{"id":33430,"date":"2018-02-09T11:45:37","date_gmt":"2018-02-09T11:45:37","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=33430"},"modified":"2018-07-21T11:43:38","modified_gmt":"2018-07-21T11:43:38","slug":"us-approve-a-new-low-dose-efavirenz-400-mg-generic-fdc-simfi-lo","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/33430","title":{"rendered":"US approve a lower-dose efavirenz (400 mg) based generic FDC (Simfi Lo)"},"content":{"rendered":"

Simon Collins, HIV i-Base<\/strong><\/p>\n

On 7 February 2018, the US FDA approved a new generic fixed dose combination (FDC) that uses a lower dose of efavirenz (400 mg rather than 600 mg) together with lamivudine and tenofovir DF. [1]<\/strong><\/p>\n

Approval is primarily based on results from the randomised double-blind ENCORE1 study in 630 treatment-naive individuals that reported results three years ago. ENCORE1 reported similar efficacy with slightly fewer side effects in the 400 mg vs 600 mg efavirenz group. [2]<\/p>\n

The most common psychiatric side effects were: abnormal dreams (8.7% vs 11.3%), insomnia (6.2% vs 6.5%), somnolence (3.1% vs 3.9%), depression (3.1% vs 1.6%), nightmare (1.9% vs 2.6%), sleep disorder (2.2% vs 1.3%), and anxiety (1.2% vs 1.3%), in the 400 mg vs 600 mg groups respectively.<\/p>\n

Central nervous system (CNS) symptoms were reported by 40% vs 48% with dizziness (27% vs 35%) and headache (11% vs 11%) in the 400 mg vs 600 mg groups respectively. Different types of rash occurred in 32% vs 26%, with grade 3-4 rash reported in 3% vs 1% (all 600 mg vs 400 mg).<\/p>\n

Approval is for adults and children weighing >35 kg.<\/p>\n

The FDC is manufactured by Mylan and will be marketed with the brand name Simfi Lo.<\/p>\n

For full details see the produced information for the FDC and for the individual drug components. [3]<\/p>\n

comment<\/h3>\n

The option to use this new reduced dose efavirenz-based FDC is welcome \u2013 and reducing the dose of a drug that was still under patent protection is an achievement \u2013 but results from ENCORE1 were first presented almost five years ago. [4]<\/strong><\/p>\n

Although this new formulation might improve quality of life for some people, the reduction in side effects with the 400 mg dose was modest. For this reason, efavirenz is no-longer recommended as a preferred first-line combination in UK guidelines.<\/strong><\/p>\n

Earlier this month Mylan also announced approval in the US and EU of their generic 600 mg efavirenz, that comes with 180 days marketing exclusivity. [5]<\/strong><\/p>\n

The Mylan low dose efavirenz FDC was granted FDA tentative approval (for use outside the US, in association with PEPFAR, <\/strong>even where there is still patent or exclusivity market protection for the product in the US) in March 2017. [6]<\/strong><\/p>\n

References<\/p>\n

    \n
  1. FDA HIV listserv. FDA approves SYMFI LO Tablets (Fixed Dose Combination). (07 February 2018)<\/li>\n
  2. ENCORE1 study group. Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial. Lancet.<\/u> 2014 Apr 26;383(9927):1474-1482. doi: 10.1016\/S0140-6736(13)62187-X. Epub 2014 Feb 10.
    \nhttp:\/\/www.thelancet.com\/journals\/lancet\/article\/PIIS0140-6736(13)62187-X\/fulltext<\/a><\/li>\n
  3. Simfi Lo. Highlights of prescribing information.
    \n    https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2018\/208255s000lbl.pdf <\/a>(PDF)<\/li>\n
  4. Puls R et al. A daily dose of 400mg efavirenz (EFV) is non-inferior to the standard 600mg dose: week 48 data from the ENCORE1 study, a randomised, double-blind, placebo controlled, non-inferiority trial. 7th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 30 June \u2013 3 July 2013, Kuala Lumpur. Oral late breaker abstract WELBB01.
    \n    http:\/\/pag.ias2013.org\/Abstracts.aspx?SID=74&AID=3137<\/a><\/li>\n
  5. Mylan PR. Mylan expands access to HIV\/AIDS medicines with launch of first generic Sustiva tablets. (01 February 2018).
    \n    http:\/\/newsroom.mylan.com\/2018-02-01-Mylan-Expands-Access-to-HIV-AIDS-Medicines-with-Launch-of-First-Generic-Sustiva-R-Tablets<\/a><\/li>\n
  6. US FDA. FDA antiretrovirals approved and tentatively approved in association with the President’s Emergency Plan Expedited Review Process. 193. Tentative approval 10 March 2017.
    \n    https:\/\/www.fda.gov\/InternationalPrograms\/PEPFAR\/ucm119231.htm<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Simon Collins, HIV i-Base On 7 February 2018, the US FDA approved a new generic fixed dose combination (FDC) that uses a lower dose of efavirenz (400 mg rather than 600 mg) together with lamivudine and tenofovir DF. [1] Approval …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-33430","post","type-post","status-publish","format-standard","hentry","category-antiretrovirals"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/33430","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=33430"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/33430\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=33430"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=33430"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=33430"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}