{"id":1887,"date":"2015-08-26T16:43:51","date_gmt":"2015-08-26T20:43:51","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=1887"},"modified":"2016-03-18T14:49:06","modified_gmt":"2016-03-18T18:49:06","slug":"avicaz-approval-and-labeling-restrictions","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/08\/26\/1887\/avicaz-approval-and-labeling-restrictions\/","title":{"rendered":"Avycaz Approval and Labeling Restrictions"},"content":{"rendered":"

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

On Feb 25, 2015 the combination of ceftazidime\/avibactam (Avycaz) was approved by FDA for cUTI and cIAI infections in\u00a0patients \u2018who have limited or no alternative treatment options\u2019.\u00a0 As a QIDP drug, Avycaz\u00a0received priority review.\u00a0 Its label states that it is indicated for infections caused by pathogens proven or \u2018suspected to be susceptible\u2019.\u00a0 Post-marketing requirements are for pediatric studies and microbiologic surveillance.\u00a0 We are told that there is some\u00a0concern about efficacy in patients with Clcr < 50 ml\/min.<\/p>\n

The restrictions are in place because \u2018safety and efficacy data for Avycaz is limited, says FDA. As we know enough about ceftazidime, I guess this goes for the avibactam component mainly.

FDA restricts Avycaz to patients\u2018who have limited treatment options\u2019 –<\/span> which is no restriction at all unless you practice in a place where time has stood still and all bugs are of the MDS,\u00a0not MDR variety…\u00a0<\/span><\/p>\n<\/div><\/p>\n

So here is my first question: Which patients are actually excluded? Just about all seriously ill patients have infections with bacteria that are not pan-susceptible and can be considered to have limited treatment options. I thought that\u2019s why we do antibiograms. Hence, the label restriction to patients with\u2018limited treatment\u2019 does not really exclude anyone.<\/p>\n

Second question: Can somebody please explain to me how to recognize a \u2018suspectedly susceptible\u2019 pathogen?\u00a0 When cultures come back showing that an E.coli from a cIAI patient is resistant to a 3rd<\/sup> generation CPN and behaves like an ESBL, I guess it would make sense to consider Avycaz.\u00a0 But it also opens the door for \u2018pre-emptive\u2019 treatment of all patients during the time window when culture and susceptibility results are pending.\u00a0 What prevents the surgical service to make Avycaz the empirical therapy for cIAI when all it takes is suspicion to justify its use ?<\/p>\n

As we have seen, these label restrictions are so soft that they amount to\u2026.very little. \u00a0In all fairness, this wording was put in place by FDA for good reasons.\u00a0 Any harsher restrictions would have achieved little but scare doctors away from using the drug at all.\u00a0 And further create a disincentive for industry to invest in antibiotic development.<\/p>\n

Assume for a moment that the label would restrict Avycaz to patients with \u201cproven infection caused by Avycaz-susceptible ceftazidime-resistant pathogens\u201d?\u00a0 Or to “ESBL producers resistant to any and all 3rd<\/sup> generation cephalosporins”?\u00a0 Clinician would either ignore these restrictions or just use carbapenems even more than now as imipenem, meropenem, ertapenem or doripenem do not have similarly restrictive labeling.<\/p>\n

Hence, I was secretly hoping that Actavis would raise the price tag for Avycaz to stratospheric heights to give pharmacy cost managers the creeps and make\u00a0P&T committees impose restrictions, in line with local resistance patterns and microbiologic surveillance data.<\/p>\n

Well, Actavis did not disappoint us:\u00a0 According to the Medical Letter, the daily WAC\u00a0for Avycaz is $855.\u00a0 By comparison, the costs of a 5-day course of generic cefepime or ceftazidime is only $82 and $60, respectively.\u00a0 When these drugs were still branded, the daily cost was approx. $100. \u00a0In other words, the avibactam component comes at a steep premium\u00a0of more than $750\/day.<\/p>\n

There will be rebates and the like, of course, but with this kind of price differential, market forces will do what no FDA label can do: Control and restrict Avycaz use and prevent it from becoming the \u2018workhorse\u2019 antibiotic on the surgical floors.<\/p>\n

The FDA has shown good judgement in the way it approved Avycaz based on very limited Phase 2 data.\u00a0 After a decade of intransigence this is a good example how FDA can flexibly work with industry.\u00a0 But let\u2019s not go overboard in our praise: the Avycaz approval was a relatively easy decision, given what is already known about the ceftazidime.<\/p>\n

Here some background: An AIDAC (12\/5\/2014) rejected an organism-based indication (for Gram-negative infections with\u00a0limited treatment options) which would have included also\u00a0HABP, VABP and sepsis\/bacteremia.

<\/p>\n

Ceftazidime is
\n<\/strong><\/span>approved for:<\/strong><\/span><\/p>\n