Levofloxacin

(BAN, USAN, rINN)
Levofloxacin Chemical formula
Synonyms: DR-3355; HR-355; Levofloksasiini; Levofloksasin; Lévofloxacine; Levofloxacino; Levofloxacinum; S-(−)-Ofloxacin; RWJ-25213. (− )-(S)-9-Fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3de]-1,4-benzoxazine-6-carboxylic acid.
Cyrillic synonym: Левофлоксацин.

💊 Chemical information

Chemical formula: C18H20FN3O4 = 361.4.
CAS — 100986-85-4 (levofloxacin); 138199-71-0 (levofloxacin hemihydrate).
ATC — J01MA12; S01AX19.
ATC Vet — QJ01MA12; QS01AX19.

💊 Adverse Effects and Precautions

As for Ciprofloxacin. Symptomatic hyperglycaemia and/or hypoglycaemia have been reported, usually in diabetics who are also taking hypoglycaemics or insulin. Such patients should have their blood-glucose concentrations closely monitored and if signs or symptoms of glucose disturbances develop, levofloxacin should be stopped.

Effects on glucose metabolism.

See also under Gatifloxacin.

💊 Interactions

As for Ciprofloxacin. Use of levofloxacin with drugs that alter blood-glucose concentrations increases the risk of blood-glucose disturbances. Levofloxacin does not appear to interact significantly with theophylline or ciclosporin.

💊 Antimicrobial Action

As for Ciprofloxacin. Levofloxacin is generally considered to be about twice as active as ofloxacin, the racemic substance. Levofloxacin has a broad spectrum of activity which includes Gram-positive bacteria.
1. Brown DFJ, et al., eds. Levofloxacin: an extended spectrum 4quinolone agent. J Antimicrob Chemother 1999; 43 (suppl C): 1–90.

💊 Pharmacokinetics

Levofloxacin is rapidly and almost completely absorbed after oral doses with peak plasma concentrations occurring within 1 to 2 hours. It is widely distributed into body tissues including the bronchial mucosa and lungs, but penetration into CSF is relatively poor. Levofloxacin is about 30 to 40% bound to plasma proteins. Only small amounts are metabolised, to inactive metabolites. The elimination half-life of levofloxacin is 6 to 8 hours, although this may be prolonged in patients with renal impairment. Levofloxacin is excreted largely unchanged, primarily in the urine with less than 5% as metabolites. It is not removed by haemodialysis or peritoneal dialysis.
1. Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet 1997; 32: 101–19
2. Piscitelli SC, et al. Pharmacokinetics and safety of high-dose and extended-interval regimens of levofloxacin in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 1999; 43: 2323–7.

💊 Uses and Administration

Levofloxacin is the S-(−)-isomer of the fluoroquinolo
ne antibacterial ofloxacin. It is given orally, or by intravenous infusion as a 5 mg/mL solution over 30 to 90 minutes, to treat susceptible infections including tuberculosis. Levofloxacin is given as the hemihydrate but doses are expressed in terms of the base; levofloxacin hemihydrate 256 mg is equivalent to about 250 mg of levofloxacin. Usual doses range from 250 to 500 mg once or twice daily for 7 to 14 days depending on the severity and nature of the infection. A dose of 250 mg once daily for 3 days may be given for uncomplicated urinary-tract infections. A 28-day course of treatment with a dose of 500 mg once daily should be given for chronic bacterial prostatitis. In the USA, doses of 750 mg once daily for 7 to 14 days may be used for complicated skin infections and for hospital-acquired pneumonia; a shorter course of 750 mg once daily for 5 days may be given for community-acquired pneumonia, acute bacterial sinusitis, complicated urinary-tract infections, and acute pyelonephritis. A 60-day course of treatment with a dose of 500 mg once daily is also licensed in the USA for treatment and postexposure prophylaxis of inhalation anthrax. Doses should be reduced in patients with renal impairment (see below). Levofloxacin is also used topically as the hemihydrate in eye drops. A solution containing the equivalent of 0.5% of levofloxacin is used for the treatment of bacterial conjunctivitis and 1.5% for corneal ulcers caused by susceptible strains of bacteria.
1. Davis R, Bryson HM. Levofloxacin: a review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs 1994; 4: 677–700
2. Martin SJ, et al. Levofloxacin and sparfloxacin: new quinolone antibiotics. Ann Pharmacother 1998; 32: 320–36
3. Martin SJ, et al. A risk-benefit assessment of levofloxacin in respiratory, skin and skin structure, and urinary tract infections. Drugs 2001; 24: 199–222
4. Croom KF, Goa KL. Levofloxacin: a review of its use in the treatment of bacterial infections in the United States. Drugs 2003; 63: 2769–2802
5. Anderson VR, Perry CM. Levofloxacin: a review of its use as a high-dose, short-course treatment for bacterial infection. Drugs 2008; 68: 535–65.

Administration in children.

Since fluoroquinolones can cause degenerative changes in weight-bearing joints of young animals they should only be used in children and adolescents where their use may be justified if the benefits outweigh the risks. Although levofloxacin is not licensed for use in this age group in either the UK or USA, a pharmacokinetic study1 has suggested that the following doses would be needed:
children 5 years of age and older, 10 mg/kg daily
infants and children from 6 months to less than 5 years of age, 10 mg/kg every 12 hours
1. Chien S, et al. Levofloxacin pharmacokinetics in children. J Clin Pharmacol 2005; 45: 153–60.

Administration in renal impairment.

Although initial doses (see above) remain unchanged in patients with renal impairment, subsequent doses of levofloxacin should be adjusted according to creatinine clearance (CC). In the UK, the following doses are recommended:
CC 20 to 50 mL/minute: subsequent doses are halved
CC 10 to 19 mL/minute: subsequent doses are reduced to onequarter of the usual dose; a regimen of 250 mg daily should be reduced to 125 mg every 48 hours
CC less than 10 mL/minute (including haemodialysis and continuous peritoneal dialysis patients): usual doses of 250 mg or 500 mg daily are reduced to 125 mg every 48 or 24 hours respectively; a regimen of 500 mg twice daily is reduced to 125 mg every 24 hours In the USA, the following dose modifications are recommended: After an initial dose of 750 mg daily,
CC 20 to 49 mL/minute: subsequent doses are 750 mg every 48 hours
CC up to 19 mL/minute (including haemodialysis and continuous peritoneal dialysis patients): subsequent doses are 500 mg every 48 hours After an initial dose of 500 mg daily,
CC 20 to 49 mL/minute: subsequent doses are 250 mg every 24 hours
CC up to 19 mL/minute (including haemodialysis and continuous peritoneal dialysis patients): subsequent doses are 250 mg every 48 hours After an initial dose of 250 mg daily,
CC 10 to 19 mL/minute: subsequent doses are 250 mg every 48 hours A pharmacokinetic study in 10 critically ill patients undergoing continuous renal replacement therapy with either venovenous haemofiltration or haemodiafiltration suggested that a dose of either levofloxacin 250 mg every 24 hours or 500 mg every 48 hours would be suitable in such situations.1
1. Malone RS, et al. Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in critically ill patients. Antimicrob Agents Chemother 2001; 45: 2949–54.

Peptic ulcer disease.

For mention of the potential use of levofloxacin in eradication regimens for Helicobacter pylori.
1. Gisbert JP, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Aliment Pharmacol Ther 2006; 23: 35–44
2. Gisbert JP, et al. First-line triple therapy with levofloxacin for Helicobacter pylori eradication. Aliment Pharmacol Ther 2007; 26: 495–500
3. Rispo A, et al. Levofloxacin in first-line treatment of Helicobacter pylori infection. Helicobacter 2007; 12: 364–5
4. Perna F, et al. Levofloxacin-based triple therapy for Helicobacter pylori re-treatment: role of bacterial resistance. Dig Liver Dis 2007; 39: 1001–5
5. Zullo A, et al. Helicobacter pylori eradication with either quadruple regimen with lactoferrin or levofloxacin-based triple therapy: a multicentre study. Dig Liver Dis 2007; 39: 806–10
6. Yee YK, et al. Clinical trial: levofloxacin-based quadruple therapy was inferior to traditional quadruple therapy in the treatment of resistant Helicobacter pylori infection. Aliment Pharmacol Ther 2007; 26: 1063–7.

💊 Preparations

Proprietary Preparations

Arg.: Floxlevo; Grepiflox; Leflumax; Levaquin; Septibiotic; Tavanic; Teraquin; Ultraquin; Uniflox; Valiflox; Austria: Tavanic; Belg.: Tavanic; Braz.: Levaquin; Levotac; Levoxin; Tamiram; Tavanic; Canad.: Levaquin; Chile: Auxxil; Medibiox; Novacilina; Quinobiot; Recamicina; Tavanic; Cz.: Oftaquix; Tavanic; Denm.: Oftaquix; Fin.: Oftaquix; Tavanic; Fr.: Tavanic; Ger.: Oftaquix; Tavanic; Gr.: Tavanic; Hong Kong: Cravit; Hung.: Leflokin; Oftaquix; Tavanic; India: Glevo†; Leeflox; Levocide; Levoff; Levoflox; Lufi; Tavanic; Indon.: Armolev; Cravit; Cravox; Difloxin; Farlev; Lefos; Levocin; Levores; Levovid; Levoxal; Lexa; Lovequin; Mosardal; Nislev; Nufalev; Prolecin; Prolevox; Reskuin; Rinvox; Tevox; Volequin; Voxin; Irl.: Tavanic; Israel: Levo; Tavanic; Ital.: Levoxacin; Oftaquix; Prixar; Tavanic; Jpn: Cravit; Malaysia: Cravit; Glevo; Loxof; Mex.: Elequine; Ran-Levo; Tavanic; Neth.: Oftaquix; Prixar; Tavanic; Philipp.: Floxel; Levox; Oftaquix; Pol.: Oftaquix; Port.: Oftaquix; Tavanic; Rus.: Lefoxin (Лефокцин); Tavanic (Таваник); S.Afr.: Ta va n i c ; Singapore: Cravit; Spain: Tavanic; Swed.: Oftaquix; Tavanic; Switz.: Tavanic; Thai.: Cravit; Lefloxin; Turk.: Cravit; Tavanic; UAE: Jenoquine; UK: Oftaquix; Tavanic; USA: Iquix; Levaquin; Quixin; Venez.: Levaquin; Proxime; Tavanic. Multi-ingredient: India: Levoflox Oz Kit.
Published April 10, 2019.