patients experienced nausea, 6% headache, 5% diarrhea, 4% insomnia, along with other adverse reactions experienced at lower rates. administration of levofloxacin or other broad spectrum antibiotics is associated with clostridium difficile associated diarrhea which may range in severity from mild diarrhea to fatal colitis. fluoroquinoline administration may be associated with the acquisition and outgrowth of a particularly virulent clostridium strain. more research is needed to determine the best dose and length of treatment. overdose overdosing experiments in animals showed loss of body control and drooping, difficulty breathing, tremors, and convulsions. doses in excess of 1500 mg/kg orally and 250 mg/kg iv produced significant mortality in rodents. in the event of an acute overdosage, authorities recommend unspecific standard procedures such as emptying the stomach, observing the patient and maintaining appropriate hydration. levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis. pharmacology mechanism of action levofloxacin is a broad-spectrum antibiotic that is active against both gram-positive and gram-negative bacteria. like all quinolones, it functions by inhibiting the dna gyrase and topoisomerase iv, two bacterial type iia topoisomerases. topoisomerase iv is necessary to separate dna that has been replicated (doubled) prior to bacterial cell division. with the dna not being separated, the process is stopped, and the bacterium cannot divide. dna gyrase, on the other hand, is responsible for supercoiling the dna, so that it will fit in the newly formed cells. both mechanisms amount to killing the bacterium. levofloxacin acts as a bactericide. as of 2011, the mechanism of action for the drug's musculoskeletal complications were not clear. pharmacokinetics levofloxacin is rapidly and essentially completely absorbed after oral administration, with a plasma concentration profile over time that is essentially identical to that obtained from intravenous administration of the same amount over 60 minutes. as such, the intravenous and oral formulations of levofloxacin are considered interchangeable. levofloxacin's ability to bind to proteins in the body ranges from 24 to 38%. the drug undergoes widespread distribution into body tissues. peak levels in skin are achieved 3 hours after administration and exceed those in plasma by a factor of 2. similarly, lung tissue concentrations range from two-fold to five-fold higher than plasma concentrations in the 24 hours after a single dose. the mean terminal plasma elimination half-life of levofloxacin ranges from approximately 6 to 8 hours following single or multiple doses of levofloxacin given orally or intravenously. elimination occurs mainly via excretion of unmetabolized drug in the urine. following oral administration, 87% of an administered dose was recovered in the urine as unchanged drug within 2 days. less than 5% was recovered in the urine as the desmethyl and n-oxide metabolites, the only metabolites identified in humans. chemistry like all fluoroqinolones, levofloxacin is a fluorinated quinolone carboxylic acid. it is a chiral molecule and the pure (−)-(s)-enantiomer of the racemic drug ofloxacin. this enantiomer binds more effectively to the dna gyrase enzyme and to topoisomerase iv than its (+)-(r)-counterpart. levofloxacin is referred to as a chiral switch: these are chiral drugs that have already been patent claimed, approved and marketed as racemates (or as mixtures of diastereomers but have since been redeveloped as pure enantiomers. distinct functional groups on this molecules include a hydroxyl group, carbonyl group, and an aromatic ring. the substance is used as the hemihydrate, which has the empirical formula c18h20fn3o4 · 1⁄2 h2o and a molecular mass of 370.38 g/mol. levofloxacin is a light-yellowish-white to yellow-white crystal or crystalline powder. a major issue in the synthesis of levofloxacin is identifying correct entries into the benzoxazine core in order to produce the correct chiral form. history levofloxacin is a third-generation fluoroquinolone, being one of the isomers of ofloxacin, which was a broader-spectrum conformationally locked analog of norfloxacin; both ofloxacin and levofloxaxin were synthesized and developed by scientists at daiichi seiyaku. the daiichi scientists knew that ofloxacin was racemic, but tried unsuccessfully to separate the two isomers; in 1985 they succeeded in separately synthesizing the pure levo form and showed that it was less toxic and more potent than the other form. it was first approved for marketing in japan in 1993, for oral administration, and daiichi marketed it there under the brand name cravit. daiichi, working with johnson & johnson as it had with ofloxacin, obtained fda approval in 1996 under the brand name levaquin to treat bacterial sinusitus, bacterial exacerbations of bronchitis, community-acquired pneumonia, uncomplicated skin infections, complicated urinary tract infections, and acute pyelonephritis. levofloxacin is marketed by sanofi-aventis under a license agreement signed with daiichi in 1993, under the brand name "tavanic". levofloxacin had reached blockbuster status by this time; combined worldwide sales of levofloxacin and ofloxacin for j&j alone were us$1.6 billion in 2009. the term of the levofloxacin united states patent was extended by the u.s. patent and trademark office 810 days under the provisions of the hatch waxman amendment so that the patent would expire in 2010 instead of 2008. this extension was challenged by generic drug manufacturer lupin pharmaceuticals, which did not challenge the validity of the patent, but only the validity of the patent extension, arguing that the patent did not cover a "product" and so hatch-waxman was not available for extensions. the federal patent court ruled in favor of j&j and daiichi, and generic versions of levofloxacin did not enter the u.s. market until 2009. in russia, the drug is produced by binnopharm group society and culture availability levofloxacin and nacl injection, specification is 100ml / 750mg levofloxacin is available in tablet form, injection, and oral solution. usage the fda estimated that in 2011, over 23 million outpatient prescriptions for fluoroquinolones, of which levofloxacin made up 28%, were filled in the united states. litigation as of 2012, johnson and johnson was facing around 3400 state and federal lawsuits filed by people who claimed tendon damage from levofloxacin; about 1900 pending in a class action at the united states district court in minnesota and about 1500 pending at a district court in new jersey. in october 2012, j&j settled 845 cases in the minnesota action, after johnson and johnson prevailed in three of the first four cases to go to trial. by may 2014, all but 363 cases had been settled or adjudicated.