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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/08 17:34:05」(JST)

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Levofloxacin, sold under the trade names Levaquin and Tavanic, among others is an antibiotic.^[1] It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, urinary tract infections, chronic prostatitis, and some types of gastroenteritis. Along with other antibiotics it may be used to treat tuberculosis, meningitis, or pelvic inflammatory disease. It is available by mouth or intravenously.^[1]

Common side effects include nausea, diarrhea, and trouble sleeping. Serious side effects may include tendon rupture, tendon inflammation, seizures, psychosis, and potentially permanent peripheral nerve damage. Tendon damage may appear months after treatment is completed. People may also sunburn more easily. In people with myasthenia gravis muscle weakness and breathing problems may worsen.^[1] The risk of use during pregnancy is low and it is probably okay during breastfeeding. Levofloxacin is a broad-spectrum antibiotic of the fluoroquinolone drug class.^[2] It usually results in death of the bacteria.^[1] It is the left sided isomer of the medication ofloxacin.^[2]

Levofloxacin was approved for medical use in the United States in 1996.^[1] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.^[3] It is available as a generic medication.^[1] The wholesale cost is about 0.44 to 0.95 USD per week of treatment.^[4] In the United States a week of treatment cost about 50 to 100 USD.^[5]

1 Medical uses
- 1.1 Pregnancy
- 1.2 Children
- 1.3 Spectrum of activity
- 1.4 Availability
2 Contraindications
3 Adverse effects
4 Overdose
5 Interactions
6 Mechanism of action
7 Chemical properties
8 Pharmacokinetics
9 History
10 Usage
11 Litigation
- 11.1 Class action
12 Research
13 References
14 External links

Medical uses

Levofloxacin is used to treat infections including: respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax,^[6] endocarditis, meningitis, pelvic inflammatory disease, traveler's diarrhea, tuberculosis and plague.^[7]

Levofloxacin is used 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 as 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.^[9]

It is recommended by the IDSA as a first-line treatment option for catheter-associated urinary tract infections in adults.^[10] 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.^[12] The American Urological Association recommends levofloxacin as a first-line treatment for bacterial prostatitis.^[13]^[14]

Levofloxacin and other fluoroquinolones have also been widely used for the 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. Due to its widespread use, common pathogens such as Escherichia coli and Klebsiella pneumoniae have developed resistance. In many countries, resistance rates among healthcare-associated infections with these pathogens now exceeds 20%.^[15]^[16]^[17]

Pregnancy

According to the FDA approved prescribing information, levofloxacin is pregnancy category C.^[18] This designation indicates that animal reproduction studies have shown 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 fluoroquinolones have also been reported as being present in the mother's milk and are passed on to the nursing child.^[19]^[20]

Children

Levofloxacin is not approved in most countries for the treatment of children except in unique and life-threatening infections because it is associated with an elevated risk of 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.^[21]

Levofloxacin is recommended by the Pediatric Infectious Disease Society and the Infectious Disease Society of America as a first-line treatment for pediatric pneumonia caused by penicillin-resistant Streptococcus pneumoniae, and as a second-line agent for the treatment of penicillin-sensitive cases.^[22]

In one study,^[23]^[24] 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.^[25]

Spectrum of activity

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.^[26]

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-negative bacteria, especially Pseudomonas aeruginosa, and lacks the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of moxifloxacin and gemifloxacin.^[27]^[28]^[29]^[30] 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.^[31]

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 towards Gram-positive bacteria^[27] but lesser activity toward Gram-negative bacteria,^[32] especially Pseudomonas aeruginosa.

Availability

Levofloxacin and NaCl injection, specification is 100mL / 750mg

Levofloxacin is available in tablet form, injection, oral solution, as well as used in prescription eye and ear drops.^[33]

Contraindications

Package inserts mention that levofloxacin is to be avoided in patients with a known hypersensitivity to levofloxacin or other quinolone drugs,^[33] and that caution should be exercised in prescribing to patients with liver disease.^[34]^[35]

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.^[34]

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.^[36]^[37]^[38]^[39]

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.^[40]

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.^[41] 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.^[42] The U.S. label for levofloxacin also contains a black box warning for the exacerbation of the symptoms of the neurological disease myasthenia gravis.^[43]

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.^[40] Levofloxacin may produce fewer of these rare serious adverse effects than other fluoroquinolones.^[44]

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.^[45]

The U.S. FDA requires a black box warning for levofloxacin, pertaining to peripheral nerve damage.^[46]

Overdose

Overdosing experiments in animals showed central effects such as dizziness, confusion and seizures, as well as prolongation of the QT interval and gastrointestinal disorders.^[34]

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.^[33]

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.

When levofloxacin is taken with anti-acids containing magnesium hydroxide or aluminum hydroxide, the two combine to form insoluble salts that are difficult to absorb from the intestines. Peak serum concentrations of levofloxacin may be reduced by 90% or more, which can prevent the levofloxacin from working. Similar results have been reported when levofloxacin is taken with iron supplements and multi-vitamins containing zinc.^[47]^[48]

Unlike ciprofloxacin, levofloxacin does not appear to deactivate the drug metabolizing enzyme CYP1A2. Therefore, drugs that use that enzyme, like theophylline, do not interact with levofloxacin. It is a weak inhibitor of CYP2C9,^[49] suggesting potential to block the breakdown of warfarin and phenprocoumon. This can result in more action of drugs like warfarin, leading to more potential side effects, such as bleeding.^[50]

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in combination with high dose fluoroquinolone therapy may lead to seizures.^[51]

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.^[52] 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, that is, levofloxacin acts as a bactericide.^[53]

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 been found to be effective against bacteria, while the other 50% have been removed. In chemical terms, levofloxacin, a chiral fluorinated carboxyquinolone, is the pure (−)-(S)-enantiomer of the racemic ofloxacin.^[54]^[55]

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.^[33]

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.^[40]

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 contains the same main active ingredient as ofloxacin. Within the New Drug Application (NDA) for levofloxacin it was stated that:

“...pre- NDA discussions with the applicant suggested quite strongly that levofloxacin is conceptually identical to ofloxacin. For ofloxacin, the dominant active drug substance is its 1- isomer, which is levofloxacin. Conceptually, this premise should lead to microbiological labeling essentially identical to ofloxacin... the applicant provided various basic studies in support of levofloxacin that had been actually performed using ofloxacin instead of levofloxacin. Particularly, some of the studies on mechanisms of action and the related resistance mechanisms were recapitulated from ofloxacin data rather than being generated anew for levofloxacin...."^[56]

Levofloxacin is marketed by Sanofi-Aventis under the trade name "Tavanic" in Europe, Africa, the Middle East and South America, and by the Ortho-McNeil Pharmaceuticals subsidiary of Johnson and Johnson in the United States.^[57]^[58]

Levofloxacin was first patented in 1987 (Levofloxacin European patent by 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 term of the levofloxacin United States patent was extended by the U.S. Patent and Trademark Office under the provisions of the Hatch Waxman Amendment. Under the terms of Hatch-Waxman, the patent terms of pharmaceutical products that contain a novel active ingredient are extended by up to five years to compensate the developer for the patent life lost while performing clinical trials and other activities required to fulfill regulatory requirements. This extension was challenged by generic drug manufacturer Lupin Pharmaceuticals who argued that since levofloxacin is a single isomer of the previously approved antibacterial ofloxacin, it is not a "novel active ingredient" and thus ineligible for patent term extension. The federal patent court ruled in favor of Ortho McNeil, and generic versions of levofloxacin did not enter the U.S. market until 2009.^[60]

Usage

The U.S. Food and Drug Administration (FDA) estimates that over 23 million outpatient prescriptions for fluoroquinolones were filled in the United States in 2011.^[61]

Litigation

Class action

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^[62] and about 1500 pending at a district court in New Jersey.^[63]^[64]

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.^[64]^[65]^[66]

Research

Levofloxacin can be used effectively as a positive control in thorough QT/QTc studies in healthy volunteers. It can fulfill the criteria for a positive comparator, meaning in studies that require the target to have a long QT interval, it can be given to create such an interval in normally healthy individuals. The ICH E14 guidelines recommend a threshold of around 5 ms for a positive QT/QTc study. Studies have shown that levofloxacin causes a QT lengthening that is above this threshold, indicating its potential use in QT/QTc studies.^[67]

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^ Judge John R. Tunheim. "Levaquin MDL". USA: US Courts. Retrieved 7 September 2009.
^ Charles Toutant (6 July 2009). "Litigation Over Johnson & Johnson Antibiotic Levaquin Designated N.J. Mass Tort". New Jersey Law Journal.
^ ^a ^b Margaret Cronin Fisk and Beth Hawkins for Bloomberg News. Nov 1, 2012 Johnson & Johnson Settles 845 Levaquin Lawsuits
^ "Johnson & Johnson Settles 845 Levaquin Lawsuits - Businessweek".
^ "Levaquin MDL | United States District Court - District of Minnesota, United States District Court - District of Minnesota".
^ Taubel J, Naseem A, Harada T, Wang D, Arezina R, Lorch U, Camm AJ (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.

External links

Levofloxacin at DMOZ
U.S. National Library of Medicine: Drug Information Portal – Levofloxacin
Levaquin Package Insert
Iquix Package Insert
Quixin Package Insert

UpToDate Contents

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1. 経膣メッシュ曝露と骨盤手術後の疼痛のマネージメント management of transvaginal mesh exposure and pain following pelvic surgery
2. 成人における市中肺炎の治療に関する抗菌薬の研究 antibiotic studies for the treatment of community acquired pneumonia in adults
3. Antimicrobial approach to intra-abdominal infections in adults
4. フルオロキノロン類 fluoroquinolones
5. 急性複雑性膀胱炎および腎盂腎炎 acute complicated cystitis and pyelonephritis

English Journal

Dispersive liquid-liquid microextraction combined with ultra-high performance liquid chromatography for the simultaneous determination of 25 sulfonamide and quinolone antibiotics in water samples.

Herrera-Herrera AV, Hernández-Borges J, Borges-Miquel TM, Rodríguez-Delgado MÁ.SourceDepartamento de Química Analítica, Nutrición y Bromatología, Facultad de Química, Universidad de La Laguna (ULL), Avenida Astrofísico Francisco Sánchez, s/n°, 38206 La Laguna (Tenerife), Spain.
Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2013 Mar 5;75:130-7. doi: 10.1016/j.jpba.2012.11.026. Epub 2012 Nov 23.
In this work, a dispersive liquid-liquid microextraction (DLLME) procedure combined with ultra-high performance liquid chromatography with diode-array detection was developed to determine 25 antibiotics in mineral and run-off waters. Optimum DLLME conditions (5mL of water at pH=7.6, 20% (w/v) NaCl,
PMID 23246932

High Prevalence of Fluoroquinolone-Resistant Group B Streptococci among Clinical Isolates in China and Predominance of Sequence Type 19 with Serotype III.

Wang H, Zhao C, He W, Zhang F, Zhang L, Cao B, Sun Z, Xu Y, Yang Q, Mei Y, Hu B, Chu Y, Liao K, Yu Y, Hu Z, Ni Y.SourceDepartment of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2013 Mar;57(3):1538-41. doi: 10.1128/AAC.02317-12. Epub 2013 Jan 7.
A total of 146 group B streptococcus isolates from 8 cities across China belonged to four serotypes. Serotype Ia was more common in children. A high prevalence of resistance was observed for levofloxacin (37.7%), erythromycin (71.2%), clindamycin, (53.4%), and tetracycline (81.5%). The levofloxacin
PMID 23295933

Japanese Journal

Application of Deep Eutectic Solvents in Hybrid Molecularly Imprinted Polymers and Mesoporous Siliceous Material for Solid-Phase Extraction of Levofloxacin from Green Bean Extract

Analytical Sciences 33(5), 611-617, 2017-05
NAID 40021195856

女性急性単純性膀胱炎における尿培養分離菌および抗菌薬感受性の検討

泌尿器科紀要 = Acta urologica Japonica 63(5), 189-193, 2017-05
NAID 120006312218

レボフロキサシンの副作用による両側アキレス腱断裂の一例

整形外科と災害外科 66(2), 244-246, 2017
NAID 130005632144

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★リンクテーブル★

リンク元	「レボフロキサシン」

「レボフロキサシン」

Levofloxacin
Systematic (IUPAC) name
	(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
Clinical data
Trade names	Levaquin, Tavanic, Iquix, others
AHFS/Drugs.com	monograph
MedlinePlus	a697040
Licence data	US FDA:link
Pregnancy; category	US: C (Risk not ruled out); ;
Legal status	℞ (Prescription only);
Routes of; administration	By mouth, IV, eye drops
Pharmacokinetic data
Bioavailability	99%
Protein binding	24 to 38%
Metabolism	<5% desmethyl and N-oxide metabolites
Biological half-life	6 to 8 hours
Excretion	Urinary, mainly unchanged
Identifiers
CAS Number	100986-85-4
ATC code	J01MA12 S01AE05
PubChem	CID 149096
DrugBank	DB01137
ChemSpider	131410
UNII	RIX4E89Y14
KEGG	D08120
ChEMBL	CHEMBL33
NIAID ChemDB	002307
Chemical data
Formula	C18H20FN3O4
Molar mass	361.368 g/mol
	SMILES C[C@H]1COc2c3n1cc(c(=O)c3cc(c2N4CCN(CC4)C)F)C(=O)O ;
	InChI 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 ; Key:GSDSWSVVBLHKDQ-JTQLQIEISA-N ;
(what is this?) (verify)

　　[★]

英: levofloxacin, LVFX
化: レボフロキサシン水和物
商: クラビット、IQUIX、LEVAQUIN、QUIXIN
関: オフロキサシン、抗菌薬

フルオロキノロン系抗菌薬
クラビット点眼液0.5%(参天製薬)に配合されている
医学ノートに詳しい

併用注意

レボフロキサシン錠100mg「BT」添付文書

薬剤名等　フェニル酢酸系又はプロピオン酸系非ステロイド性消炎鎮痛薬　→　非ステロイド性抗炎症薬：フェニル酢酸系のジクロフェナク、プロピオン酸系のロキソプロフェンは使いづらい。

フルルビプロフェン等

臨床症状・措置方法

痙攣を起こすおそれがある。

機序・危険因子

中枢神経におけるGABAA受容体への結合阻害が増強されると考えられている。

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[mnd.uscourts.gov-62] Judge John R. Tunheim. "Levaquin MDL". USA: US Courts. Retrieved 7 September 2009.

[63] Charles Toutant (6 July 2009). "Litigation Over Johnson & Johnson Antibiotic Levaquin Designated N.J. Mass Tort". New Jersey Law Journal.

[Bloomberg2012-64] Margaret Cronin Fisk and Beth Hawkins for Bloomberg News. Nov 1, 2012 Johnson & Johnson Settles 845 Levaquin Lawsuits

[65] "Johnson & Johnson Settles 845 Levaquin Lawsuits - Businessweek".

[66] "Levaquin MDL | United States District Court - District of Minnesota, United States District Court - District of Minnesota".

[67] Taubel J, Naseem A, Harada T, Wang D, Arezina R, Lorch U, Camm AJ (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.

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levofloxacin