Levofloxacin

from Wikipedia, the free encyclopedia
Structural formula
(S) - (-) - Levofloxacin
General
Non-proprietary name Levofloxacin
other names
  • ( S ) - (-) - 9-fluoro-3-methyl-10- (4-methylpiperazin-1-yl) -7-oxo-2,3-dihydro-7 H -pyrido [1,2,3- de ] [1,4] benzoxacin-6-carboxylic acid ( IUPAC )
Molecular formula C 18 H 20 FN 3 O 4
Brief description

Slightly yellowish powder

External identifiers / databases
CAS number 100986-85-4
EC number 600-146-0
ECHA InfoCard 100.115.581
PubChem 149096
DrugBank DB01137
Wikidata Q424193
Drug information
ATC code
Drug class

Fluoroquinolones - antibiotic

Mechanism of action

Inhibition of the bacteria own enzyme DNA gyrase

properties
Molar mass 361.37 g · mol -1
Physical state

firmly

Melting point

218-220 ° C

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning 08 - Dangerous to health

danger

H and P phrases H: 302-317-334
P: 261-280-342 + 311
Toxicological data

1478 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Levofloxacin is an antibiotic effective drug . Chemically, it is a third generation fluoroquinolone .

Levofloxacin came onto the market in Japan in 1993 and in Germany in 1998, and was approved by the FDA in the USA in 1996 . In 2008 and 2013, the FDA reported on newly observed severe side effects with systemically used fluoroquinolones and ordered appropriate measures. In 2015, according to medical reports, it reassessed the risk-benefit ratio of Cipro-, Levo-, Moxi- and Ofloxacin and significantly restricted its use in 2016. Warnings and restrictions on use of fluoroquinolones have also been issued several times in EU countries. The European Medicines Agency last reassessed the serious, potentially permanent and quality of life-impairing side effects in 2018 and recommended restrictions on use. The Federal Institute for Drugs and Medical Devices then issued a comprehensive notification on April 8, 2019, further restricting the indications for fluoroquinolones and ordering a further update of the instructions for use and specialist information in order to point out possibly irreversible side effects. Doctors were informed via a Rote-Hand-Brief on April 8, 2019 that they would no longer use fluoroquinolones for simple infections.

Chemical information

Levofloxacin is the ( S ) - enantiomer ( L - isomer ) of ofloxacin (a racemate ) and is the pharmacologically active form. Levofloxacin has about twice the effectiveness of ofloxacin in vitro .

The multi-step synthesis of levofloxacin is described in the literature.

Mechanism of action and spectrum of action

Levofloxacin has a bactericidal effect . Like other fluoroquinolones , it inhibits the enzyme gyrase , which is responsible for DNA supercoiling in bacteria during their reproduction cycle. However, an inhibition of DNA replication cannot adequately explain the bactericidal effect of the fluoroquinolones, which is why other mechanisms of action are assumed.

As with all quinolones, the effectiveness against Haemophilus influenzae and Moraxella catarrhalis is very good. Also, pneumococcal and Chlamydia are sensitive to levofloxacin.

application areas

The areas of application are largely the same as those of ofloxacin. Since levofloxacin can be compared to ofloxacin has a higher antibacterial activity, and also higher doses, it is also displayed for the pneumococcal pneumonia .

Fluoroquinolones are recommended not to be used for infections that get better untreated or are not severe . These include infections of the throat, abacterial (chronic) prostatitis , bronchitis , sinusitis , prophylaxis of travelers' diarrhea and recurring infections of the lower urinary tract ( urinary tract infections that do not go beyond the bladder). They should only be used to treat mild or moderate bacterial infections if other antibiotics commonly recommended for these infections cannot be used. It is important that fluoroquinolones should generally be avoided in patients who have previously had serious side effects with a fluoroquinolone or quinolone antibiotic. They should be used with particular caution in the elderly, patients with kidney disease, and patients who have had an organ transplant , as these patients are at higher risk of tendon injury .

Side effects

As with all fluoroquinolones, unwanted effects can occur with levofloxacin . Single, multiple, delayed, and persistent or progressive side effects are possible after taking levofloxacin. Serious side effects with levofloxacin resulted in physical disability in 27% of cases. Compared to other common antibiotics, fluoroquinolones are responsible for most of the permanent disabilities. Deaths and serious side effects are already documented from a single dose. Fluoroquinolone side effects last an average of 14 months to 9 years. A total of 210,705 suspected side effects and 2,991 deaths were reported to the FDA for fluoroquinolones through 2016. For levofloxacin, a total of 98,710 suspected side effects and 1,594 deaths were reported in 24,777 patients. Due to the low reporting rate of 1–10%, the unreported number of fluoroquinolone-associated side effects is estimated at 2–21 million and the unreported number of deaths is estimated at 29,000 to over 299,000.

Musculoskeletal, connective tissue and bone diseases

The risk of tendon damage with levofloxacin is 1: 104. In a group of 65-year-olds and older patients, 2.1% suffered a tendon rupture , 1.1% an aortic aneurysm, and 0.2% a retinal detachment after taking fluoroquinolones . In Germany, a few years after marketing authorization, a significant increase in reports of levofloxacin-induced Achilles tendon ruptures was registered. The drug commission of the German medical profession suggests an increased risk of tendopathy with levofloxacin compared to other fluoroquinolones. This is more likely to affect the elderly and those who take corticoids . However, independent experts found that in many cases these risk factors were not critical. According to FDA reviewers, the risk of tendopathy with fluoroquinolones is almost the same in younger and older patients, with persistent neuromusculoskeletal damage being observed most frequently in the 30 to 59 year old age group (74%). Physical exercise can contribute to an increased risk of tendopathy with fluoroquinolones. This is attributed to an increased need for ATP during muscular exertion, which can increase fluoroquinolone-induced impairments of mitochondrial function and energy supply .

In vitro studies of the effects of fluoroquinolones on human tendon cells show that an inhibition of collagen synthesis and the proliferation of fibroblasts as well as significant mitochondrial damage and cell death occur at concentrations that are reached after only a short application in the blood plasma of quinolone-treated patients. According to pharmacokinetic calculations, levofloxacin can accumulate in the tendon tissue after just two single doses, thereby promoting an increased risk of rupture during exercise. The Achilles tendon is particularly affected by this, as it has to withstand forces that are 12.5 times body weight when running.

According to clinical observations, tendopathies are possible just a few hours after taking the first dose of levofloxacin. Since there can be a month-long latency period between the start of fluoroquinolone therapy and the appearance of the first symptoms, many cases of tendinitis are not recorded and only a few retrospective studies are available on the incidence of fluoroquinolone-induced tendopathies, a high number of unreported cases is assumed.

In connection with levofloxacin-induced Achilles tendon ruptures, there are indications of serious complications, including fall-related hip fractures, deep vein thrombosis, pulmonary embolism, or fatal organ failure. Levofloxacin and structurally analogous fluoroquinolones can also damage other areas of the tendons and muscles. These include the rotator cuff, the biceps and triceps tendons, the epicondyle, hand and finger tendons, hip flexors and gluteal tendons, thigh adductors, the patellar tendon and the plantar fascia. Multiple tendon damage is also possible. This is explained by an increased expression of matrix metalloproteases , which reduce the strength of the tendons . However, since cytotoxic and antiproliferative (growth-inhibiting) effects as well as damage to the mitochondrial DNA have also been observed, a complex pathomechanism can be assumed. Histopathologically, necroses , vascular - ischemic lesions and interstitial edema can be seen .

Fluoroquinolone-induced tendon damage is considered therapy-resistant and often requires surgery, medical rehabilitation , orthopedic aids or the use of a wheelchair. However, these measures cannot prevent long recovery times and consequential functional damage.

Musculoskeletal complications also include myopathies , arthropathies, and impaired fracture healing . Studies on the musculoskeletal toxicity of the fluoroquinolones in juvenile rats suggest that levofloxacin after administration of a single maximum dose fibroblasts and endothelial damage, the permeability of the capillaries is increased and in addition to multiple joint damage and lesions of the tendons, tendon sheaths , synovium and fascia and muscle atrophy triggers on a possible loss of muscle fibers . Serious myalgias as well as myopathies and myasthenias are already possible after a single therapeutic dose and, like arthralgia , can occur frequently. In connection with levofloxacin, cases of persistent myalgia, muscle weakness, muscle atrophy, and muscle spasms and fasciculations have been documented in previously healthy patients; The tongue, throat, larynx and respiratory muscles can also be affected. In patients without predisposing risk factors, potentially life-threatening complications of rhabdomyolysis have been observed even after short-term levofloxacin intake . Crisis deterioration of the neuromuscular disease myasthenia gravis is also possible after a short period of use. The muscle-damaging mechanism of fluoroquinolones is based on an inhibition of neuromuscular transmission and is linked to an intramuscular increase in lactate, disorders of the mitochondrial energy metabolism and increased intracellular calcium concentrations . Inhibition of RYR1 or sarcoplasmic Ca 2+ -ATPase ( SERCA ) by the covalently bound fluorine atom is assumed to be a possible cause of the disturbed calcium homeostasis .

Experimental studies on the arthro- and chondrotoxicity of the fluoroquinolones show osteochondrotic changes and irreversibly progressive joint damage in juvenile rats as well as necrosis in healthy adult human cartilage at subtherapeutic concentrations. Fluoroquinolone-related cartilage and joint damage can be accompanied by insertion tendinopathies or myalgias and manifest themselves in the form of joint swelling, joint effusions , bursitis , synovitis , Baker's cysts , polyarthralgia and acute arthritis or chronic lumbar back pain and frequent crepitation during joint movements. Furthermore, the it can cause arthritic changes in the hip or knee -, shoulder - and ankle come. With long-term use there is a risk of destructive polyarthropathy with osteonecrotic changes, which requires the use of knee and hip prostheses .

Persistent and progressive damage to the skeletal musculature was observed after only a short period of use of levofloxacin and can lead to disabling work incapacity, bed rest and need for care.

Liver and gallbladder diseases

The most common side effects are increased liver enzyme levels as well as nausea and diarrhea.
Acute liver damage occurs at a frequency of 1: 154.

Eye diseases

A study by the Canadian Child and Family Research Institute found that oral administration of fluoroquinolones was associated with a statistically 4.5-fold increased risk of retinal detachment during treatment . The risk disappears immediately after stopping the medication. Similar disorders in the collagen and connective tissue of the vitreous body are suspected to be the pathomechanism, as are the basis for the observed tendon ruptures. Fluoroquinolones can also cause anaphylactic shock , which is attributed to fluoroquinolone-induced mast cell activation.

Vascular disease

The risk of aortic aneurysms and dissections after systemic and inhalation use is increased, especially in older patients, which is why a corresponding warning has been included in the product information.

Indication restrictions due to severe side effects

The Federal Institute for Drugs and Medical Devices has restricted on the recommendation of the Committee for Human Medicinal Products (CHMP) of the European Medicines Agency (EMA), the indication for the antibiotic levofloxacin. The CHMP had classified levofloxacin as a reserve antibiotic in May 2012 . The approved indications are acute bacterial sinusitis , acute exacerbation of chronic bronchitis , community-acquired pneumonia and complicated skin and soft tissue infections. In future, however, their use must be strictly limited to situations in which "other antibiotics that are usually recommended for the initial treatment of the relevant infections are not considered to be indicated".

Statistics of suspicious activity reports

The table lists the suspected adverse reactions most frequently reported for levofloxacin in the EudraVigilance database from 2001 to 2017 . 30,170 individual cases were identified.

Number of reported suspected cases Adverse effect Frequency according to the package insert
2228 Tendinitis / pain Very rare
1571 Tendon tear Not known
927 Dyspnea Occasionally
922 Arthralgia Occasionally
887 Rash Occasionally
772 Pruritus Occasionally
680 Pyrexia Rare
655 nausea Frequently
632 Myalgia Occasionally
632 Pain in one limb Not known
620 pain -
613 Urticaria Occasionally
570 Erythema Occasionally
559 Vomit Frequently
547 diarrhea Frequently

Contraindications

Levofloxacin must not be used in children and adolescents who are growing, during pregnancy and breastfeeding, in patients in patients with epilepsy, and in patients with a history of tendon problems after previous use of fluoroquinolones.

Trade names

  • Tablets, infusion solution: Tavanic (EU, CH), Levaquin (USA, CND), Cravit (J), various generics
  • Eye drops: Oftaquix (D, A)

Web links

Individual evidence

  1. ↑ a b c d e Levofloxacin data sheet from Sigma-Aldrich , accessed on April 7, 2011 ( PDF ).
  2. ^ History of Daiichi - About Us. Daiichi Sankyo , accessed February 25, 2017 .
  3. ↑ Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. FDA
  4. ↑ Center for Drug Evaluation and Research: Drug Safety and Availability - FDA Drug Safety Communication: FDA advises restricting fluoroquinolone antibiotic use for certain uncomplicated infections; warns about disabling side effects that can occur together. Accessed January 31, 2019 .
  5. ↑ a b Quinolone- and fluoroquinolone-containing medicinal products | European Medicines Agency. Retrieved February 2, 2019 .
  6. ↑ BfArM - Risk Assessment Process - Fluoroquinolones: Severe and long-lasting side effects in the muscles, joints and nervous system. Retrieved April 9, 2019 .
  7. ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher, Dieter Reichert: Pharmaceutical Substances. 4th edition, 2 volumes. Thieme-Verlag, Stuttgart 2000, ISBN 978-1-58890-031-9 , pp. 1165-1168; online since 2003 with biannual additions and updates.
  8. ↑ David C. Hooper: Mechanisms of Action of Antimicrobials: Focus on Fluoroquinolones . In: Clinical Infectious Diseases . tape 32 , Supplement_1, March 15, 2001, p. S9-S15 , doi : 10.1086 / 319370 .
  9. ↑ Karl Drlica, Muhammad Malik, Robert J. Kerns, Xilin Zhao: quinolone-Mediated Bacterial Death . In: Antimicrobial Agents and Chemotherapy . tape 52 , no. 2 , February 1, 2008, p. 385-392 , doi : 10.1128 / aac.01617-06 , PMID 17724149 .
  10. ↑ Scientific Institute of the AOK (WIdO): notification. (No longer available online.) Archived from the original on February 3, 2019 ; accessed on February 3, 2019 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.wido.de
  11. ↑ a b c d e Beatrice Alexandra Golomb, Hayley Jean Koslik, Alan J Redd: Fluoroquinolone-induced serious, persistent, multisymptom adverse effects . In: BMJ Case Reports . tape 2015 , October 5, 2015, doi : 10.1136 / bcr-2015-209821 , PMID 26438672 , PMC 4600819 (free full text).
  12. ↑ FDA: FDA / CDER Drug Information Webinar - Fluoroquinolone Safety Labeling Changes. (PDF) In: fda.gov. FDA, April 2017, accessed January 22, 2019 .
  13. ↑ Fatal hypoglycemia with levofloxacin (Tavanic®) (UAW-News - International). July 8, 2006, accessed January 29, 2019 .
  14. ↑ Muge Gulen, Mehmet Oguzhan Ay, Akkan Avci, Ayca Acikalin, Ferhat Icme: Levofloxacin-induced hepatotoxicity and death . In: American Journal of Therapeutics . tape 22 , no. May 3 , 2015, PMID 24067876 .
  15. ↑ Severe cardiac arrhythmias after levofloxacin (TAVANIC). In: arznei telegram. Retrieved January 29, 2019 .
  16. ↑ Saibal Das, Somnath Mondal: Oral Levofloxacin-Induced Optic Neuritis Progressing in Loss of Vision . In: Therapeutic Drug Monitoring . tape 34 , no. 2 , April 1, 2012, p. 124–125 , doi : 10.1097 / FTD.0b013e3182480af4 ( ovid.com [accessed January 29, 2019]).
  17. ↑ Drug Safety and Availability - FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to disabling side effects. Center for Drug Evaluation and Research, accessed January 28, 2019 .
  18. ↑ Kamaljeet Kaur, Raja Fayad, Arpit Saxena, Norma Frizzell, Anindya Chanda: Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: a collaborative investigation by scientists and members of a social network . In: The Journal of Community and Supportive Oncology . tape 14 , no. February 2 , 2016, PMID 26955658 .
  19. ↑ Charles Bennett: Should Black Box Warnings for Fluoroquinolones be Revised: Is the Bar Set Too High? (PDF) Pharmed Out Conference, June 2015, accessed on January 27, 2019 .
  20. ↑ Drugs Commission of the German Medical Association (AkdÄ): Fluoroquinolones: Inflammations and ruptures of the Achilles tendon. (PDF) AkdÄ, accessed on January 27, 2019 .
  21. ↑ Donald A. Redelmeier, Hong Lu, Nick Daneman: fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study . In: BMJ Open . tape 5 , no. 11 , November 1, 2015, p. e010077 , doi : 10.1136 / bmjopen-2015-010077 , PMID 26582407 ( bmj.com [accessed January 27, 2019]).
  22. ↑ Levofloxacin (TAVANIC) - tendon damage is conspicuously common. arznei telegram, accessed on April 11, 2018 .
  23. ↑ a b Torn tendons under levofloxacin. arznei telegram, accessed on April 11, 2018 .
  24. ↑ a b Fluoroquinolones: Inflammation and rupture of the Achilles tendon. (PDF) Medicines Commission of the German Medical Association, accessed on April 7, 2018 .
  25. ↑ Fluoroquinolone Safety Labeling Changes. (PDF) US Food and Drug Administration, April 4, 2017, accessed June 22, 2018 .
  26. ^ A b Mederic Hall, Jonathan T Finnoff, Jay Smith: Musculoskeletal Complications of Fluoroquinolones: Guidelines and Precautions for Usage in the Athletic Population . tape 3 , February 1, 2011 ( researchgate.net [accessed June 22, 2018]).
  27. ↑ Trevor Lewis, Jill Cook: Fluoroquinolones and Tendinopathy: A Guide for Athletes and Sports Clinicians and a Systematic Review of the Literature . In: Journal of Athletic Training . tape 49 , no. 3 , June 2, 2014, p. 422-427 , doi : 10.4085 / 1062-6050-49.2.09 , PMID 24762232 , PMC 4080593 (free full text).
  28. ^ RJ Williams, Erik Attia, TL Wickiewicz, Jo Hannafin: The effect of ciprofloxacin on tendon, paratenon, and capsular fibroblast metabolism . In: The American journal of sports medicine . tape 28 , February 1, 2001, p. 364–9 , doi : 10.1111 / j.1600-0838.2001.110111.x ( researchgate.net [accessed June 22, 2018]).
  29. ↑ Fluoroquinolones cause changes in extracellular matrix, signaling proteins, metalloproteinases and caspase-3 in cultured human tendon cells . In: Toxicology . tape 212 , no. 1 , August 15, 2005, p. 24-36 , doi : 10.1016 / j.tox.2005.04.002 .
  30. ↑ a b Loan Pham, John Christensen: Pharmacokinetic Prediction of Levofloxacin Accumulation in Tissue and Its Association in Tendinopathy . In: Pharmacology and Pharmacy . tape 4 , January 1, 2013, p. 121-131 , doi : 10.4236 / pp.2013.41018 ( researchgate.net [accessed June 22, 2018]).
  31. ↑ a b Yasmin Khaliq, George G. Zhanel: fluoroquinolone-associated tendinopathy: A Critical Review of the Literature . In: Clinical Infectious Diseases . tape 36 , no. 11 , June 1, 2003, p. 1404–1410 , doi : 10.1086 / 375078 ( oup.com [accessed June 22, 2018]).
  32. ↑ Askar, Mona: Influence of ciprofloxacin and various hemofiltrate fractions from patients with chronic kidney disease on tenocytes in humans in vitro . November 19, 2010, doi : 10.25646 / 5266 ( rki.de [accessed June 22, 2018]).
  33. ↑ Levofloxacin . In: Reactions Weekly . tape 1474 , no. 1 , October 1, 2013, p. 27-27 , doi : 10.1007 / s40278-013-6627-4 .
  34. ↑ Levofloxacin-associated bilateral Achilles' tendon rupture, in patient with two secondary hip fractures . In: European Geriatric Medicine . tape 7 , no. 6 , December 1, 2016, p. 581-583 , doi : 10.1016 / j.eurger.2016.03.006 .
  35. ↑ AM Meyers, GA Richards, AD Barrow, F. Bocchiola: Inappropriate use of fluoroquinolone (Levofloxacin / Tavanic) resulting in partial Achilles tendon rupture complicated by deep venous thrombosis . In: Continuing Medical Education . tape 31 , no. 6 , May 29, 2013, p. 229–230 ( cmej.org.za [accessed April 7, 2018]).
  36. ↑ Miguel A. Ramirez, Lars C. Richardson: Pulmonary embolism associated with spontaneous bilateral Achilles tendon rupture . In: The Journal of Foot and Ankle Surgery: Official Publication of the American College of Foot and Ankle Surgeons . tape 46 , no. 4 , July 2007, p. 283-287 , doi : 10.1053 / j.jfas.2007.03.014 , PMID 17586442 .
  37. ^ Andrew W Gottschalk, John W Bachman: Death following bilateral complete Achilles tendon rupture in a patient on fluoroquinolone therapy: a case report . In: Journal of Medical Case Reports . tape 3 , January 6, 2009, p. 1 , doi : 10.1186 / 1752-1947-3-1 , PMID 19126191 , PMC 2631494 (free full text).
  38. ^ LA Sánchez Muñoz, FJ Sanjuán Portugal, J. Naya Machado, J. Castiella Herrero: [Levofloxacin-induced tendon rupture with fatal outcome] . In: Anales De Medicina Interna (Madrid, Spain: 1984) . tape 23 , no. 2 , February 2006, p. 102 , PMID 16680864 .
  39. ↑ Leonie Strobbe, Roger JM Brüggemann, Peter J. Donnelly, Nicole MA Blijlevens: A rare case of supraspinatus tendon rupture . In: Annals of Hematology . tape 91 , no. 1 , January 1, 2012, p. 131-132 , doi : 10.1007 / s00277-011-1220-5 .
  40. ↑ a b Severe shoulder tendinopathy associated with levofloxacin . In: The Brazilian Journal of Infectious Diseases . tape 16 , no. 4 , July 1, 2012, p. 393-395 , doi : 10.1016 / j.bjid.2012.06.015 .
  41. ↑ JM Casparian, M. Luchi, RE Moffat, D. Hinthorn: Quinolones and tendon ruptures . In: Southern Medical Journal . tape 93 , no. 5 , May 2000, pp. 488-491 , PMID 10832946 .
  42. ↑ Chandrakanta Nayak, Barada Prasanna Samal: Quinolone induced tendon rupture: a case series . In: International Surgery Journal . tape 2 , no. 4 , December 14, 2016, p. 725-728 , doi : 10.18203 / 2349-2902.isj20151114 .
  43. ↑ B. Guérin, G. Grateau, G. Quartier, H. Durand: [Rupture of the long biceps tendon following ingestion of fluoroquinolone] . In: Annales De Medecine Interne . tape 147 , no. 1 , 1996, p. 69 , PMID 8763095 .
  44. ↑ Lisa A. Merenda, Laure Rutter, Kimberly Curran, Scott H. Kozin: Rupture Following biceps-to-triceps tendon transfer in Adolescents and Young Adults With Spinal Cord Injury: . In: Topics in Spinal Cord Injury Rehabilitation . tape 18 , no. 3 , 2012, p. 197-204 , doi : 10.1310 / sci1803-197 , PMID 23459326 , PMC 3584780 (free full text).
  45. ↑ Theodore B. Shybut, Ernest R. Puckett: Triceps Ruptures After fluoroquinolone Antibiotics: A Report of 2 Cases . In: Sports Health . tape 9 , 5 Sep / Oct, 2017, pp. 474-476 , doi : 10.1177 / 1941738117713686 , PMID 28610536 , PMC 5582700 (free full text).
  46. Jump up ↑ Jc Le Huec, T Schaeverbeke, D Chauveaux, J Rivel, J Dehais: Epicondylitis after treatment with fluoroquinolone antibiotics . In: The Journal of Bone and Joint Surgery. British volume . 77-B, no. 2 , March 1, 1995, p. 293-295 , doi : 10.1302 / 0301-620X.77B2.7706350 .
  47. ↑ Barbaros Baykal, HL Yamanel, B Cömert: A case of epicondylitis due to ciprofloxacin therapy . In: Turkiye Klinikleri Journal of Medical Sciences . tape 25 , January 1, 2005, p. 316-318 ( researchgate.net [accessed April 7, 2018]).
  48. ↑ Vivian Y Liang, Gena R Ghearing, Saša A Živković: Carpal Tunnel Syndrome After Ciprofloxacin-Induced Tendinitis . In: Journal of Clinical Neuromuscular Disease . tape 11 , no. 3 , March 1, 2010, p. 165-166 , doi : 10.1097 / cnd.0b013e3181d23a9c .
  49. ↑ Jasmine Z. Cheng, Mohit Sodhi, Mahyar Etminan, Bruce C. Carleton: Fluoroquinolone Use and Risk of Carpal Tunnel Syndrome: A Pharmacoepidemiologic Study . In: Clinical Infectious Diseases . tape 65 , no. 4 , August 15, 2017, p. 684-686 , doi : 10.1093 / cid / cix362 .
  50. ↑ Israel Berger, Isak Goodwin, Gregory M. Buncke: Fluoroquinolone-Associated Tendinopathy of the Hand and Wrist: A Systematic Review and Case Report . In: Hand (New York, NY) . tape 12 , no. 5 , September 2017, p. NP121 – NP126 , doi : 10.1177 / 1558944717701237 , PMID 28366020 , PMC 5684946 (free full text).
  51. ↑ Irakli Panchulidze, Reinhold Parth, Patrik Hartl: Spontaneous rupture of the left extensor pollicis longus-, extensor digitorum- and extensor digiti minimi tendons: a case report. In: Hand Surgery . tape 18 , January 1, 2013, p. 89-91 , doi : 10.1142 / S0218810413720027 ( researchgate.net [accessed April 7, 2018]).
  52. ↑ Natalie Smith, Robin Fackrell, Emily Henderson: Ciprofloxacin-associated bilateral iliopsoas tendon rupture: a case report . In: Age and Aging . tape 45 , no. 5 , September 1, 2016, p. 734-735 , doi : 10.1093 / aging / afw092 .
  53. ↑ Anastassios Karistinos, Lonnie E. Paulos: “Ciprofloxacin-induced” bilateral rectus femoris tendon rupture . In: Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine . tape 17 , no. 5 , September 2007, pp. 406-407 , doi : 10.1097 / JSM.0b013e31814c3e69 , PMID 17873557 .
  54. ↑ Kaumakaokalani Shimatsu, Somasundaram Subramaniam, Helen Sim, Paul Aronowitz: Ciprofloxacin-Induced Tendinopathy of the Gluteal Tendons . In: Journal of General Internal Medicine . tape 29 , no. November 11 , 2014, p. 1559–1562 , doi : 10.1007 / s11606-014-2960-4 , PMID 25047394 , PMC 4238198 (free full text).
  55. ↑ Atypical tendopathies with gyrase inhibitors . ( arznei-telegramm.de [accessed April 7, 2018]).
  56. ↑ George Mouzopoulos, Mihalis Stamatakos, George Vasiliadis, Panagiotis Skandalakis: Rupture of adductor longus tendon due to ciprofloxacin . In: Acta Orthopedica Belgica . tape 71 , no. 6 , December 2005, p. 743-745 , PMID 16459870 .
  57. ↑ Bárbara Rosa, Pedro Campos, André Barros, Samir Karmali, Ricardo Gonçalves: Spontaneous bilateral patellar tendon rupture: case report and review of fluoroquinolone ‐ induced tendinopathy . In: Clinical Case Reports . tape 4 , no. 7 , June 3, 2016, p. 678-681 , doi : 10.1002 / ccr3.592 , PMID 27386128 , PMC 4929805 (free full text).
  58. ^ Daniel J. Stinner, Justin D. Orr, Joseph R. Hsu: Fluoroquinolone-associated bilateral patellar tendon rupture: a case report and review of the literature . In: Military Medicine . tape 175 , no. 6 , June 2010, p. 457-459 , PMID 20572481 .
  59. ↑ F. Saint, G. Gueguen, J. Biserte, C. Fontaine, E. Mazeman: [Rupture of the patellar ligament one month after treatment with fluoroquinolone] . In: Revue De Chirurgie Orthopedique Et Reparatrice De L'appareil Moteur . tape 86 , no. 5 , September 2000, pp. 495-497 , PMID 10970974 .
  60. ↑ Jan Beyer, Sebastian Schellong: Bilateral plantar tendinitis during levofloxacin therapy . In: British Journal of Clinical Pharmacology . tape 61 , no. 5 , May 2006, pp. 609 , doi : 10.1111 / j.1365-2125.2006.02631.x , PMID 16669855 , PMC 1885058 (free full text).
  61. ↑ Denis Braun, Nadine Petitpain, Françoise Cosserat, Damien Loeuille, Suleiman Bitar, Pierre Gillet, Philippe Trechot: Rupture of multiple tendons after levofloxacin therapy. In: Joint Bone Spine . Volume 71, number 6, 2004, pp. 586-587, doi : 10.1016 / j.jbspin.2003.10.016 .
  62. ↑ a b Wan-Fai Ng, Michael Naughton: Fluoroquinolone-associated tendinopathy: a case report . In: Journal of Medical Case Reports . tape 1 , no. 1 , July 23, 2007, p. 55 , doi : 10.1186 / 1752-1947-1-55 , PMID 17645801 , PMC 1950514 (free full text).
  63. ↑ Harsha Vyas, Guha Krishnaswamy: Quinolone-Associated Rupture of the Achilles' Tendon . In: New England Journal of Medicine . tape 357 , no. 20 , 2007, p. 2067-2067 , doi : 10.1056 / NEJMicm061227 , PMID 18003963 .
  64. ^ WC McGarvey, D. Singh, SG Trevino: Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: a case report and literature review. Foot Ankle Int. 1998 Aug; 17 (8): 496-498. PMID 8863030 .
  65. ↑ Krzysztof Michalak, Aleksandra Sobolewska-Włodarczyk, Marcin Włodarczyk, Justyna Sobolewska, Piotr Woźniak: Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochemical Implications . In: Oxidative Medicine and Cellular Longevity . tape 2017 , 2017, p. 1–15 , doi : 10.1155 / 2017/8023935 .
  66. ↑ Monique R. Bidell, Thomas P. Lodise: Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk? In: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy . tape 36 , no. 6 , June 2016, p. 679-693 , doi : 10.1002 / phar.1761 .
  67. ↑ More on Fluoroquinolone Antibiotics and Tendon Rupture . In: New England Journal of Medicine . tape 332 , no. 3 , January 19, 1995, p. 193-193 , doi : 10.1056 / nejm199501193320319 .
  68. ↑ Emma Nally, Robert D. Bunning, Luis A. Guerrero: Poster 59 Acute Diffuse Tendinopathy Causing Systemic Weakness and Pain Secondary to Ciprofloxacin Use: A Case Report . In: PM&R . tape 8 , no. 9 , September 2016, p. S180 , doi : 10.1016 / j.pmrj.2016.07.102 ( pmrjournal.org [accessed June 22, 2018]).
  69. ↑ L. Zabraniecki, I. Negrier, P. Vergne, M. Arnaud, C. Bonnet: Fluoroquinolone induced tendinopathy: report of 6 cases . In: The Journal of Rheumatology . tape 23 , no. 3 , March 1996, p. 516-520 , PMID 8832995 .
  70. ↑ JC Le Huec, T. Schaeverbeke, D. Chauveaux, M. Moinard, J. Rivel: [Epicondylitis induced by fluoroquinolones in athletes. Speaking of 2 cases] . In: Journal De Chirurgie . tape 131 , no. 10 , October 1994, p. 408-412 , PMID 7860672 .
  71. ↑ Trevor G Lewis: A rare case of ciprofloxacin-induced bilateral rupture of the Achilles tendon . In: BMJ Case Reports . tape 2009 , March 5, 2009, doi : 10.1136 / bcr.08.2008.0697 , PMID 21686678 , PMC 3028235 (free full text).
  72. ^ Yoko Kashida, Michiyuki Kato: Toxic Effects of Quinolone Antibacterial Agents on the Musculoskeletal System in Juvenile Rats . In: Toxicologic Pathology . tape 25 , no. 6 , November 1997, pp. 635-643 , doi : 10.1177 / 019262339702500615 .
  73. ↑ Silke Heldwein, Edeltraut Garbe, M Zeitz, Thomas Schneider, R Somasundaram: Ciprofloxacin-related acute severe myalgia necessitating emergency care treatment: A case report and review of the literature . tape 47 , April 1, 2009 ( researchgate.net [accessed June 22, 2018]).
  74. ↑ Tsungju O-Lee, Charles E. Stewart, Loren Seery, Christopher A. Church: Fluoroquinolone-induced arthralgia and myalgia in the treatment of sinusitis . In: American Journal of Rhinology . tape 19 , no. 4 , July 2005, p. 395-399 , PMID 16171175 .
  75. ↑ Maria Paparoupa, Sebastian Pietrzak, Adrian Gillissen: Acute Rhabdomyolysis Associated with co-administration of levofloxacin and simvastatin in a patient with normal renal function . In: Case Reports in Medicine . tape 2014 , 2014, pp. 1–4 , doi : 10.1155 / 2014/562929 .
  76. ↑ Hirohisa Nakamae, Masayuki Hino, Takahisa Yamane, Kensuke Ohta, Yasutaka Aoyama: A Case of Rhabdomyolysis due to Levofloxacin . In: Clinical Drug Investigation . tape 20 , no. 3 , September 2000, pp. 203-205 , doi : 10.2165 / 00044011-200020030-00008 .
  77. ↑ Febin John, Ruby Oluronbi, CS Pitchumoni: levofloxacin-induced rhabdomyolysis: a case report . In: Journal of Medical Case Reports . tape 10 , no. 1 , August 24, 2016, p. 235 , doi : 10.1186 / s13256-016-1004-6 , PMID 27557756 , PMC 4997698 (free full text).
  78. ^ S. Christopher Jones, Alfred Sorbello, Robert M. Boucher: Fluoroquinolone-Associated Myasthenia Gravis Exacerbation . In: Drug Safety . tape 34 , no. 10 , October 2011, p. 839-847 , doi : 10.2165 / 11593110-000000000-00000 .
  79. ↑ JP Sieb: Fluoroquinolone antibiotics block neuromuscular transmission . In: Neurology . tape 50 , no. 3 , March 1998, pp. 804-807 , PMID 9521283 .
  80. ↑ a b Thomas Metterlein, Frank Schuster, Martin Hager, Norbert Roewer, Martin Anetseder: Metabolic effects as a cause of myotoxic effects of fluoroquinolones . In: Indian Journal of Pharmacology . tape 47 , no. 6 , November 1, 2015 ( ijp-online.com [accessed June 22, 2018]).
  81. ↑ M. Kato, T. Onodera: Morphological investigation of osteochondrosis induced by ofloxacin in rats . In: Fundamental and Applied Toxicology: Official Journal of the Society of Toxicology . tape 11 , no. 1 , July 1988, p. 120-131 , PMID 3209010 .
  82. ↑ I Cavusoglu, Zeynep Kahveci, S Noyan, Zehra Minbay: quinolones arthropathy induced by ofloxacin in juvenile rats: A light microscopic study . In: Turkish Journal of Medical Sciences . tape 30 , January 1, 2000, pp. 441-447 ( researchgate.net [accessed June 22, 2018]).
  83. ↑ M Menschik, J Neumüller, CW Steiner, L Erlacher, M Köller: Effects of ciprofloxacin and ofloxacin on adult human cartilage in vitro. In: Antimicrobial Agents and Chemotherapy . tape 41 , no. 11 November 1997, pp. 2562-2565 , PMID 9371369 , PMC 164164 (free full text).
  84. ^ Wayne M. Samuelson, Roy A. Pleasants, Martha S. Whitaker: Arthropathy Secondary to Ciprofloxacin in an Adult Cystic Fibrosis Patient . In: Annals of Pharmacotherapy . tape 27 , no. 3 , March 1993, p. 302-303 , doi : 10.1177 / 106002809302700308 .
  85. ↑ H. Chang, MH Chung, JH Kim, JH Kim: Pefloxacin-induced arthropathy in an adolescent with brain abscess . In: Scandinavian Journal of Infectious Diseases . tape 28 , no. 6 , 1996, pp. 641-643 , doi : 10.3109 / 00365549609037977 , PMID 9060073 .
  86. ↑ arthropathy aux fluoroquinolones chez un transplanté hépatique . In: La Revue de Médecine Interne . tape 14 , no. 5 , May 1, 1993, pp. 354-355 , doi : 10.1016 / S0248-8663 (05) 81318-9 .
  87. ↑ M Alfaham, ME Holt, MC Goodchild: arthropathy in a patient with cystic fibrosis taking ciprofloxacin. In: British Medical Journal (Clinical research ed.) . tape 295 , no. 6600 , September 19, 1987, pp. 699 , PMID 3117310 , PMC 1247733 (free full text).
  88. ^ TG Slama: Serum sickness-like illness associated with ciprofloxacin. In: Antimicrobial Agents and Chemotherapy . tape 34 , no. 5 , May 1, 1990, pp. 904-905 , doi : 10.1128 / AAC.34.5.904 , PMID 2360826 .
  89. ↑ Megan Strauchman, Mark W. Morningstar: Fluoroquinolone toxicity symptoms in a patient presenting with low back pain . In: Clinics and Practice . tape 2 , no. 4 , November 28, 2012, doi : 10.4081 / cp.2012.e87 , PMID 24765486 , PMC 3981197 (free full text).
  90. ↑ Atypical tendopathies with gyrase inhibitors . ( arznei-telegramm.de [accessed on June 22, 2018]).
  91. ↑ Xavier Chevalier, Edith Albengres, Marie-Catherine Voisin, Jean-Paul Tillement, Bruno Larget-Piet: A Case of Destructive Polyarthropathy in a 17-Year-Old Youth Following Pefloxacin Treatment . In: Drug Safety . tape 7 , no. 4 , 1992, pp. 310-314 , doi : 10.2165 / 00002018-199207040-00007 .
  92. ↑ Gyrase inhibitors - permanent damage after a short application . ( arznei-telegramm.de [accessed on June 22, 2018]).
  93. ↑ Xiao-Yu Wang, Yuan-Jie Xu, Man Zhu, Wang-Ping Jia, Dai-Hong Guo: Incidence, clinical features, and risk factors of fluoroquinolone-induced acute liver injury: a case-control study. March 8, 2019, accessed March 14, 2019 .
  94. ↑ aerzteblatt.de: Retinal detachment by fluoroquinolone antibiotics , April 4, 2012.
  95. ↑ M. Etminan, F. Forooghian et al. a .: Oral fluoroquinolones and the risk of retinal detachment. In: JAMA: the journal of the American Medical Association. Volume 307, Number 13, April 2012, pp. 1414-1419, doi: 10.1001 / jama.2012.383 . PMID 22474205 .
  96. ↑ Rui Liu, Shiling Hu, Yongjing Zhang, Delu Che, Jiao Cao, Jue Wang, Tingting Zhao, Qianqian Jia, Nan Wang, Tao Zhang: Mast cell-mediated hypersensitivity to fluoroquinolone is MRGPRX2 dependent. In: International Immunopharmacology . Volume 70, number, 2019, pp. 417-427, doi : 10.1016 / j.intimp.2019.02.001 .
  97. ↑ Rote-Hand-Brief on systemic and inhalative fluoroquinolones: Risk of aortic aneurysms and aortic dissections. In: bfarm.de. Federal Institute for Drugs and Medical Devices, October 26, 2018, accessed on October 26, 2018 .
  98. ↑ aerzteblatt.de: Levofloxacin: Indication restrictions due to severe side effects. 4th September 2012.
  99. ↑ Red Hand Letter from Sanofi September 2012. (PDF; 603 kB) Retrieved on September 3, 2012 .
  100. ↑ European database of reported suspected drug side effects. EMA, accessed October 10, 2018 .