{"id":2095,"date":"2015-11-03T02:10:31","date_gmt":"2015-11-03T07:10:31","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2095"},"modified":"2016-03-23T04:39:09","modified_gmt":"2016-03-23T08:39:09","slug":"amdac-november-5-2015-on-fluoroquinolones-in-as-aecb-uuti-part-1","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/11\/03\/2095\/amdac-november-5-2015-on-fluoroquinolones-in-as-aecb-uuti-part-1\/","title":{"rendered":"AMDAC November 5, 2015 on Fluoroquinolones in ABS, ABECB, uUTI\u00a0 &#8211; Part 1"},"content":{"rendered":"<p><a href=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-slider.jpg?ssl=1\"><img data-recalc-dims=\"1\" loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-2102 aligncenter\" src=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-slider.jpg?resize=530%2C149&#038;ssl=1\" alt=\"AMDAC - slider\" width=\"530\" height=\"149\" srcset=\"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-slider.jpg?w=640&amp;ssl=1 640w, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-slider.jpg?resize=300%2C84&amp;ssl=1 300w\" sizes=\"auto, (max-width: 530px) 100vw, 530px\" \/><\/a><\/p>\n<p>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 5<sup>th<\/sup> 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.<\/p>\n<p>The document is 617 pages long and provides a thorough review of study data of FQ in the indications challenged: ABS, ABECB-COPD, and uUTI.\u00a0 None of the safety concerns are new; all have found their way into the labels of Cipro, Avelox, Levaquin, and Factive by now.\u00a0 They are: tendonitis, neuropathy, and QTc prolongation.<\/p>\n<p>After providing an excellent, thorough review of the efficacy and safety data of FQ, FDA asks a simple question:\u00a0 Is the use of these drugs justified in light of the mild nature of these diseases?\u00a0 Or should these indications be struck from labels?<\/p>\n<p>The answer is easy: It\u2019s a judgement call.\u00a0 A toss-up with good arguments pro and con.\u00a0 There is no right or wrong answer and certainly different Health Authorities, looking at the same data, would easily come to different conclusions.\u00a0 And yes, it\u2019s also a political ploy by an FDA that would like to get external answers for questions and justification for actions that they cannot get a grip on internally for quite some time.<\/p>\n<p>Of course the FDA is right:\u00a0 These drugs are being overused in these indications.\u00a0 But \u2013 I would argue &#8211; not because of bad intentions by doctors, or as a result of the marketing muscle of Big Pharma.\u00a0 They are overused because of our state of collective ignorance.<\/p>\n<p>Nobody can argue with the FDA\u2019s razor-sharp logic that antibiotics should be reserved for those that need them. The only problem: We just don\u2019t know when to use them correctly each time. \u00a0Diagnostics are just not in place that would help even with seemingly basic determinations of antibiotic need.<\/p>\n<p>First FDA tenet:\u00a0 Antibiotics should only be used if and when bacteria are involved in the disease process.<\/p>\n<ul>\n<li>Sinusitis etc: As of Nov. 2015, we still cannot properly distinguish between viral and bacterial sinusitis. \u00a0The same is true for otitis media and CAP (see Dr. Bartlett\u2019s recent comments).\u00a0 For all the respiratory infections, there is just no diagnostic or imaging tool that distinguishes bacterial from all other possible etiologies not amenable to antibiotics which make up the list of differential diagnoses.<br \/>\nEven if we had the diagnostics to positively identify bacterial disease, the FDA may still think that trivial diseases should be left untreated.\u00a0 Here I beg to differ: it is not up to the FDA to tell doctors which bacterial infections in private practice warrant antibiotic therapy.<\/li>\n<\/ul>\n<p>Second FDA tenet:\u00a0 Antibiotics should not be used in self-limiting mild diseases because the benefits don\u2019t outweigh the risks:<\/p>\n<ul>\n<li>ABS, ABECB-COPD, uUTI: It is correct that prior to the advent of antibiotics, patients survived these diseases in most cases. This does not make them trivial: the potential for a mild form of sinusitis to turn severe, for an otitis media to result in hearing loss or mastoiditis, and for a walking pneumonia to become a walk to the graveyard is real.\u00a0\u00a0 How about the development of septic complications?<br \/>\nGoing a step further: Does FDA believe prophylaxis has a place for certain situations or is it always tantamount to treating colonization?<\/li>\n<\/ul>\n<p>Third FDA tenet: Antibiotics should not be approved \/ used when a benefit cannot be proven in a well-controlled, unbiased clinical trial setting:<\/p>\n<ul>\n<li>ABS, ABECB-COPD, uUTI: All FQ were approved for these indications following the Guidelines in existence at the time.\u00a0 More recently, FDA has pushed hard to obtain objective data demonstrating efficacy over placebo, instead of relying on non-inferiority studies and worrying about biocreep.<br \/>\nThis information has now become available for sinusitis in which\u00a0placebo studies have helped define which patients are likely to benefit (e.g., Lindbaeck). \u00a0For uUTI, FDA acknowledges that such data exist as well.<\/li>\n<\/ul>\n<p>FDA is to be commended for their critical reappraisal of approved indications in light of new data.\u00a0 There is not much work these days at the agency with the review of new NDAs for anti-infectives, so we are treated to this retrospective re-evaluation of the therapeutic index. As we all know, time is not kind to antibiotics:\u00a0 they lose efficacy over time, and their safety profile statistics can only get worse over time.\u00a0 Of course, the benefit\/risk ratio will seemingly become\u00a0worse over time.<\/p>\n<p>But there are other trends as well which should not be neglected.\u00a0 The increasing resistance of uropathogens to FQ \u00a0has already led to a change in the Practice Guideline for uUTI\u00a0(a main area of use for ciprofloxacin). Nitrofurantoin and fosfomycin are now first-line agents for uUTI.\u00a0 The medical experts have downgraded FQ already, and we can expect a dramatic shift in antibiotic use patterns for this indication.<\/p>\n<p>What does the FDA action mean for industry, esp. for Bayer and Johnson, the main players in this arena?\u00a0 A big yawn there, not much is at stake for them.\u00a0 The recognition that antibiotics are \u2018undervalued\u2019 will drive up prices for the few we still have, including the FQ class.\u00a0 Remember, the pipeline is pretty empty.<\/p>\n<p>If AMDAC recommends removal of the indications for uUTI, ABS and ABECB-COPD and if FDA follows this advice, commercial losses will be minor.\u00a0 Companies can always \u2018adjust\u2019 the price to compensate.\u00a0 Internally, Big Pharma managers will feel justified in their decision to leave the field and move to more lucrative markets.\u00a0 Without a competitor in sight, Bayer and J&amp;J stand to lose nothing.<\/p>\n<p>The US is not living in \u2018splendid isolation\u2019.\u00a0 Not even Donald Trump can build a wall defending us from bad bugs entering the US without an FDA visa.\u00a0 Hence, any FDA action \u2013 like so many other antibiotic stewardship actions &#8211; will have little overall economic impact. \u00a0However, in the quest to \u2018protect the public\u2019, individual patients will suffer.<\/p>\n<p>Stay tuned for Part 2\u2026<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>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. The document is 617 <a class=\"more-link\" href=\"https:\/\/allphasepharma.com\/dir\/2015\/11\/03\/2095\/amdac-november-5-2015-on-fluoroquinolones-in-as-aecb-uuti-part-1\/\">Continue reading <span class=\"screen-reader-text\">  AMDAC November 5, 2015 on Fluoroquinolones in ABS, ABECB, uUTI\u00a0 &#8211; Part 1<\/span><span class=\"meta-nav\">&rarr;<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2102,"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":[1410,1415,1411,360,778,1271,1404,403,215,220,1407,517,42,1408,798,5,224,898,799,1583,1163,516,213,1409,47,1098,916,1406,1413,77,1412,262,1405,1414,880,1110],"class_list":["post-2095","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-the_news","category-the_viewpoint","tag-abecb","tag-abecb-copd","tag-abs","tag-adverse-events","tag-aidac","tag-allphase-pharma-consulting","tag-amdac","tag-antibiotic-blog","tag-avelox","tag-bayer","tag-bronchitis","tag-cipro","tag-ciprofloxacin","tag-copd","tag-factive","tag-fda","tag-fluoroquinolone","tag-fosfomycin","tag-gemifloxacin","tag-harald-reinhart","tag-johnson-johnson","tag-levaquin","tag-levofloxacin","tag-mastoiditis","tag-moxifloxacin","tag-nitrofurantoin","tag-ofloxacin","tag-otitis-media","tag-peripheral-neuropathy","tag-pneumonia","tag-qtc","tag-sepsis","tag-sinusitis","tag-tendonitis","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-slider.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-xN","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":2112,"url":"https:\/\/allphasepharma.com\/dir\/2015\/11\/09\/2112\/the-fda-amdac-on-fluoroquinolones-part-2-where-were-the-fq-advocates\/","url_meta":{"origin":2095,"position":0},"title":"The FDA AMDAC on Fluoroquinolones (Part 2): Where Were the FQ Advocates?","author":"Harald","date":"November 9, 2015","format":false,"excerpt":"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\u2026","rel":"","context":"In &quot;The News&quot;","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"AMDAC Part 2 - slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-Part-2-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-Part-2-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/AMDAC-Part-2-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2998,"url":"https:\/\/allphasepharma.com\/dir\/2017\/01\/12\/2998\/omissions-commissions-errors-blunders-solithromycin\/","url_meta":{"origin":2095,"position":1},"title":"Omissions \u2013 Commissions \u2013 Errors \u2013 Blunders &#8211; Solithromycin","author":"Harald","date":"January 12, 2017","format":false,"excerpt":"Cempra received a complete response letter (CRL) as a X-mas present from FDA, and the news was pretty bad for company investors. 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 &quot;QIDP Antibiotics&quot;","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":2129,"url":"https:\/\/allphasepharma.com\/dir\/2015\/11\/14\/2129\/ibuprofen-for-uuti-interesting-pilot-trial-but-more-to-come-soon\/","url_meta":{"origin":2095,"position":2},"title":"Ibuprofen For uUTI: Interesting Pilot Trial But More to Come Soon","author":"Harald","date":"November 14, 2015","format":false,"excerpt":"At the recent AMDAC, the frequent mention of an unusual uUTI study caught my attention.\u00a0 In their review of placebo-controlled trials, FDA mentioned a study comparing ciprofloxacin with Ibuprofen (Motrin), an NSAID drug without any antibacterial activity[1].\u00a0 By the outcome of total symptom relief, there was no difference. Obviously, there\u2026","rel":"","context":"In &quot;Recent Literature&quot;","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"uUTI study slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/uUTI-study-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/uUTI-study-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/11\/uUTI-study-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":2862,"url":"https:\/\/allphasepharma.com\/dir\/2016\/11\/07\/2862\/profiling-solithromycin-fda-amdac-on-solithera\/","url_meta":{"origin":2095,"position":3},"title":"Profiling Solithromycin: FDA AMDAC on Solithera","author":"Harald","date":"November 7, 2016","format":false,"excerpt":"Police profiling based on race, sex or gender is a highly controversial practice. FDA doing the same, not so much. Profiling based on similarities to other drugs in the same category is nothing new. Class labeling can be expected for the next new B-lactam or quinolone regardless of whether during\u2026","rel":"","context":"In &quot;QIDP Antibiotics&quot;","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"solithro-pipe-magritte","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/11\/Solithro-Pipe-Magritte.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/11\/Solithro-Pipe-Magritte.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/11\/Solithro-Pipe-Magritte.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":1907,"url":"https:\/\/allphasepharma.com\/dir\/2015\/09\/03\/1907\/mrsa-fluoroquinolones-an-interesting-bunch-playing-a-high-stakes-game\/","url_meta":{"origin":2095,"position":4},"title":"MRSA Fluoroquinolones \u2013 An Interesting Bunch Playing a High-Stakes Game","author":"Harald","date":"September 3, 2015","format":false,"excerpt":"Fluoroquinolones (FQ) of the ofloxacin\/ciprofloxacin generation were mainly active against Gram-negative bacteria, distinguishing themselves as cidal IV\/PO drugs with high\u00a0potency\u00a0against most lactose- and non-lactose fermenters.\u00a0 They were excellent against problem pathogens like P. aeruginosa, had excellent efficacy\u00a0against Salmonellae, the Gonococcus and other Neisseriae, and you could count on them for\u2026","rel":"","context":"In &quot;The News&quot;","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"antiMRSA 1 copy","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/antiMRSA-1-copy.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/antiMRSA-1-copy.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/09\/antiMRSA-1-copy.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":2095,"position":5},"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 &quot;QIDP Antibiotics&quot;","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":[]}],"jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2095","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/comments?post=2095"}],"version-history":[{"count":11,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2095\/revisions"}],"predecessor-version":[{"id":2111,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/posts\/2095\/revisions\/2111"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media\/2102"}],"wp:attachment":[{"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/media?parent=2095"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/categories?post=2095"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/allphasepharma.com\/dir\/wp-json\/wp\/v2\/tags?post=2095"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}