under the brand name Tarvid.

Daiichi, working with Johnson & Johnson, obtained Food and Drug Administration approval in December 1990 under the Floxin brand name.

Labeled for use in adults with lower respiratory tract infections, skin and skin structure infections, urinary tract infections, prostatitis, and sexually transmitted diseases.

In 1991 it was also marketed as Tarvid by Hoechst in the UK, Germany, Belgium and Portugal; such as Oflocet in France, Portugal, Tunisia and several African countries by Roussel-Uclafas, Oflocin by Glaxo in Italy and Flobacin by Sigma-Tau in Italy.

The market for olfoxacin was seen as difficult since its launch; it was approved as a ‘1C’ drug, a new molecular entity with little or no therapeutic gain over existing therapies, and the broader spectrum ciprofloxacin was already on the market.

In 1992, an IV solution was approved for commercialization. In 1997, the Food and Drug Administration approved an indication for pelvic inflammatory disease for the oral formulation, and in the same year, a solution for ear infections was approved under the brand name.

Daiichi and Johnson & Johnson also cannibalized their own market by introducing levofloxacin, the levoenantiomer of ofloxacin, in 1996.

Johnson and Johnson’s annual Floxin sales in 2003 were approximately $ 30 million, while their combined Levaquin Floxin sales exceeded $ 1.15 billion in the same year. Johnson & Johnson withdrew the marketing application in 2009.