" 

  

 This being Wikipedia’s position then I would ask that the following be added to the main quinolone article: 

 Multiskeletal disorders attributed to the fluoroquinolones were first brought to the attention of the FDA in 1972 (Bailey et al)(1) and yet again (by Bailey et al) in 1983 (2). In France, between 1985 and 1992, 100 patients who were being managed with fluoroquinolones had tendon disorders, which included thirty-one ruptures.(3) Worldwide the number of spontaneous tendon ruptures associated with the fluoroquinolone class has grown dramatically and in France alone the numbers had increased from 100 to 921 reported tendon disorders.(4) In a letter published in January 1995, based on similar reports found within the FDA files, including tendon ruptures occurring in the United States and other published articles, the FDA stated that the agency ""will update the labeling [package insert] for all marketed fluoroquinolones to include a warning about the possibility of tendon rupture.""(5) But the FDA failed to do so for more than fourteen years after stating that they would in 1994.   

 As a result of the failure of the FDA to add these warnings, Public Citizen filed a petition with the FDA seeking both the addition of a “Black Box Warning” regarding this risk as well as “Dear Doctor Letters” on August 1, 1996.(6) The FDA responded by issuing a Drug Alert that was printed in an obscure FDA publication but failed to add the “Black Box Warning” or to require “Dear Doctor Letters” be sent.(7) In spite of the overwhelming evidence presented at that 62 Meeting of the Anti-Infective Drugs Advisory Committee (8) (circa 1997) that the fluoroquinolones cause irreversible joint damage (""…If an irreversible cartilaginous lesion can occur, it is very likely that is going to cause problems down the line and we can't even anticipate what they are like…"" (sic)) and the petition filed by Public Citizen in 1996, in 2005 such Black Box Warnings continued to be conspicuously absent.  

 In response to patient’s demands The Office of Attorney General, State of Illinois, filed yet another petition with the FDA (filed May 18, 2005), seeking the same ""Black Box"" warnings and “Dear Doctor Letters” in the same manner as Public Citizen’s 1996 petition.(9) In 2006 Public Citizen renewed its demand of 1996 and filed yet another petition with the FDA.(10) The FDA’s response to these petitions was to state that “FDA has been unable to reach a decision on your petition because it raises complex issues requiring extensive review and analysis by Agency officials.”(11) A decade earlier (1995) the FDA had already stated their intent to add these warnings but never did.(12)  

 Public Citizen filed suit in Federal Court on January 3, 2008 to compel the FDA to respond to their latest petition seeking these upgraded warnings(13)after the FDA ignored Public Citizen's petition for almost 16 months as well as the previous petition filed by the Attorney General of the State of Illinois in 2005.  On July 7, 2008, six months after Public Citizen filed their lawsuit in Federal Court, the FDA notified the makers of fluoroquinolone antimicrobial drugs for systemic use of the need to add a boxed warning to the prescribing information about the increased risk of developing tendinitis and tendon rupture in patients taking fluoroquinolones and to develop a Medication Guide for patients.(14) Kate Resnevic of Public Citizen stated on August 26, 2008 that “The FDA responded to our lawsuit by slapping fluoroquinolones with a black box warning - the strongest warning the FDA can request.”(15) The package inserts for Cipro, Avelox, Proquin XR, Factive, Floxin, Noroxin and Levaquin were changed on September 8, 2008 to reflect these new warnings.(16A, 16B) The new labels did not appear on the FDA site until November 2008.  The generic versions have not been updated to reflect this change as of December 1, 2008. 

 The manufacturers of Cipro, Avelox and Proquin XR, Bayer A. G., issued a Dear Doctor Letter on 10-22-2008,(17)concerning these changes which is available only to licensed physicians via the www.hcnn.net site, which requires that physicians register with the site prior to being allowed access.   The manufacturers of Levaquin, Ortho McNeil, via Janssen Scientific Affairs, LLC also issued a similar letter November of 2008,(18)which is also available via the www.hcnn.net site under these same restrictions.  

 Reference: 

 1.  Nalidixic Acid arthralgia 
 Bailey et al (CMA Journal 1972; 107 601-605) 

 2.  Norfloxacin induced rheumatic disease 
 Bailey et al (NZ Med J 1983; 96; 590) 

 3.  (Royer, R. J.; Pierfitte, C.; and Netter, P.: Features of tendon disorders with fluoroquinolones. Therapie, 49: 75-76, 1994.) 
 http://www.studiomedico.it/allegati/achille.pdf 

 4.  Source: http://www.who-umc.o