{"id":2112,"date":"2015-11-09T01:44:58","date_gmt":"2015-11-09T06:44:58","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2112"},"modified":"2016-03-23T04:39:09","modified_gmt":"2016-03-23T08:39:09","slug":"the-fda-amdac-on-fluoroquinolones-part-2-where-were-the-fq-advocates","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/11\/09\/2112\/the-fda-amdac-on-fluoroquinolones-part-2-where-were-the-fq-advocates\/","title":{"rendered":"The FDA AMDAC on Fluoroquinolones (Part 2): Where Were the FQ Advocates?"},"content":{"rendered":"

\"AMDAC<\/a><\/p>\n

Any FDA meeting is a high-stakes game for industry: \u00a0One never knows how the discussions will go. Some oddball issue may take center stage and usurp much time, creating an unbalanced perspective.\u00a0 At other times, simple issues seem to create controversy, questions are not properly understood in the context of the \u2018regulatory terminology\u2019.<\/p>\n

All company representatives spoke in support of\u00a0current ATS\/IDSA\/AUA\/ERS guidelines even though they are much stricter than existing Product Labels. They pointed out that fluoroquinolones (FQ) were already \u2018held in reserve\u2019, that doctors have experience with this drug class for over 30 years, that labels were regularly updated and that nothing new has come to the fore which would require yet another change.<\/p>\n

Correct, amoxicillin or macrolides are recommended as first line drugs for ABS and ABECB, and nitrofurantoin,TMP\/SMX and fosfomycin for uUTI.\u00a0 Why then, you may ask, are FQ still so often used in these indications?\u00a0 Doctors have become very comfortable, maybe too comfortable, prescribing this powerful class of drugs which are overkill for most of these self-limiting, often viral infections. \u00a0In essence, the guidelines are not followed, and FQ are overprescribed for these 3 indications.<\/p>\n

FDA presented a series of 178 cases extracted from the FAERS system which showed a constellation of side effects with\u00a0disability in its wake, creating the moniker of ‘fluoroquinolone-associated disability’, or FQAD for short.\u00a0 It seems that this new entity is\u00a0not as much a concern to health care providers as to patients.The fact that an unusually high 85% of these reports came directly from patients, not from health care providers, is significant as we are dealing with nothing but\u00a0subjective claims of damage \/ disability. \u00a0There are no objective markers for diagnosis and the syndrome has been self-diagnosed without independent corroboration.<\/p>\n

When 30+ former patients gave their very personal testimony, they had\u00a0a powerful message: \u00a0Don’t use FQ for trivial infections. \u00a0It swayed the committee\u2019s thinking\u00a0just the way it was intended.\u00a0 We heard from panel members how much they were \u2018impressed\u2019 with the stories of \u2018suffering\u2019, and how \u2018inappropriate\u2019 use of FQ in wider populations somehow brings out a higher frequency of adverse events.<\/p>\n

We did not hear from the millions of patients telling the panelists that their lives had been improved or saved by the FQ wonder drugs.\u00a0 I am sure they are out there in huge numbers, but they were not asked to testify\u00a0at the AMDAC and were not heard, leading to a lopsided ruling in favor of the plaintiffs claiming injuries. \u00a0Why didn’t industry bring some of these people\u00a0to the hearings?<\/p>\n

FDA presented data analyses with figures, numbers and percentages, but at the end, it was not a day for \u2018evidence-based medicine\u2019 and balanced\u00a0analysis. Nobody\u00a0asked how often patients taking amoxicillin develop a hypersensitivity reaction, or had Stevens Johnson syndrome after\u00a0TMP\/SMX. \u00a0Do the well-known AEs for these older drugs even make it into the FAERS database?<\/p>\n

Other antibiotics may be\u00a0associated with fewer disability reports but have other severe AEs instead. \u00a0If we restrict the indications for FQ, perhaps we should do so for all antibiotics in use for these indications. \u00a0They all carry serious AE in some patients. \u00a0Some of the side effects of amoxicillin and macrolides can be pretty dramatic (C. difficile infection, QT prolongation). In the case of fosfomycin, we are dealing with a drug much less tested than any FQ.<\/p>\n

At the end we got a skewed vote\u00a0based on testimonials of those who claimed harm from FQ therapy. Industry had a ‘low energy’ defense team at hand and was not prepared for the phalanx of patient advocates presenting their experiences. \u00a0Industry\u00a0could have given us examples of cases that developed complications because of watchful waiting or had poor outcomes with\u00a0amoxicillin or TMP\/SMX. \u00a0We should have heard from families that lost a loved one from meningitis, pneumonia and urosepsis\u00a0because a 2nd line FQ was withheld in line with\u00a0Guideline recommendations.<\/p>\n

As we said above,\u00a0it was not a day for a\u00a0balanced comprehensive analysis.<\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

Any FDA meeting is a high-stakes game for industry: \u00a0One never knows how the discussions will go. Some oddball issue may take center stage and usurp much time, creating an unbalanced perspective.\u00a0 At other times, simple issues seem to create controversy, questions are not properly understood in the context of Continue reading The FDA AMDAC on Fluoroquinolones (Part 2): Where Were the FQ Advocates?<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2115,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[3,18],"tags":[1415,1411,1417,778,1271,1404,1423,725,403,1422,1424,215,220,1429,75,1427,1428,517,42,1420,5,1421,1416,1426,509,898,1425,1583,27,1163,516,213,223,47,1098,723,1412,1106,1405,1419,767,1418,880,1110],"class_list":["post-2112","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-the_news","category-the_viewpoint","tag-abecb-copd","tag-abs","tag-acute-exacerbation-of-chronic-bronchitis","tag-aidac","tag-allphase-pharma-consulting","tag-amdac","tag-american-thoracic-society","tag-amoxicillin","tag-antibiotic-blog","tag-ats","tag-aua","tag-avelox","tag-bayer","tag-c-difficile-colitis","tag-cdi","tag-cfs","tag-chronic-fatigue-syndrome","tag-cipro","tag-ciprofloxacin","tag-faers","tag-fda","tag-fda-adverse-event-reporting-system","tag-fda-advisory-committee-anti-infectives","tag-fluoroquinolone-associated-disability","tag-fluoroquinolones","tag-fosfomycin","tag-fqad","tag-harald-reinhart","tag-idsa","tag-johnson-johnson","tag-levaquin","tag-levofloxacin","tag-macrolide","tag-moxifloxacin","tag-nitrofurantoin","tag-penicillin-allergy","tag-qtc","tag-qtc-prolongation","tag-sinusitis","tag-stevens-johnson-syndrome","tag-tmpsmx","tag-trimethoprim-sulfamethoxazole","tag-urinary-tract-infection","tag-uuti"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-Part-2-slider.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-y4","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":2095,"url":"https:\/\/allphasepharma.com\/dir\/2015\/11\/03\/2095\/amdac-november-5-2015-on-fluoroquinolones-in-as-aecb-uuti-part-1\/","url_meta":{"origin":2112,"position":0},"title":"AMDAC November 5, 2015 on Fluoroquinolones in ABS, ABECB, uUTI\u00a0 – Part 1","author":"Harald","date":"November 3, 2015","format":false,"excerpt":"Only now, a few days before the actual AMDAC meeting, the\u00a0FDA\u2019s Briefing Document becomes available to the public.\u00a0 The topic of the December 5th meeting:\u00a0 Reappraisal of the risk\/benefit of fluoroquinolones (FQ) in approved but \u201cmild, self-limiting\u201d disease indications in light of new post-approval safety issues. 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FDA doing the same, not so much. Profiling based on similarities to other drugs in the same category is nothing new. 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Bad, but not totally unexpected after the AMDAC meeting last November, which taught us a few new things about the drug. It also highlighted how strategic missteps can\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/Solithro-Ketek-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/Solithro-Ketek-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2017\/01\/Solithro-Ketek-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2830,"url":"https:\/\/allphasepharma.com\/dir\/2016\/10\/27\/2830\/solithromycin-solitaire-iv-so-so-results-for-a-so-so-drug\/","url_meta":{"origin":2112,"position":3},"title":"Solithromycin SOLITAIRE-IV: So-So Results for a So-So Drug","author":"Harald","date":"October 27, 2016","format":false,"excerpt":"Just before the November 4th AMDAC on solithromycin, we are being treated to a very fine piece of study write-up. Of course, we are speaking of the File paper on the SOLITAIRE-IV trial, and what a fine piece of crafty penmanship it is, if you haven\u2019t noticed. Just as a\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"soli-iv-newer","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/SOLI-IV-newer.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/SOLI-IV-newer.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/SOLI-IV-newer.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":432,"url":"https:\/\/allphasepharma.com\/dir\/2014\/06\/28\/432\/qt-prolongation-with-azithromycin-and-levofloxacin\/","url_meta":{"origin":2112,"position":4},"title":"QT Prolongation with Azithromycin and Levofloxacin","author":"Harald","date":"June 28, 2014","format":false,"excerpt":"Several antibiotic classes are associated with QTc prolongation: macrolides, quinolones, the antimalarials that share the quinine structure, and many azole antifungals.\u00a0 FDA warned about the proarrhythmic effects of azithromycin in 2013 [i] but it is a recent publication by Rao which brings the message home again with some very disquieting\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"Levofloxacin_ball-and-stick copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/06\/Levofloxacin_ball-and-stick-copy-300x212.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":3323,"url":"https:\/\/allphasepharma.com\/dir\/2017\/04\/25\/3323\/weak-correlation-antibiotic-action-mortality\/","url_meta":{"origin":2112,"position":5},"title":"The Weak Correlation Between Antibiotic Action and Mortality","author":"Harald","date":"April 25, 2017","format":false,"excerpt":"At the recent FDA workshop on narrow-spectrum antibiotic development[1], the concept of using bacteriological response (BR) as an efficacy endpoint was flat-out rejected. 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