|Systematic (IUPAC) name|
|Trade names||Floxin, Ocuflox|
|Routes||Oral, IV, topical (eye drops and ear drops)|
|Bioavailability||85% - 95%|
|ATC code||J01 ,S01, S02|
|Mol. mass||361.368 g/mol|
|(what is this?)|
Ofloxacin is a synthetic antibiotic of the fluoroquinolone drug class considered to be a second-generation fluoroquinolone. The original brand, Floxin, has been discontinued by the manufacturer in the United States on 18 June 2009, though generic equivalents continue to be available.
Ofloxacin was first patented in 1982 (European Patent Daiichi) and received approval from the U.S. Food and Drug Administration (FDA) on December 28, 1990. Ofloxacin is sold under a wide variety of brand names as well as generic drug equivalents, for oral and intravenous administration. Ofloxacin is also available for topical use, as eye drops and ear drops (marketed as Ocuflox and Floxin Otic respectively in the United States and marketed as Optiflox, eylox respectively in Jordan and Saudi Arabia).
Ofloxacin has been associated with adverse drug reactions, such as tendon damage (including spontaneous tendon ruptures) and peripheral neuropathy (which may be irreversible); tendon damange may manifest long after therapy had been completed, and, in severe cases, may result in lifelong disabilities.
Ofloxacin was developed as a broader-spectrum analog of norfloxacin, the first fluoroquinolone antibiotic, Ofloxacin was first patented in 1982 (European Patent Daiichi) and received U.S. Food and Drug Administration (FDA) approval December 28, 1990.
In the United States name branded ofloxacin is rarely used anymore, having been discontinued by the manufacturer, Ortho-McNeil-Janssen, a subsidiary of Johnson & Johnson. Johnson and Johnson's annual sales of Floxin in 2003 was approximately $30 million, whereas their combined sales of Levaquin/Floxin exceeded $1.15 billion in the same year. However generic use continues. The FDA website lists Floxin (Ortho McNeil Jannsen) as being discontinued, with just a few generic equivalents still in use. The otic solution continues to be listed as being available both as an original drug as well as a generic equivalent.
In the in the U.S. ofloxacin is approved for the treatment of bacterial infections such as:
- Acute bacterial exacerbations of chronic bronchitis
- Community-acquired pneumonia
- Uncomplicated skin and skin structure infections
- Uncomplicated cystitis
- Complicated urinary tract infections
- Acute, uncomplicated urethral and cervical gonorrhea.
Ofloxacin for systemic use is available as tablet (multiple strengths), oral solution (250 mg/mL), and injectable solution (multiple strengths). It is also used as eye drops and ear drops. It is also available in combination with ornidazole.
Mode of action
Ofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, which is an enzyme necessary to separate (mostly in prokaryotes, in bacteria in particular) replicated DNA, thereby inhibiting bacterial cell division.
Due to growing prevalence of antibiotic resistance to the fluoroquinolones in southeast Asia, the use of ofloxacin in patients who have been to southeast Asia is increasingly being contraindicated.
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.
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 (4 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 (5 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. 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.
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 (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 post-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, approximately 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 the 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 5 cases of tendon rupture) and central nervous system events (19, including 5 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.
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.
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 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 is 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, as well as up to a year after fluoroquinolone therapy has been completed.
FQs 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 (ciprofloxacin and levofloxacin) only minimally prolong the QT interval.
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 that is similar to or less  than that associated with broad spectrum cephalosporins. Fluoroquinoline administration may be associated with the acquisition and outgrowth of a particularly virulent Clostridium strain.
The U.S. 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 renal 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, theophyline, 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 anti-diabetes drugs.
The concomitant administration of a non-steroidal anti-inflammatory drug with a quinolone, including ofloxacin, may increase the risk of CNS stimulation and convulsive seizures.
The fluoroquinolones have been shown to increase the anticoagulant effect of Acenocoumarol, Anisindione, and Dicumarol. Additionally there is an increase the risk of cardiotoxicity and arrhythmias when co administered with drugs such as Dihydroquinidine barbiturate, Quinidine, and Quinidine barbiturate.
There is limited information on overdose with ofloxacin. Current advise 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. Overdose may result in central nervous system toxicity, cardiovascular toxicity, tendon/articular toxicity, and hepatic toxicity as well as renal failure and seizure. Seizures have however, been reported to occur at therapeutic dosage as well as severe psychiatric reactions.
The bioavailability of ofloxacin in the tablet form is approximately 98% following oral administration reaching maximum serum concentrations within one to two hours. Between 65% and 80% of an administered oral dose of ofloxacin is excreted unchanged via the kidneys within 48 hours of dosing. Therefore elimination is mainly by renal excretion. However, four to eight percent of an ofloxacin dose is excreted in the feces. This would indicate a small degree of biliary excretion as well. Plasma elimination half-life is approximately 4 to 5 hours in patients and approximately 6.4 to 7.4 hours in elderly patients.
"After multiple-dose administration 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. 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."
There are a number of the endogenous compounds that have been reported to be affected by ofloxacin as inhibitors, alteraters and depletors. See the latest package insert for Ofloxacin for additional details.
Ofloxacin should be administered as described within the Dosage Guidelines table found within the most current package insert. The status of the patient’s renal function and hepatic function must also be taken into consideration to avoid an accumulation that may lead to a fatal drug overdose. Ofloxacin is eliminated primarily by renal excretion. However, the drug is also metabolized and partially cleared through the liver. Modification of the dosage is required using the table found within the package insert for those with impaired liver or kidney function (Particularly for patients with severe renal dysfunction). However, since the drug is known to be substantially excreted by the kidneys, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. The duration of treatment depends upon the severity of infection and the usual duration is 7 to 14 days.
According to the product packing insert, ofloxacin is effective against the following microorganisms.
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"
Antibiotic abuse and bacterial resistance
Resistance to ofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous pathogens, including Staphylococcus aureus, enterococci, and Streptococcus pyogenes now exhibit resistance worldwide.
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 FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study that was supported in part by the Agency for Healthcare Research and Quality. 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.
- Nelson, JM.; Chiller, TM.; Powers, JH.; Angulo, FJ. (Apr 2007). "Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: a public health success story". Clin Infect Dis 44 (7): 977–80. doi:10.1086/512369. PMID 17342653.
- Kawahara, S. (December 1998). "[Chemotherapeutic agents under study]". Nippon Rinsho 56 (12): 3096–9. PMID 9883617.
- Clodagh Sheehy (August 2, 2008). "Warning over two types of antibiotic". Republic of Ireland. Retrieved July 17, 2009.
- Mark B. Abelson, MD; Stephen J. Hallas (April 15, 2003). "The New Antibiotics: The Path of Least Resistance". Review of Ophthalmology. Retrieved October 3, 2009.
- Douglas C. Throckmorton (May 19, 2009). "Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications". Trading Markets.
see also FDA docket number FDA-2009-N-0211
- Business Wire (September 2, 2003). "Teva Announces Approval of Ofloxacin Tablets, 200 mg, 300 mg, and 400 mg". Business Wire.
- Johnson & Johnson (2003). "Building on a foundation of health" (PDF). Shareholder.
- Ortho-McNeil-Janssen Pharmaceuticals, Inc (2008). "FLOXIN Tablets (Ofloxacin Tablets)" (PDF). USA: FDA.
- Susan Blank; Julia Schillinger (May 14, 2004). "DOHMH ALERT #8:Fluoroquinolone-resistant gonorrhea, NYC". USA: New York County Medical Society. Retrieved July 22, 2009.
- Knapp JS, Fox KK, Trees DL, Whittington WL; Fox; Trees; Whittington (1997). "Fluoroquinolone resistance in Neisseria gonorrhoeae". Emerging Infect. Dis. 3 (1): 33–9. doi:10.3201/eid0301.970104. PMC 2627594. PMID 9126442.
- Dan M (April 2004). "The use of fluoroquinolones in gonorrhoea: the increasing problem of resistance". Expert Opin Pharmacother 5 (4): 829–54. doi:10.1517/146565184.108.40.2069. PMID 15102567. Retrieved 2014-09-28.
- Drlica K, Zhao X; Zhao (1 September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiol Mol Biol Rev. 61 (3): 377–92. PMC 232616. PMID 9293187.
- Centers for Disease Control and Prevention (CDC) (October 1995). "Fluoroquinolone resistance in Neisseria gonorrhoeae—Colorado and Washington, 1995". MMWR Morb Mortal Wkly Rep. 44 (41): 761–4. PMID 7565558.
- Coban S, Ceydilek B, Ekiz F, Erden E, Soykan I; Ceydilek; Ekiz; Erden; Soykan (October 2005). "Levofloxacin-induced acute fulminant hepatic failure in a patient with chronic hepatitis B infection". Ann Pharmacother 39 (10): 1737–40. doi:10.1345/aph.1G111. PMID 16105873.
- Pharmacotherapy: Official Journal of the American College of Clinical Pharmacy Print ISSN: 0277-0008 Volume: 25 | Issue: 1 Cover date: January 2005 Page(s): 116-118
- Nardiello, S, Pizzella, T, Ariviello, R (March 2002). "Risks of antibacterial agents in pregnancy". Le infezioni in medicina : rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive 10 (1): 8–15. PMID 12700435.
- Noel GJ, Bradley JS, Kauffman RE; Bradley; Kauffman; Duffy; Gerbino; Arguedas; Bagchi; Balis; Blumer (October 2007). "Comparative safety profile of levofloxacin in 2523 children with a focus on four specific musculoskeletal disorders". Pediatr. Infect. Dis. J. 26 (10): 879–91. doi:10.1097/INF.0b013e3180cbd382. PMID 17901792.
- Owens RC, Ambrose PG; Ambrose (July 2005). "Antimicrobial safety: focus on fluoroquinolones". Clin. Infect. Dis. 41 Suppl 2: S144–57. doi:10.1086/428055. PMID 15942881.
- De Sarro A, De Sarro G; De Sarro (March 2001). "Adverse reactions to fluoroquinolones. an overview on mechanistic aspects". Curr. Med. Chem. 8 (4): 371–84. doi:10.2174/0929867013373435. PMID 11172695.
- Skalsky K, Yahav D, Lador A, Eliakim-Raz N, Leibovici L, Paul M; Yahav; Lador; Eliakim-Raz; Leibovici; Paul (April 2013). "Macrolides vs. quinolones for community-acquired pneumonia: meta-analysis of randomized controlled trials". Clin. Microbiol. Infect. 19 (4): 370–8. doi:10.1111/j.1469-0691.2012.03838.x. PMID 22489673.
- Falagas ME, Matthaiou DK, Vardakas KZ; Matthaiou; Vardakas (December 2006). "Fluoroquinolones vs beta-lactams for empirical treatment of immunocompetent patients with skin and soft tissue infections: a meta-analysis of randomized controlled trials". Mayo Clin. Proc. 81 (12): 1553–66. doi:10.4065/81.12.1553. PMID 17165634.
- Van Bambeke F, Tulkens PM; Tulkens (2009). "Safety profile of the respiratory fluoroquinolone moxifloxacin: comparison with other fluoroquinolones and other antibacterial classes". Drug Saf 32 (5): 359–78. doi:10.2165/00002018-200932050-00001. PMID 19419232.
- Shehab N, Patel PR, Srinivasan A, Budnitz DS; Patel; Srinivasan; Budnitz (September 2008). "Emergency department visits for antibiotic-associated adverse events". Clin. Infect. Dis. 47 (6): 735–43. doi:10.1086/591126. PMID 18694344.
- Kim GK (April 2010). "The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture: What Does The Clinician Need To Know?". J Clin Aesthet Dermatol 3 (4): 49–54. PMC 2921747. PMID 20725547.
- Sode J, Obel N, Hallas J, Lassen A; Obel; Hallas; Lassen (May 2007). "Use of fluroquinolone and risk of Achilles tendon rupture: a population-based cohort study". Eur. J. Clin. Pharmacol. 63 (5): 499–503. doi:10.1007/s00228-007-0265-9. PMID 17334751.
- Owens RC, Ambrose PG; Ambrose (July 2005). "Antimicrobial safety: focus on fluoroquinolones". Clin. Infect. Dis. 41 Suppl 2: S144–57. doi:10.1086/428055. PMID 15942881.
- Khaliq Y, Zhanel GG; Zhanel (October 2005). "Musculoskeletal injury associated with fluoroquinolone antibiotics". Clin Plast Surg 32 (4): 495–502, vi. doi:10.1016/j.cps.2005.05.004. PMID 16139623.
- Saint F, Gueguen G, Biserte J, Fontaine C, Mazeman E; Gueguen; Biserte; Fontaine; Mazeman (September 2000). "[Rupture of the patellar ligament one month after treatment with fluoroquinolone]". Rev Chir Orthop Reparatrice Appar Mot (in French) 86 (5): 495–7. PMID 10970974.
- Heidelbaugh JJ, Holmstrom H; Holmstrom (April 2013). "The perils of prescribing fluoroquinolones". J Fam Pract 62 (4): 191–7. PMID 23570031.
- Rubinstein E, Camm J; Camm (April 2002). "Cardiotoxicity of fluoroquinolones". J. Antimicrob. Chemother. 49 (4): 593–6. doi:10.1093/jac/49.4.593. PMID 11909831.
- Deshpande A, Pasupuleti V, Thota P et al. (September 2013). "Community-associated Clostridium difficile infection and antibiotics: a meta-analysis". J. Antimicrob. Chemother. 68 (9): 1951–61. doi:10.1093/jac/dkt129. PMID 23620467.
- Slimings C, Riley TV; Riley (December 2013). "Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis". J. Antimicrob. Chemother. 69 (4): 881–91. doi:10.1093/jac/dkt477. PMID 24324224.
- "Data Mining Analysis of Multiple Antibiotics in AERS".
- Vardakas KZ, Konstantelias AA, Loizidis G, Rafailidis PI, Falagas ME; Konstantelias; Loizidis; Rafailidis; Falagas (November 2012). "Risk factors for development of Clostridium difficile infection due to BI/NAP1/027 strain: a meta-analysis". Int. J. Infect. Dis. 16 (11): e768–73. doi:10.1016/j.ijid.2012.07.010. 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".
- Galatti L, Giustini SE, Sessa A et al. (March 2005). "Neuropsychiatric reactions to drugs: an analysis of spontaneous reports from general practitioners in Italy". Pharmacol. Res. 51 (3): 211–6. doi:10.1016/j.phrs.2004.08.003. PMID 15661570.
- Babar, S. (October 2013). "SIADH Associated With Ciprofloxacin.". The Annals of Pharmacotherapy (Sage Publishing) 47 (10): 1359–1363. doi:10.1177/1060028013502457. ISSN 1060-0280. PMID 24259701. Retrieved November 139,2013. Check date values in:
- Rouveix, B. (Nov–Dec 2006). "[Clinically significant toxicity and tolerance of the main antibiotics used in lower respiratory tract infections]". Med Mal Infect 36 (11–12): 697–705. doi:10.1016/j.medmal.2006.05.012. PMID 16876974.
- Mehlhorn AJ, Brown DA; Brown (November 2007). "Safety concerns with fluoroquinolones". Annals of Pharmacotherapy 41 (11): 1859–66. doi:10.1345/aph.1K347. PMID 17911203.
- Jones SF, Smith RH; Smith (March 1997). "Quinolones may induce hepatitis". BMJ 314 (7084): 869. doi:10.1136/bmj.314.7084.869. PMC 2126221. PMID 9093098.
- Nelson, Lewis H.; Flomenbaum, Neal; Goldfrank, Lewis R.; Hoffman, Robert Louis; Howland, Mary Deems; Neal A. Lewin (2006). Goldfrank's toxicologic emergencies. New York: McGraw-Hill, Medical Pub. Division. ISBN 0-07-143763-0.
- Iannini PB (June 2007). "The safety profile of moxifloxacin and other fluoroquinolones in special patient populations". Curr Med Res Opin 23 (6): 1403–13. doi:10.1185/030079907X188099. PMID 17559736.
- Farinas, Evelyn R; PUBLIC HEALTH SERVICE FOOD AND DRUG ADMINISTRATION CENTER FOR DRUG EVALUATION AND RESEARCH (1 March 2005). "Consult: One-Year Post Pediatric Exclusivity Postmarketing Adverse Events Review" (PDF). USA: FDA. Retrieved 31 August 2009.
- "Showing drug card for Ofloxacin (DB01165)". Canada: DrugBank. February 19, 2009.
- van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HM, Rowlands S, Stricker BH, PD; Sturkenboom, MC; Herings, RM; Leufkens, HM; Rowlands, S; Stricker, BH (August 2003). "Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids". Arch. Intern. Med. 163 (15): 1801–7. doi:10.1001/archinte.163.15.1801. ISSN 0003-9926. PMID 12912715.
- Hall, CE; Keegan, H; Rogstad, KE (September 2003). "Psychiatric side effects of ofloxacin used in the treatment of pelvic inflammatory disease". Int J STD AIDS 14 (9): 636–7. doi:10.1258/095646203322301121. PMID 14511503.
- Amsden, GW; Graci, DM; Cabelus, LJ; Hejmanowski, LG (July 1999). "A randomized, crossover design study of the pharmacology of extended-spectrum fluoroquinolones for pneumococcal infections" (PDF). Chest 116 (1): 115–9. doi:10.1378/chest.116.1.115. PMID 10424513.
- Drugs.com. "Complete Ofloxacin information from Drugs.com".
- Sato K, Matsuura Y, Inoue M, Une T, Osada Y, Ogawa H, Mitsuhashi S; Matsuura; Inoue; Une; Osada; Ogawa; Mitsuhashi (October 1982). "In vitro and in vivo activity of DL-8280, a new oxazine derivative". Antimicrob. Agents Chemother. 22 (4): 548–53. doi:10.1128/aac.22.4.548. PMC 183791. PMID 6960805. Retrieved 2014-09-28.
- M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005.
- Linder JA, Huang ES, Steinman MA, Gonzales R, Stafford RS; Huang; Steinman; Gonzales; Stafford (March 2005). "Fluoroquinolone prescribing in the United States: 1995 to 2002". Am. J. Med. 118 (3): 259–68. doi:10.1016/j.amjmed.2004.09.015. PMID 15745724.
- K08 HS14563 and HS11313
- Ofloxacin: an overview - A site with its chemical properties and alternate brand names.
- U.S. National Library of Medicine: Drug Information Portal - Ofloxacin
- Package insert links