Jump to content

Levofloxacin: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
AnomieBOT (talk | contribs)
Bots
6,513,010 edits
m Dating maintenance tags: {{Clarify}}
Line 114: Line 114:
Levofloxacin interacts with certain foods and several other drugs leading to undesirable increases or decreases in the serum levels or distribution of one or both drugs.
Levofloxacin interacts with certain foods and several other drugs leading to undesirable increases or decreases in the serum levels or distribution of one or both drugs.


Co-administration of levofloxacin with anti-acids containing magnesium hydroxide or aluminum hydroxide leads to the formation of insoluble salts that are not readily absorbed from the intestinal tract. Peak serum concentrations of ciprofloxacin{{Clarify|date=January 2014}} may be reduced by 90% or more, leading to therapeutic failure. Similar results have been reported when ciprofloxacin{{Clarify|date=January 2014}} is co-administered with iron supplements and multi-vitamins containing zinc.<ref>{{cite journal |author=Rodvold KA, Piscitelli SC |title=New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety |journal=Clin. Infect. Dis. |volume=17 Suppl 1 |issue= |pages=S192–9 | date=August 1993 |pmid=8399914 |doi= |url=}}</ref><ref>{{cite journal |author=Tanaka M, Kurata T, Fujisawa C, ''et al.'' |title=Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide |journal=Antimicrob. Agents Chemother. |volume=37 |issue=10 |pages=2173–8 | date=October 1993 |pmid=8257141 |pmc=192246 |doi= |url=}}</ref>
Co-administration of levofloxacin with anti-acids containing magnesium hydroxide or aluminum hydroxide leads to the formation of insoluble salts that are not readily absorbed from the intestinal tract. Peak serum concentrations of levofloxacin may be reduced by 90% or more, leading to therapeutic failure. Similar results have been reported when levofloxacin is co-administered with iron supplements and multi-vitamins containing zinc.<ref>{{cite journal |author=Rodvold KA, Piscitelli SC |title=New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety |journal=Clin. Infect. Dis. |volume=17 Suppl 1 |issue= |pages=S192–9 | date=August 1993 |pmid=8399914 |doi= |url=}}</ref><ref>{{cite journal |author=Tanaka M, Kurata T, Fujisawa C, ''et al.'' |title=Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide |journal=Antimicrob. Agents Chemother. |volume=37 |issue=10 |pages=2173–8 | date=October 1993 |pmid=8257141 |pmc=192246 |doi= |url=}}</ref>


Unlike ciprofloxacin, levofloxacin does not appear to inhibit the drug metabolizing enzyme [[CYP1A2]], and thus is not expected to strongly interact with [[theophylline]]. It is a weak inhibitor of [[CYP2C9]],<ref>{{cite journal |author=Zhang L, Wei MJ, Zhao CY, Qi HM |title=Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes |journal=Acta Pharmacol. Sin. |volume=29 |issue=12 |pages=1507–14 | date=December 2008 |pmid=19026171 |doi=10.1111/j.1745-7254.2008.00908.x |url=}}</ref> suggesting potential to inhibit the degradation of [[warfarin]] and [[phenprocoumon]]. Data from a case control study suggests that the coadministration of levofloxacin and warfarin increases the risk of hospitalization for gastric bleeding relative to treatment with warfarin alone.<ref>{{cite journal |author=Schelleman H, Bilker WB, Brensinger CM, Han X, Kimmel SE, Hennessy S |title=Warfarin with fluoroquinolones, sulfonamides, or azole antifungals: interactions and the risk of hospitalization for gastrointestinal bleeding |journal=Clin. Pharmacol. Ther. |volume=84 |issue=5 |pages=581–8 | date=November 2008 |pmid=18685566 |pmc=2574587 |doi=10.1038/clpt.2008.150 |url=}}</ref>
Unlike ciprofloxacin, levofloxacin does not appear to inhibit the drug metabolizing enzyme [[CYP1A2]], and thus is not expected to strongly interact with [[theophylline]]. It is a weak inhibitor of [[CYP2C9]],<ref>{{cite journal |author=Zhang L, Wei MJ, Zhao CY, Qi HM |title=Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes |journal=Acta Pharmacol. Sin. |volume=29 |issue=12 |pages=1507–14 | date=December 2008 |pmid=19026171 |doi=10.1111/j.1745-7254.2008.00908.x |url=}}</ref> suggesting potential to inhibit the degradation of [[warfarin]] and [[phenprocoumon]]. Data from a case control study suggests that the coadministration of levofloxacin and warfarin increases the risk of hospitalization for gastric bleeding relative to treatment with warfarin alone.<ref>{{cite journal |author=Schelleman H, Bilker WB, Brensinger CM, Han X, Kimmel SE, Hennessy S |title=Warfarin with fluoroquinolones, sulfonamides, or azole antifungals: interactions and the risk of hospitalization for gastrointestinal bleeding |journal=Clin. Pharmacol. Ther. |volume=84 |issue=5 |pages=581–8 | date=November 2008 |pmid=18685566 |pmc=2574587 |doi=10.1038/clpt.2008.150 |url=}}</ref>

Revision as of 20:13, 4 January 2014

Levofloxacin
Clinical data
Trade namesLevaquin, Tavanic,
Quixin (eye drops)
AHFS/Drugs.comMonograph
MedlinePlusa697040
License data
Routes of
administration		Oral, IV, ophthalmic
ATC code
Legal status
Legal status
  • US: WARNING[1]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability99%
Protein binding24 to 38%
Metabolism<5% desmethyl and N-oxide metabolites
Elimination half-life6 to 8 hours
ExcretionUrinary, mainly unchanged
Identifiers
  • (S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.115.581 Edit this at Wikidata
Chemical and physical data
FormulaC18H20FN3O4
Molar mass361.368 g/mol g·mol−1
3D model (JSmol)
  • C[C@H]1COc2c3n1cc(c(=O)c3cc(c2N4CCN(CC4)C)F)C(=O)O
  • InChI=1S/C18H20FN3O4/c1-10-9-26-17-14-11(16(23)12(18(24)25)8-22(10)14)7-13(19)15(17)21-5-3-20(2)4-6-21/h7-8,10H,3-6,9H2,1-2H3,(H,24,25)/t10-/m0/s1 checkY
  • Key:GSDSWSVVBLHKDQ-JTQLQIEISA-N checkY
 ☒NcheckY (what is this?)  (verify)

Levofloxacin (trade names Levaquin (US), Tavanic (EU), and others) is a broad spectrum antibiotic of the fluoroquinolone drug class,[2][3] and the levo isomer of its predecessor ofloxacin. Its spectrum of activity includes most strains of bacterial pathogens responsible for respiratory, urinary tract, gastrointestinal, and abdominal infections, including Gram negative (Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, and Pseudomonas aeruginosa), Gram positive (methicillin-sensitive but not methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis, Enterococcus faecalis, and Streptococcus pyogenes), and atypical bacterial pathogens (Chlamydophila pneumoniae and Mycoplasma pneumoniae). Compared to earlier antibiotics of the fluoroquinoline class such as ciprofloxacin, levofloxacin exhibits greater activity toward Gram-(+) bacteria[4] but lesser activity toward Gram-(−) bacteria,[5] especially Pseudomonas aeruginosa. Levofloxacin and later generation fluoroquinolones are collectively referred to as "respiratory quinolones" to distinguish them from earlier fluoroquinolones which exhibited modest activity toward the important respiratory pathogen Streptococcus pneumoniae.[6]

Levofloxacin and other fluoroquinolones are valued for their broad spectrum of activity, excellent tissue penetration, and for their availability in both oral and intravenous formulations.[7] Levafloxacin is used alone or in combination with other antibacterial drugs to treat certain bacterial infections including pneumonia,[8] urinary tract infections,[9][10] and abdominal infections.[11]

Levofloxacin and other fluoroquinolones are generally well tolerated, but in rare instances have produced serious adverse reactions such as spontaneous tendon ruptures and irreversible peripheral neuropathy.[12] Tendon damage may manifest months after therapy had been completed. Levofloxacin may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems.[13]

Medical uses

Levofloxacin is used to treat infections including: respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax,[14] endocarditis, meningitis, pelvic inflammatory disease, traveler's diarrhea, tuberculosis and plague.[15]

The drug exhibits enhanced activity against the important respiratory pathogen Streptococcus pneumoniae relative to earlier fluoroquinolone derivatives like ciprofloxacin. For this reason, it is considered a "respiratory fluoroquinolone" along with more recently developed fluoroquinolones such as moxifloxacin and gemifloxacin. It is less active than ciprofloxacin against Gram-(−) bacteria, especially Pseudomonas aeruginosa, and lacks the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of moxifloxacin and gemifloxacin.[4][16][17][18] Levofloxacin has shown moderate activity against anaerobes, and is about twice as potent as ofloxacin against Mycobacterium tuberculosis and other mycobacteria, including Mycobacterium avium complex.[19]

Levofloxacin plays an important role in professional medical society guidelines for the treatment of pneumonia, urinary tract infections, and abdominal infections. The Infectious Disease Society of America (IDSA) and the American Thoracic Society recommend levofloxacin and other respiratory fluoroquinolines as first line treatment for community acquired pneumonia when co-morbidities such an heart, lung, or liver disease are present or when in-patient treatment is required.[8] Levofloxacin also plays an important role in recommended treatment regimens for ventilator-associated and healthcare-associated pneumonia.[20]

It is recommended by the IDSA as a first-line treatment option for catheter-associated urinary tract infections in adults.[21] In combination with metronidazole it is recommended as one of several first-line treatment options for adult patients with community-acquired intra-abdominal infections of mild-to-moderate severity.[11] The IDSA also recommends it in combination with rifampicin as a first-line treatment for prosthetic joint infections.[22] The American Urological Association recommends levofloxacin as a first-line treatment for bacterial prostatitis.[23][24]

Levofloxacin and other fluoroquinolones have also been widely used for the outpatient treatment of uncomplicated community-acquired respiratory and urinary tract infections, indications for which major medical societies generally recommend the use of older, narrower spectrum drugs to avoid fluoroquinolone resistance development. The U.S. Food and Drug Administration (FDA) estimates that over 23 million outpatient prescriptions for fluoroquinolones were filled for fluoroquinolines in the United States in 2011.[25] This indiscriminant use has led to widespread resistance development in common pathogens such as Escherichia coli and Klebsiella pneumoniae. In many countries, resistance rates among healthcare-associated infections with these pathogens now exceeds 20%.[26][27][28]

Levofloxacin is not approved in most countries for the treatment of children except in unique and life-threatening infections because it is associated with a severe risk of severe musculoskeletal injury in this population, a property it shares with other fluoroquinolones. In the United States levofloxacin is approved for the treatment of anthrax and plague in children over six months of age.[29]

Availability

Levofloxacin is available in tablet form, injection, oral solution, as well as used in prescription eye and ear drops.[30]

Use in specific populations

Pregnancy

According to the FDA approved prescribing information, levofloxacin is pregnancy category C.[31] This designation indicates that animal reproduction studies have shown a adverse effects on the fetus and there are no adequate and well-controlled studies in humans, but the potential benefit to the mother may in some cases outweigh the risk to the fetus. Other flouroquinolones have also been reported as being present in the mother's milk and are passed on to the nursing child.[32][33]

Children

Oral and intravenous levofloxacin are not licensed for use in children, except as noted above, due to the risk of musculoskeletal injury. In one study,[34][35] 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, serious adverse events were experienced by 6% of those treated with levofloxacin and 4% of those treated with comparator antibiotics. Most of these were considered by the treating physician to be unrelated or doubtfully related to the study drug. 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.[36]

Contraindications

Levofloxacin 750 mg IV

Package inserts mention that levofloxacin is to be avoided in patients with a known hypersensitivity to levofloxacin or other quinolone drugs,[30] and that caution should be exercised in prescribing to patients with liver disease.[37][38]

Levofloxacin is also considered to be contraindicated in patients with epilepsy or other seizure disorders, and in patients who have a history of quinolone-associated tendon rupture.[37]

Adverse effects

Most adverse reactions are mild to moderate; however, sometimes serious adverse effects occur. There is some disagreement in the medical literature regarding whether and to what extent levofloxacin and other fluoroquinolones produce serious adverse effects more frequently than other broad spectrum antibacterial drugs.[39][40][41][42]

In pooled results from 7537 patients exposed to levofloxcacin in 29 clinical trials, 4.3% discontinued treatment due to adverse drug reactions. The most common adverse reactions leading to discontinuation were gastrointestinal, including nausea, vomiting, and constipation. Overall, 7% of patients experienced nausea, 6% headache, 5% diarrhea, 4% insomnia, along with other adverse reactions experienced at lower rates.[43]

Other less common but serious adverse effects have been observed both in clinical trials as well as in reviews of post-approval spontaneous adverse event reports. Prominent among these is the potential for tendon damage, including rupture of the Achilles tendon, which is the subject of a black box warning in the official prescribing informations for all fluoroquinolones in the United States. Injury, including tendon rupture, has been observed up to 6 months after cessation of treatment; the elderly, transplant patients, and those with a current or historical corticosteroid use are at elevated risk.[44] A population-based study in the Netherlands estimated that between 1 and 15 fluoroquinolone-attributable tendon ruptures resulted from 318,000 fluoroquinoline prescriptions in 1996. A detailed overview of risk factors for fluoroquinolone-associated tendon rupture has been published; advanced age, concurrent treatment with corticosteroids, and higher doses of fluoroquinolone appear to be the most important risk factors.[45] The U.S. label for levofloxacin also contains a black box warning for the exacerbation of the symptoms of the neurological disease myasthenia gravis.[46]

A wide variety of other uncommon but serious adverse events have been associated with fluoroquinolone use, with varying degrees of evidence supporting causation. These include irreversible peripheral neuropathy, anaphylaxis, hepatotoxicity, central nervous system effects including seizures and psychiatric effects, prolongation of the QT interval, blood glucose disturbances, and photosensitivity, among others.[43] Levofloxacin may produce fewer of these rare serious adverse effects than other fluoroquinolones.[47]

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.[48]

Overdose

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.[30]

Interactions

Levofloxacin interacts with certain foods and several other drugs leading to undesirable increases or decreases in the serum levels or distribution of one or both drugs.

Co-administration of levofloxacin with anti-acids containing magnesium hydroxide or aluminum hydroxide leads to the formation of insoluble salts that are not readily absorbed from the intestinal tract. Peak serum concentrations of levofloxacin may be reduced by 90% or more, leading to therapeutic failure. Similar results have been reported when levofloxacin is co-administered with iron supplements and multi-vitamins containing zinc.[49][50]

Unlike ciprofloxacin, levofloxacin does not appear to inhibit the drug metabolizing enzyme CYP1A2, and thus is not expected to strongly interact with theophylline. It is a weak inhibitor of CYP2C9,[51] suggesting potential to inhibit the degradation of warfarin and phenprocoumon. Data from a case control study suggests that the coadministration of levofloxacin and warfarin increases the risk of hospitalization for gastric bleeding relative to treatment with warfarin alone.[52]

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in combination with high dose fluoroquinolone therapy may lead to seizures.[53]

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 two type II topoisomerase enzymes, namely DNA gyrase and topoisomerase IV.[54] 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 responsibe for supercoiling the DNA, so that it will fit in the newly formed cells. Both mechanisms amount to killing the bacterium, that is, levofloxacin acts as a bactericide.[55]

Chemical properties

Levofloxacin is the levo isomer of the racemate ofloxacin, another quinolone antimicrobial agent. In layman terms, this means that levofloxacin is the 50% of ofloxacin that have found to be effective agains bacteria, while the other 50% have been removed. As a consequence, levofloxacin dosing is half that of ofloxacin. In chemical terms, levofloxacin, a chiral fluorinated carboxyquinolone, is the pure (−)-(S)-enantiomer of the racemic ofloxacin.[56]

The substance is used as the hemihydrate, which has the empirical formula C18H20FN3O4 · ½ H2O and a molecular mass of 370.38 g/mol. Levofloxacin is a light-yellowish-white to yellow-white crystal or crystalline powder.[30]

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.[43]

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.

History

Levofloxacin is marketed by Sanofi-Aventis under the trade name "Tavanic".[57] Levaquin is also marketed worldwide for oral and IV use, as well as used in ophthalmic solutions. Daiichi Sankyo had granted an exclusive license to Sanofi-Aventis to make, use and sell pharmaceutical preparations containing levofloxacin in the UK and Mexico.[58] Other manufacturers include Novell Pharmaceutical Laboratories (Levores).

Levofloxacin was first patented in 1987 (Levofloxacin European patent – Daiichi Pharmaceutical Co., Ltd.) and was approved by the United States Food and Drug Administration on 20 December 1996 for use in the United States to treat bacterial sinusitus, bacterial exacerbations of bronchitis, community-acquired pneumonia, uncomplicated skin infections, complicated urinary tract infections, and acute pyelonephritis.[59]

The current United States patent is held by Ortho-McNeil-Janssen.[60] Ranked 19th in world sales in 2007, sales for Levaquin exceeded $1.4 billion.[60] Levaquin was the most prescribed fluoroquinolone drug in the world for 2007.[61]

In addition, generic versions of levofloxacin had been available since 2004 and marketed as a generic drug under a variety of different brand names. However, Daiichi Sankyo-Johnson and Johnson-Ortho McNeil filed numerous patent lawsuits to prevent such generic equivalents from being marketed, claiming that their patent did not expire until 23 June 2009.[62] see Generic equivalents

Society and culture

Regulatory history in the United States

Levofloxacin was first patented in 1987, and was subsequently approved for use in Japan (1 October 1993), Korea (4 April 1994), Hong Kong (3 October 1994), and China (3 May 1995). Levofloxacin received FDA approval in the United States 20 December 1996. Its predecessor Floxin (ofloxacin) was patented in 1982 (European patent, Daiichi Sankyo) and received FDA approval 28 December 1990. The U.S. patent is owned by Daiichi Sankyo and exclusively licensed to Ortho-McNeil.[59][63]

Many of the clinical isolates that were initially tested within the NDA for levofloxacin against ofloxacin disks instead of levofloxacin disks but reported as susceptible or resistant to levofloxacin. When levofloxacin disks were not available in early clinical trials, a 5-pg ofloxacin disk was substituted. The FDA medical reviewers considered the two drugs to be one and the same and hence interchangeable.[59]

The FDA requested updating the carton and container labels to include a statement to let dispensers know that a Medication Guide must be dispensed with the product, in compliance with the Medication Guide Regulations as specified in 21 CFR 208.24 (d).

Issuance of a Medication Guide and revisions to include new safety information. The FDA has determined that levofloxacin poses a serious and significant public health concern, requiring the distribution of a Medication Guide. However the Medication Guide does not include any boxed warnings.[66]

Litigation

There are cases currently pending before the United States District Court, District of Minnesota, involving Levaquin. On 13 June 2008, a Judicial Panel On Multidistrict Litigation (MDL) granted the Plaintiffs' motion to centralize individual and class action lawsuits involving Levaquin in the District of Minnesota over objection of Defendants, Johnson and Johnson / Ortho McNeil.[67]

On 6 July 2009, The New Jersey Supreme Court had also designated litigation over Levaquin as a mass tort and has assigned it to an Atlantic County, N.J., judge. The suits charge that the drug has caused achilles tendon ruptures and other permanent damage.[68][69] Additional lawsuits have also been filed in the Illinois State Court. Of a total of about 3400 cases, 845 were settled out of court after Johnson and Johnson prevailed in three of the first four cases to go to trial[70][71]

A complaint has been filed by The US Justice Department with a Federal Court in Boston (January 2010) accusing Johnson and Johnson of illegally paying millions of dollars in kickbacks to Omnicare, one of the nation's largest pharmacies specializing in nursing home patients. In return, Omnicare allegedly nearly tripled its annual purchase of Johnson and Johnson's products; including Levaquin.

On 8 April 2010 in the Beaumont Division of the Eastern District of Texas, a class action lawsuit was filed by Lisa Presley on behalf of herself and others similar situated against Johnson and Johnson, Ortho-McNeil Pharmaceuticals Inc. and Johnson and Johnson Pharmaceutical Research and Development LLC. (Case No 1:10cv00200.)[72]

The various manufacturers have countered these allegations stating that they believe that these drugs are both safe and effective antibiotics, well tolerated with a minimum of side-effects, that such reactions are rare and the benefits of such therapy outweigh the perceived risks.

Research

Levofloxacin can be used effectively as a positive control in thorough QT/QTc studies in healthy volunteers and can fulfil the criteria for a positive comparator. The ICH E14 guidelines recommend a threshold of around 5 ms for a positive QT/QTc study. The largest time-matched difference in QTc for levofloxacin suggests the potential for use in more rigorous QT/QTc studies.[73]

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  2. ^ Nelson, JM.; Chiller, TM.; Powers, JH.; Angulo, FJ. (April 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.
  3. ^ Kawahara, S. (December 1998). "[Chemotherapeutic agents under study]". Nippon Rinsho. 56 (12): 3096–9. PMID 9883617.
  4. ^ a b Lafredo SC, Foleno BD, Fu KP (1993). "Induction of resistance of Streptococcus pneumoniae to quinolones in vitro". Chemotherapy. 39 (1): 36–9. PMID 8383031.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Yamane N, Jones RN, Frei R, Hoban DJ, Pignatari AC, Marco F (April 1994). "Levofloxacin in vitro activity: results from an international comparative study with ofloxacin and ciprofloxacin". J Chemother. 6 (2): 83–91. PMID 8077990.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ Wispelwey B, Schafer KR (November 2010). "Fluoroquinolones in the management of community-acquired pneumonia in primary care". Expert Rev Anti Infect Ther. 8 (11): 1259–71. doi:10.1586/eri.10.110. PMID 21073291.
  7. ^ Laurence Brunton; John Lazo; Keith Parker (23 August 2005). Goodman & Gilman's The Pharmacological Basis of Therapeutics. McGraw-Hill Prof Med/Tech. ISBN 978-0-07-142280-2. Retrieved 30 October 2012.
  8. ^ a b Mandell LA, Wunderink RG, Anzueto A; et al. (March 2007). "Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults". Clin. Infect. Dis. 44 Suppl 2: S27–72. doi:10.1086/511159. PMID 17278083. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  9. ^ "www.uroweb.org" (PDF).
  10. ^ "National Guideline Clearinghouse | Treatment of urinary tract infections in nonpregnant women".
  11. ^ a b Solomkin JS, Mazuski JE, Bradley JS; et al. (January 2010). "Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America". Clin. Infect. Dis. 50 (2): 133–64. doi:10.1086/649554. PMID 20034345. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  12. ^ http://www.fda.gov/Drugs/DrugSafety/ucm365050.htm
  13. ^ label
  14. ^ Renata Albrecht (24 November 2004). "NDA 20-634/S-035, NDA 20-635/S-035, NDA 21-721/S-003" (PDF). U.S. Food and Drug Administration (FDA).
  15. ^ "Levofloxacin". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  16. ^ Fu KP, Lafredo SC, Foleno B; et al. (April 1992). "In vitro and in vivo antibacterial activities of levofloxacin (l-ofloxacin), an optically active ofloxacin". Antimicrob. Agents Chemother. 36 (4): 860–6. PMC 189464. PMID 1503449. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  17. ^ Blondeau JM (May 1999). "A review of the comparative in-vitro activities of 12 antimicrobial agents, with a focus on five new respiratory quinolones'". J. Antimicrob. Chemother. 43 Suppl B: 1–11. PMID 10382869.
  18. ^ Cormican MG, Jones RN (January 1997). "Antimicrobial activity and spectrum of LB20304, a novel fluoronaphthyridone". Antimicrob. Agents Chemother. 41 (1): 204–11. PMC 163688. PMID 8980783.
  19. ^ John A. Bosso (1998). "New and Emerging Quinolone Antibiotics". Journal of Infectious Disease Pharmacotherapy. 2 (4): 61–76. doi:10.1300/J100v02n04_06. ISSN 1068-7777.
  20. ^ File TM (August 2010). "Recommendations for treatment of hospital-acquired and ventilator-associated pneumonia: review of recent international guidelines". Clin. Infect. Dis. 51 Suppl 1: S42–7. doi:10.1086/653048. PMID 20597671.
  21. ^ Hooton TM, Bradley SF, Cardenas DD; et al. (March 2010). "Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America". Clin. Infect. Dis. 50 (5): 625–63. PMID 20175247. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  22. ^ Osmon DR, Berbari EF, Berendt AR; et al. (January 2013). "Executive summary: diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America". Clin. Infect. Dis. 56 (1): 1–10. doi:10.1093/cid/cis966. PMID 23230301. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  23. ^ "www.uroweb.org" (PDF).
  24. ^ Schaeffer AJ (September 2004). "NIDDK-sponsored chronic prostatitis collaborative research network (CPCRN) 5-year data and treatment guidelines for bacterial prostatitis". Int. J. Antimicrob. Agents. 24 Suppl 1: S49–52. doi:10.1016/j.ijantimicag.2004.02.009. PMID 15364307.
  25. ^ "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".
  26. ^ "Antimicrobial resistance interactive database (EARS-Net)".
  27. ^ "www.ecdc.europa.eu" (PDF).
  28. ^ "www.cdc.gov" (PDF).
  29. ^ Renata Albrecht (5 May 2008). "NDA 20-634/S-047, NDA 20-635/S-051, NDA 21-721/S-015" (PDF). U.S. Food and Drug Administration (FDA).
  30. ^ a b c d Janssen Pharmaceutica (2008). "Highlights of Prescribing Information" (PDF). U.S. Food and Drug Administration (FDA). {{cite web}}: Unknown parameter |month= ignored (help)
  31. ^ Levaquin (levofloxacin) Label
  32. ^ Shin HC, Kim JC, Chung MK (September 2003). "Fetal and maternal tissue distribution of the new fluoroquinolone DW-116 in pregnant rats". Comp. Biochem. Physiol. C Toxicol. Pharmacol. 136 (1): 95–102. doi:10.1016/j.cca.2003.08.004. PMID 14522602.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  33. ^ Dan M, Weidekamm E, Sagiv R, Portmann R, Zakut H (February 1993). "Penetration of fleroxacin into breast milk and pharmacokinetics in lactating women". Antimicrob. Agents Chemother. 37 (2): 293–6. doi:10.1128/AAC.37.2.293. PMC 187655. PMID 8452360.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  34. ^ "www.accessdata.fda.gov" (PDF).
  35. ^ Noel GJ, Bradley JS, Kauffman RE (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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  36. ^ "www.fda.gov" (PDF).
  37. ^ a b Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 7961–7. ISBN 978-3-85200-181-4.
  38. ^ Coban S, Ceydilek B, Ekiz F, Erden E, Soykan I (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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  39. ^ Liu HH (May 2010). "Safety profile of the fluoroquinolones: focus on levofloxacin". Drug Saf. 33 (5): 353–69. doi:10.2165/11536360-000000000-00000. PMID 20397737.
  40. ^ Karageorgopoulos DE, Giannopoulou KP, Grammatikos AP, Dimopoulos G, Falagas ME (March 2008). "Fluoroquinolones compared with beta-lactam antibiotics for the treatment of acute bacterial sinusitis: a meta-analysis of randomized controlled trials". CMAJ. 178 (7): 845–54. doi:10.1503/cmaj.071157. PMC 2267830. PMID 18362380.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  41. ^ Lipsky BA, Baker CA (February 1999). "Fluoroquinolone toxicity profiles: a review focusing on newer agents". Clin. Infect. Dis. 28 (2): 352–64. doi:10.1086/515104. PMID 10064255.
  42. ^ Stahlmann R, Lode HM (July 2013). "Risks associated with the therapeutic use of fluoroquinolones". Expert Opin Drug Saf. 12 (4): 497–505. doi:10.1517/14740338.2013.796362. PMID 23651367.
  43. ^ a b c "www.accessdata.fda.gov" (PDF).
  44. ^ Khaliq Y, Zhanel GG (June 2003). "Fluoroquinolone-associated tendinopathy: a critical review of the literature". Clin. Infect. Dis. 36 (11): 1404–10. doi:10.1086/375078. PMID 12766835.
  45. ^ 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.
  46. ^ Jones SC, Sorbello A, Boucher RM (October 2011). "Fluoroquinolone-associated myasthenia gravis exacerbation: evaluation of postmarketing reports from the US FDA adverse event reporting system and a literature review". Drug Saf. 34 (10): 839–47. doi:10.2165/11593110-000000000-00000. PMID 21879778.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  47. ^ Carbon C (2001). "Comparison of side effects of levofloxacin versus other fluoroquinolones". Chemotherapy. 47 Suppl 3: 9–14, discussion 44–8. doi:10.1159/000057839. PMID 11549784.
  48. ^ Vardakas KZ, Konstantelias AA, Loizidis G, Rafailidis PI, Falagas ME (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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  49. ^ Rodvold KA, Piscitelli SC (August 1993). "New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety". Clin. Infect. Dis. 17 Suppl 1: S192–9. PMID 8399914.
  50. ^ Tanaka M, Kurata T, Fujisawa C; et al. (October 1993). "Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide". Antimicrob. Agents Chemother. 37 (10): 2173–8. PMC 192246. PMID 8257141. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  51. ^ Zhang L, Wei MJ, Zhao CY, Qi HM (December 2008). "Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes". Acta Pharmacol. Sin. 29 (12): 1507–14. doi:10.1111/j.1745-7254.2008.00908.x. PMID 19026171.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  52. ^ Schelleman H, Bilker WB, Brensinger CM, Han X, Kimmel SE, Hennessy S (November 2008). "Warfarin with fluoroquinolones, sulfonamides, or azole antifungals: interactions and the risk of hospitalization for gastrointestinal bleeding". Clin. Pharmacol. Ther. 84 (5): 581–8. doi:10.1038/clpt.2008.150. PMC 2574587. PMID 18685566.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  53. ^ Domagala JM (April 1994). "Structure-activity and structure-side-effect relationships for the quinolone antibacterials". J. Antimicrob. Chemother. 33 (4): 685–706. doi:10.1093/jac/33.4.685. PMID 8056688.
  54. ^ Drlica K, Zhao X (1 September 1997). "DNA gyrase, topoisomerase IV, and the 4-quinolones". Microbiol Mol Biol Rev. 61 (3): 377–92. PMC 232616. PMID 9293187.
  55. ^ Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. p. 814f. ISBN 3-8047-1763-2.
  56. ^ Morrissey, I.; Hoshino, K.; Sato, K.; Yoshida, A.; Hayakawa, I.; Bures, MG.; Shen, LL. (August 1996). "Mechanism of differential activities of ofloxacin enantiomers" (PDF). Antimicrob Agents Chemother. 40 (8): 1775–84. PMC 163416. PMID 8843280.
  57. ^ University of Maryland Medical Center. "Levofloxacin". USA: University of Maryland.
  58. ^ Takashi Shoda (23 October 2008). "UK Levofloxacin SPC and Underlying Patent Upheld by High Court Patent Court". USA: Daiichi Sankyo, Limited.[dead link‍]
  59. ^ a b c "www.accessdata.fda.gov" (PDF).
  60. ^ a b "LEVAQUIN". USA: drugpatentwatch.com.
  61. ^ Ed Lamb (1 May 2008). "Top 200 Prescription Drugs of 2007". Pharmacy Times. Retrieved 21 July 2009.[dead link‍]
  62. ^ "Novopharm Limited". USA. 3 November 2009. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  63. ^ JOHNSON & JOHNSON (28 March 2004). "UNITED STATES SECURITIES AND EXCHANGE COMMISSION". USA: shareholder.com. pp. 28–29.
  64. ^ "NDA 20-634/S-054, NDA 20-635/S-059, NDA 21-721/S-022" (PDF). U.S. Food and Drug Administration (FDA). 12 March 2009. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  65. ^ Ozlem Belen (27 March 2009). "NDA 20-634/S-053, NDA 20-635/S-058, NDA 21-721/S-021" (PDF). U.S. Food and Drug Administration (FDA).
  66. ^ Ortho-McNeil-Janssen Pharmaceuticals, Inc. (October 2008). "FDA-Approved Medication Guide" (PDF). U.S. Food and Drug Administration (FDA).
  67. ^ "Levaquin MDL | 08-MD-1943". USA: US District Court District of Minnesota. Retrieved 7 September 2009.
  68. ^ Charles Toutant (6 July 2009). "Litigation Over Johnson & Johnson Antibiotic Levaquin Designated N.J. Mass Tort". New Jersey Law Journal.
  69. ^ Reed Abelson (14 October 2011). "Johnson & Johnson Wins Suit Over Antibiotic's Side Effects". The New York Times. {{cite news}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  70. ^ "Levaquin MDL | United States District Court – District of Minnesota, United States District Court – District of Minnesota".
  71. ^ "Johnson & Johnson Settles 845 Levaquin Lawsuits – Businessweek".
  72. ^ The Southeast Texas Record. 17 April 2010 S.E. Texas' Legal Journal Class action alleges antibiotic causes tendon damage 15 April 2010 8:21 am By Michelle Massey, East Texas Bureau http://www.setexasrecord.com/news/226050-class-action-alleges-antibiotic-causes-tendon-damage
  73. ^ Taubel, Jorg (November 2009). "Levofloxacin can be used effectively as a positive control in thorough QT/QTc studies in healthy volunteers" (PDF). British Journal of Clinical Pharmacology. 69 (4): 391–400. doi:10.1111/j.1365-2125.2009.03595.x. PMC 2848412. PMID 20406223. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
Retrieved from "https://en.wikipedia.org/w/index.php?title=Levofloxacin&oldid=589184405"