Levofloxacin is a synthetic broad-spectrum antibacterial agent for oral and intravenous administration. Chemically, levofloxacin, a chiral fluorinated carboxyquinolone, is the pure (-)-(S)-enantiomer of the racemic drug substance ofloxacin. The chemical name is (-)-(S)-9fluoro-2, 3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido [1, 2, 3-de]-1, 4benzoxazine-6-carboxylic acid hemihydrate.
The empirical formula is C18H20FN3O4 • ½ H2O and the molecular weight is 370.38. Levofloxacin is a light yellowish-white to yellow-white crystal or crystalline powder. The molecule exists as a zwitterion at the pH conditions in the small intestine. The data demonstrate that from pH 0.6 to 5.8, the solubility of levofloxacin is essentially constant (approximately 100 mg/mL).
Levofloxacin is considered soluble to freely soluble in this pH range, as defined by USP nomenclature. Above pH 5.8, the solubility increases rapidly to its maximum at pH 6.7 (272 mg/mL) and is considered freely soluble in this range. Above pH 6.7, the solubility decreases and reaches a minimum value (about 50 mg/mL) at a pH of approximately 6.9.
Gram positive bacteria: methicillin-susceptible Staphylococcus aureus (MSSA), methicillinresistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Listeria monocytogenes.
Gram negativebacteria: Enterobacteriaceae, H. influenzae, other Haemophilus spp., N.gonorrhoeae, N. meningitides, M. catarrhalis, P. aeruginosa, Stenotrophomonas maltophilia, S.maltophilia.
Atypicals: Legionella pneumophilia
Treatment of community-acquired pneumonia, including multidrug resistant strains of S. pneumoniae (MDRSP); nosocomial pneumonia; chronic bronchitis (acute bacterial exacerbation); acute bacterial rhinosinusitis (ABRS); prostatitis (chronic bacterial), urinary tract infection (uncomplicated or complicated); acute pyelonephritis; skin or skin structure infections (uncomplicated or complicated); reduce incidence or disease progression of inhalational anthrax (post exposure); prophylaxis and treatment of plague (pneumonic and septicemia) due to Y. pestis.
Mechanism of Action:
Inhibition of topoisomerase (DNA gyrase) enzymes, which inhibits relaxation of supercoiled DNA and promotes breakage of double stranded DNA.
Dosage: Oral: 250mg, 500mg, 750mg tablet
Intravenous: 25mg/ml solution
Opthalmic: 0.5% solution
Inhalational anthrax, postexposure prophylaxis: 500 mg PO/IV every 24 hr for 60 days
Chronic bronchitis: 500 mg PO/IV every 24 hr for 7 days
Chronic prostatitis: 500 mg PO/IV every 24 hr for 28 days
Community-acquired pneumonia: 500 mg PO/IV every 24 hr for 7-14 days or 750 mg PO/IV or every 24 hr for 5 days
Nosocomial pneumonia: 750 mg PO/IV every 24 hr for 7-14 days
Pyelonephritis: 250 mg PO/IV every 24 hr for 10 days
Sinusitis: 500 mg PO/IV every 24 hr for 10-14 days
Skin/skin structure infection: uncomplicated, 500 mg PO/IV every 24 hr for 7-10 days; complicated, 750 mg PO/IV every 24 hr for 7-14 days
Urinary tract infection: uncomplicated, 250 mg PO/IV every 24 hr for 3 days; complicated, 250 mg IV or ORALLY every 24 hr for 10 days
Conjunctivitis, bacterial: (0.5% ophthalmic solution) day 1-2, 1-2 drops every 2 hr while awake (MAX 8 times/day); day 3-7, 1-2 drops every 4 hr while awake (MAX 4 times/day)
Corneal ulcer: (1.5% ophthalmic solution) day 1-3, 1-2 drops every 30 min to 2 hr while awake and 4 hr and 6 hr after retiring; day 4 through treatment end, 1-2 drops every 1 to 4 hr while awake
Conjunctivitis, bacterial: (0.5% ophthalmic solution) ages 1 year and older; day 1-2, 1-2 drops every 2 hr while awake (MAX 8 times/day); day 3-7, 1-2 drops every 4 hr while awake (MAX 4 times/day)
Corneal ulcer: (1.5% ophthalmic solution) ages 6 year and older; day 1-3, 1-2 drops every 30 min to 2 hr while awake and 4 hr and 6 hr after retiring; day 4 through treatment end, 1-2 drops every 1 to 4 hr while awake
- Prolongation of QT interval; avoid concurrent use with other drugs that prolong QT interval and in patients with risk factors for torsades de pointes (hypokalemia, significant bradycardia, cardiomyopathy)
- Patients with glucose 6-phosphate dehydrogenase deficiency
- Diabetes mellitus; disturbances of blood glucose have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or with insulin
Divalent cations: aluminum, magnesium zinc, iron, calcium, antacids, sucralfate – reduced bioavailability of quinolones (can cause therapeutic failure)
Theophylline, caffeine, xanthines: clearance of these is inhibited with fluoroquinolones
Pregnancy: Category C: Risk unknown. Human studies inadequate.