Ofloxacin


Ofloxacin is a quinolone antibiotic useful for the treatment of a number of bacterial infections. When taken by mouth or injection into a vein, these include pneumonia, cellulitis, urinary tract infections, prostatitis, plague, and certain types of infectious diarrhea. Other uses, along with other medications, include treating multidrug resistant tuberculosis. An eye drop may be used for a superficial bacterial infection of the eye and an ear drop may be used for otitis media when a hole in the ear drum is present.
When taken by mouth, common side effects include vomiting, diarrhea, headache, and rash. Other serious side effect include tendon rupture, numbness due to nerve damage, seizures, and psychosis. Use in pregnancy is typically not recommended. Ofloxacin is in the fluoroquinolone family of medications. It works by interfering with the bacterium's DNA.
Ofloxacin was patented in 1980 and approved for medical use in 1985. It is on the World Health Organization's List of Essential Medicines. Ofloxacin is available as a generic medication. In 2023, it was the 169th most commonly prescribed medication in the United States, with more than 2million prescriptions.

Medical uses

Ofloxacin is used in the treatment of bacterial infections such as:
Ofloxacin has not been shown to be effective in the treatment of syphilis.
Fluoroquinolones, the class of drug ofloxacin belongs to, were the drug of choice for treating gonorrhea in the 1980s; However, due to the development of fluoroquinolone-resistant Neisseria gonorrhoeae, fluoroquinolones were no longer used to treat gonorrhea by the late 1990s. As of 2004, the failure of single dose ofloxacin to treat gonorrhea has been reported in the United States, United Kingdom, Canada, and Australia.

Susceptible bacteria

According to the product package insert, ofloxacin is effective against these microorganisms:
Aerobic Gram-positive microorganisms:
  • Staphylococcus aureus
  • Streptococcus pneumoniae
  • Streptococcus pyogenes
Aerobic Gram-negative microorganisms
  • Citrobacter koseri
  • Enterobacter aerogenes
  • Escherichia coli
  • Haemophilus influenzae
  • Klebsiella pneumoniae
  • Neisseria gonorrhoeae
  • Proteus mirabilis
  • Pseudomonas aeruginosa
Other microorganisms:
  • ''Chlamydia trachomatis''

    Adverse effects

In general, fluoroquinolones are well tolerated, with most side effects being mild to moderate. On occasion, serious adverse 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 antibiotic classes. A U.S. Centers for Disease Control study found patients treated with fluoroquinolones experienced adverse events severe enough to lead to an emergency department visit more frequently than those treated with cephalosporins or macrolides, but less frequently than those treated with penicillins, clindamycin, sulfonamides, or vancomycin.
Postmarketing surveillance has revealed a variety of relatively rare but serious adverse effects 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 fluoroquinolone administration is tendon rupture, which in the great majority of cases involves the Achilles tendon. Younger people typically experience good recovery, but permanent disability is possible, and is 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. Risk is substantially elevated in the elderly and in those with recent exposure to topical or systemic corticosteroid therapy. Simultaneous use of corticosteroids is present in almost one-third of quinolone-associated tendon rupture. Tendon damage may manifest during and up to a year after fluoroquinolone therapy has been completed.
Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels. Prolongation of the QT interval can lead to torsades de pointes, a life-threatening arrhythmia, but in practice, this appears relatively uncommon in part because the most widely prescribed fluoroquinolones only minimally prolong the QT interval.
Clostridioides difficile-associated diarrhea may occur in connection with the use of any antibacterial drug, especially those with a broad spectrum of activity such as clindamycin, cephalosporins, and fluoroquinolones. Fluoroquinoline treatment is associated with risk similar to or less than that associated with broad spectrum cephalosporins. Fluoroquinolone administration may be associated with the acquisition and outgrowth of a particularly virulent Clostridium strain.
The US prescribing information contains a warning regarding uncommon cases of peripheral neuropathy, which can be permanent. Other nervous system effects include insomnia, restlessness, and rarely, seizure, convulsions, and psychosis Other rare and serious adverse events have been observed with varying degrees of evidence for causation.
Events that may occur in acute overdose are rare, and include kidney failure and seizure. Susceptible groups of patients, such as children and the elderly, are at greater risk of adverse reactions during therapeutic use.
Ofloxacin, like some other fluoroquinolones, may inhibit drug-metabolizing enzymes, and thereby increase blood levels of other drugs such as cyclosporine, theophylline, and warfarin, among others. These increased blood levels may result in a greater risk of side effects.
Careful monitoring of serum glucose is advised when ofloxacin or other fluorquinolones are used by people who are taking sulfonylurea antidiabetes drugs.
The concomitant administration of a nonsteroidal anti-inflammatory drug with a quinolone, including ofloxacin, may increase the risk of central nervous system stimulation and convulsive seizures.
The fluoroquinolones have been shown to increase the anticoagulant effect of acenocoumarol, anisindione, and dicumarol. Additionally, the risk of cardiotoxicity and arrhythmias is increased 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 the fluoroquinolones.

Contraindications

As noted above, under licensed use, ofloxacin is now considered to be contraindicated for the treatment of certain sexually transmitted diseases by some experts due to bacterial resistance. Caution should be used in people with liver disease. The excretion of ofloxacin may be reduced in patients with severe liver function disorders. Ofloxacin is also considered to be contraindicated within the pediatric population, pregnancy, nursing mothers, patients with psychiatric illnesses and in patients with epilepsy or other seizure disorders.

Pregnancy

Ofloxacin has not been shown to have any teratogenic effects at oral doses as high as 810 mg/kg/day and 160 mg/kg/day when administered 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 times the recommended maximum human dose of ofloxacin 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.

Children

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 juvenile patients treated with levofloxacin as part of three efficacy trials were followed up to assess all musculoskeletal events occurring up to 12 months after treatment. At 12 months' follow-up, the cumulative incidence of musculoskeletal adverse events was 3.4%, compared to 1.8% among 893 patients treated with other antibiotics. In the levafloxacin-treated group, about two-thirds of these musculoskeletal adverse events occurred in 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 to that of azithromycin or ceftriaxone in 712 children with community-acquired pneumonia, adverse events were experienced by 6% of those treated with levofloxacin and 4% of those treated with comparator antibiotics. Most of these adverse events were thought to be unrelated or doubtfully related to the levofloxacin. Two deaths were observed in the levofloxacin group, neither of which was thought to be treatment-related. Spontaneous reports to the FDA Adverse Effects Reporting System at the time of the 20 September 2011 FDA Pediatric Drugs Advisory Committee include musculoskeletal events and central nervous system events as the most common spontaneous reports between April 2005 and March 2008. An estimated 130,000 pediatric prescriptions for levofloxacin were filled on behalf of 112,000 pediatric patients during that period.