Ofloxacin
Clinical data | |
---|---|
Trade names | Floxin, Ocuflox, others |
Other names | (±)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid |
AHFS/Drugs.com | Monograph |
MedlinePlus | a691005 |
License data | |
ATC code | |
Legal status | |
Legal status |
|
Pharmacokinetic data | |
Bioavailability | 85% – 95% |
Protein binding | 32% |
Elimination half-life | 8–9 hours |
Identifiers | |
| |
JSmol) | |
Chirality | Racemic mixture |
Melting point | 250–257 °C (482–495 °F) |
| |
| |
(verify) |
Ofloxacin is a
When taken by mouth, common side effects include vomiting, diarrhea, headache, and rash.
Ofloxacin was patented in 1980 and approved for medical use in 1985.
Medical uses
Ofloxacin is used in the treatment of bacterial infections such as:
- Acute bacterial exacerbations of chronic obstructive pulmonary disease (COPD)
- Community-acquired pneumonia
- Uncomplicated skin and skin structure infections
- Nongonococcal urethritis and cervicitis
- Epididymitis
- Mixed Infections of the urethra and cervix
- Acute pelvic inflammatory disease
- Uncomplicated cystitis
- Complicated urinary tract infections
- Prostatitis
- Acute, uncomplicated urethral and cervical gonorrhea
Ofloxacin has not been shown to be effective in the treatment of syphilis.[9]
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.[10] As of 2004, the failure of single dose ofloxacin to treat gonorrhea has been reported in the United States, United Kingdom, Canada, and Australia. [11]
Susceptible bacteria
According to the product package insert, ofloxacin is effective against these microorganisms:[12]
Aerobic Gram-positive microorganisms:
- Staphylococcus aureus (methicillin-susceptible strains)
- Streptococcus pneumoniae (penicillin-susceptible strains)
- Streptococcus pyogenes
Aerobic Gram-negative microorganisms
- Citrobacter koseri (Citrobacter diversus)
- Enterobacter aerogenes
- Escherichia coli
- Haemophilus influenzae
- Klebsiella pneumoniae
- Neisseria gonorrhoeae
- Proteus mirabilis
- Pseudomonas aeruginosa
Other microorganisms:
Adverse effects
In general, fluoroquinolones are well tolerated, with most side effects being mild to moderate.[13] On occasion, serious adverse effects occur.[14] 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.[15][16][17][18] 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.[19]
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
Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels.[25] 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 (ciprofloxacin and levofloxacin) only minimally prolong the QT interval.[26]
Clostridium 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[27] or less[28][29] than that associated with broad spectrum cephalosporins. Fluoroquinoline administration may be associated with the acquisition and outgrowth of a particularly virulent Clostridium strain.[30]
The US prescribing information contains a warning regarding uncommon cases of peripheral neuropathy, which can be permanent.[31] Other nervous system effects include insomnia, restlessness, and rarely, seizure, convulsions, and psychosis[32] Other rare and serious adverse events have been observed with varying degrees of evidence for causation.[33][34][35][36]
Events that may occur in acute overdose are rare, and include kidney failure and seizure.[37] Susceptible groups of patients, such as children and the elderly, are at greater risk of adverse reactions during therapeutic use.[13][38][39]
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
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.[41]
Contraindications
As noted above, under licensed use, ofloxacin is now considered to be
Pregnancy
Ofloxacin has not been shown to have any teratogenic effects at oral doses as high as 810 mg/kg/day (11 times the recommended maximum human dose based on mg/m2 or 50 times based on mg/kg) and 160 mg/kg/day (four times the recommended maximum 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 (five times the recommended maximum human dose based on mg/m2 or 23 times based on mg/kg) 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 (based on mg/kg) were fetotoxic (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 higher than the recommended maximum human dose based on mg/m2.[44][45]
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.[9]
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,[46][47] 1534 juvenile patients (age 6 months to 16 years) 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 (39, including five cases of tendon rupture) and central nervous system events (19, including five cases of seizures) 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.[48]
Overdose
Limited information is available on overdose with ofloxacin. Advice for the management of an acute overdose of ofloxacin is emptying of the stomach, along with close observation, and making sure that the patient is appropriately hydrated. Hemodialysis or peritoneal dialysis is of only limited effectiveness.
Pharmacokinetics
The
Ofloxacin is a
"After multiple-dose administration of 200 mg and 300 mg doses, peak serum levels of 2.2 and 3.6 μg/ml, respectively, are predicted at steady-state. In vitro, approximately 32% of the drug in plasma is protein bound. Floxin is widely distributed to body tissues. Ofloxacin has been detected in blister fluid, cervix, lung tissue, ovary, prostatic fluid, prostatic tissue, skin, and sputum. 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% by feces."[9][53]
A number of the endogenous compounds have been reported to be affected by ofloxacin as inhibitors, alteraters, and depletors. See the latest package insert for ofloxacin for additional details.[9]
Mode of action
Ofloxacin is a
History
Ofloxacin is a second-generation fluoroquinolone, being a broader-spectrum analog of norfloxacin, and was synthesized and developed by scientists at Daiichi Seiyaku.[55][56]
It was first approved for marketing in Japan in 1985, for oral administration, and Daiichi marketed it there under the brand name Tarvid.[57] Daiichi, working with Johnson & Johnson, obtained FDA approval in December 1990, under the brand name Floxin, labelled for use in adults with lower respiratory tract infections, skin and skin structure infections, urinary tract infections, prostatitis, and sexually transmitted diseases.[58][59] By 1991, it was also marketed as Tarvid by Hoechst in the UK, Germany, Belgium, and Portugal; as Oflocet in France, Portugal, Tunisia, and several African countries by Roussel-Uclaf, as Oflocin by Glaxo in Italy, and as Flobacin by Sigma-Tau in Italy.[56]
The market for ofloxacin was seen as difficult from its launch; it was approved as a "1C" drug, a new molecular entity with little or no therapeutic gain over existing therapies, and ciprofloxacin, which had a broader spectrum, was already on the market.[59]
By 1992, an intravenous solution was approved for marketing,[60]
In 1997, an indication for pelvic inflammatory disease was approved by the U.S. Food and Drug Administration (FDA) for the oral formulation,[61] and in the same year, a solution for ear infections was approved under the brand [62]
Daiichi and J&J also cannibalized its own market by introducing levofloxacin, the levo-enantiomer of ofloxacin, in 1996;[57] Johnson and Johnson's annual sales of Floxin in 2003 was about $30 million, whereas their combined sales of Levaquin/Floxin exceeded $1.15 billion in the same year.[63][64] Johnson & Johnson withdrew the marketing application in 2009.[65]
Society and culture
Available forms
Ofloxacin for systemic use is available in multiple strengths as a tablet, an oral suspension, and an injectable solution. It is also used as eye drops and ear drops and is available in combination with ornidazole.[66]
Antibiotic use and bacterial resistance
Floxacin and other fluoroquinolones had become the most commonly prescribed class of antibiotics to adults in 2002. Nearly half (42%) of these prescriptions were for conditions not approved by the U.S. Food and Drug Administration (FDA), such as acute bronchitis, otitis media, and acute upper respiratory tract infection.[68] Additionally they are commonly prescribed for medical conditions that are not even bacterial to begin with, such as viral infections, or those to which no proven benefit exists.
References
- ^ a b c d e f g "Ofloxacin". The American Society of Health-System Pharmacists. Archived from the original on 28 December 2016. Retrieved 8 December 2016.
- ^ ISBN 9780857111562.
- ISBN 9789241547659.
- ^ "Ofloxacin Use During Pregnancy | Drugs.com". www.drugs.com. Archived from the original on 28 December 2016. Retrieved 28 December 2016.
- ISBN 9783527607495. Archivedfrom the original on 2016-12-29.
- hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
- ^ "Ofloxacin - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
- ^ a b c d e f "Ofloxacin tablet, film coated". DailyMed. 4 September 2019. Retrieved 6 January 2020.
- S2CID 255433752.
- S2CID 1706114.
- PMID 6960805.
- ^ PMID 15942881.
- PMID 11172695.
- ^ "Data Mining Analysis of Multiple Antibiotics in AERS". U.S. Food and Drug Administration (FDA). Archived from the original on 2016-03-10.
- PMID 22489673.
- PMID 17165634.
- S2CID 19026852.
- PMID 18694344.
- PMID 20725547.
- S2CID 3330687.
- PMID 15942881.
- PMID 16139623.
- PMID 10970974.
- PMID 23570031.
- PMID 11909831.
- PMID 23620467.
- PMID 24324224.
- ^ "Data Mining Analysis of Multiple Antibiotics in AERS". Food and Drug Administration. Archived from the original on 2016-03-10.
- PMID 22921930.
- ^ "FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection". U.S. Food and Drug Administration (FDA). Archived from the original on 2016-05-28.
- PMID 15661570.
- S2CID 36759747.
- PMID 16876974.
- S2CID 26411679.
- PMID 9093098.
- ^ ISBN 978-0-07-143763-9. Archivedfrom the original on 2014-06-12.
- S2CID 34091286.
- ^ Farinas ER (1 March 2005). "Consult: One-Year Post Pediatric Exclusivity Postmarketing Adverse Events Review" (PDF). Public Health Service Food and Drug Administration Center for Drug Evaluation and Research. U.S. Food and Drug Administration (FDA). Archived from the original (PDF) on 21 October 2009. Retrieved 31 August 2009.
- ^ "Showing drug card for Ofloxacin (DB01165)". Canada: DrugBank. February 19, 2009. Archived from the original on May 14, 2016.
- PMID 12912715.
- ^ Blank S, Schillinger J (May 14, 2004). "DOHMH ALERT #8:Fluoroquinolone-resistant gonorrhea, NYC". USA: New York County Medical Society. Archived from the original on July 22, 2011. Retrieved July 22, 2009.
- S2CID 26688176.
- ISSN 0277-0008Volume: 25 | Issue: 1 Cover date: January 2005 Page(s): 116–118
- PMID 12700435.
- ^ "Levaquin- levofloxacin tablet, film coated". DailyMed. 12 July 2019. Retrieved 6 January 2020.
- S2CID 26457648.
- ^ "Adverse Event Review: Levaquin (levofloxacin)" (PDF). U.S. Food and Drug Administration (FDA). Archived from the original (PDF) on 2016-03-07.
- S2CID 7676548.
- PMID 10424513.
- ^ "randomhouse author search". Archived from the original on 2011-03-07. Retrieved 2009-04-20.
- ^ "Ortho-McNeill, Johnson & Johnson, Daichi v. Mylan" (PDF). Archived from the original (PDF) on 2008-09-16. Retrieved 2009-10-25.
- ^ Drugs.com. "Complete Ofloxacin information from Drugs.com". Archived from the original on 2016-03-03.
- PMID 9293187.
- ISBN 978-0-470-01552-0. Archivedfrom the original on 8 September 2017.
- ^ PMID 18611493.
- ^ a b Atarashi S. "Research and Development of Quinolones in Daiichi Sankyo Co., Ltd" (PDF). Daiichi. Archived from the original (PDF) on 12 October 2016. Retrieved 25 August 2016.
- ^ "LEVAQUIN Ortho-McNeil Pharmaceutical, Inc. v. Lupin Pharmaceutical, Inc. C.A. No. 06-04999-GEB-TJB May 1, 2009 Memorandum Opinion" (PDF). memorANDA. Fish & RichaRdson P.C. April 2009. p. VIII. Archived from the original (PDF) on 2016-08-27. Cites US 4382892, Hayakawa I, Hiramitsu T, Tanaka Y, "Benzoxazine derivatives", issued 10 May 1983, assigned to Daiichi Pharmaceutical Co. Ltd.
- ^ a b "Johnson & Johnson Going Into 1991 With At Least Four New Product Launches: Floxin, Vascor, Procrit And Duragesic; J&J Leading Off With Procrit, Vascor". The Pink Sheet. 7 January 1991. Archived from the original on 26 August 2016.
- PMID 8363378.
- ^ "Floxin Tablets (ofloxacin tablets)". CenterWatch. Floxin Tablets New FDA Drug Approval. Archived from the original on April 13, 2016. Retrieved August 25, 2016.
- ^ "Floxin otic New FDA Drug Approval". Archived from the original on 2016-08-27.
- ^ "Teva Announces Approval of Ofloxacin Tablets, 200 mg, 300 mg, and 400 mg". Business Wire. September 2, 2003.
- ^ Johnson & Johnson (2003). "Building on a foundation of health" (PDF). Shareholder. Archived from the original (PDF) on 2011-10-01. Retrieved 2009-05-15.
- ^ "Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications". Federal Register 74(95):23407-23412. May 19, 2009. Archived from the original on September 19, 2016.
see also FDA docket number FDA-2009-N-0211
- ^ "Ofloxacin". go.drugbank.com. Retrieved 2022-11-16.
- ^ Jacobs M (2005). "Worldwide overview of antimicrobial Resistance.". International Symposium on Antimicrobial Agents and Resistance. Drugs. Republic of Korea. pp. 542–546.
{{cite book}}
: CS1 maint: location missing publisher (link) - PMID 15745724.