{"id":34337,"date":"2018-06-29T08:50:04","date_gmt":"2018-06-29T08:50:04","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=34337"},"modified":"2018-06-29T09:34:10","modified_gmt":"2018-06-29T09:34:10","slug":"janssen-dear-doctor-letter-new-contraindication-against-using-darunavircobicistat-during-pregnancy","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/34337","title":{"rendered":"New contraindication against using darunavir\/cobicistat during pregnancy"},"content":{"rendered":"

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

On 22 June 2018, Janssen issued a Dear Doctor letter (included as next HTB article) against using darunavir\/cobicistat during pregnancy. [1]<\/span><\/b><\/p>\n

This new contraindication is based on significantly reduced plasma levels of darunavir and cobicistat during the second and third trimesters of pregnancy.<\/span><\/p>\n

Darunavir can still be used during pregnancy, but only when boosted by ritonavir<\/span><\/p>\n

The new results are from a pharmacokinetic study presented earlier this year in six HIV positive pregnant women and a more recent FDA update. [2, 3]<\/span><\/p>\n

In summary, the mean exposure (AUC) of darunavir boosted with cobicistat was 56% and 50% lower during the second and third trimesters of pregnancy, respectively, compared with 6 to 12 weeks postpartum. Mean darunavir Cmin concentrations were around 90% lower during the second and third trimesters, compared to postpartum. Exposure of cobicistat was 63% and 49% lower during the second and third trimeters, respectively, as compared to postpartum.<\/p>\n

Although another recent FDA update to the darunavir\/cobicistat in February 2018 cautioned about low darunavir exposure during the third trimester, the new alert goes further in making pregnancy a contraindication. [4]<\/span><\/p>\n

No HIV transmissions to the baby were reported in these studies, but it is unclear whether transmissions have been reported in other settings.<\/span><\/p>\n

The coformulation of darunavir\/cobicisat is marketed as Rezolsta in the EU and Prezcobix in the US.<\/span><\/p>\n

The single pill fixed dose combination of darunavir\/cobicistat\/emtricitabine\/TAF is marketed as Symtuza.<\/span><\/p>\n

References<\/span><\/p>\n

    \n
  1. Janssen Dear Doctor letter. Darunavir\/cobicistat: Increased risk of treatment failure and increased risk of mother-to-child transmission of HIV infection when darunavir and cobicistat co-administered, due to low exposure values during the second and third trimesters of pregnancy. (22 June 2018).
    \nhttps:\/\/i-base.info\/htb\/34341<\/a>
    \n<\/span><\/li>\n
  2. Crauwels HM et al. Pharmacokinetics of total and unbound darunavir in HIV-1\u2013infected pregnant women receiving a darunavir\/cobicistat-based regimen. Poster presented at the 8th International Workshop on HIV & Women, 2-3 March 2018, Boston.<\/li>\n
  3. FDA. Prezcobix pregnancy label update. (05 June 2018).
    \n    https:\/\/www.accessdata.fda.gov\/scripts\/cder\/safetylabelingchanges\/index.cfm?event=searchdetail.page&DrugNameID=94\u00a0\u00a0<\/a><\/li>\n
  4. US darunavir label updated: drug interactions and pregnancy. HTB February 2018.
    \n    https:\/\/i-base.info\/htb\/33410<\/a><\/li>\n<\/ol>\n

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

    Simon Collins, HIV i-Base On 22 June 2018, Janssen issued a Dear Doctor letter (included as next HTB article) against using darunavir\/cobicistat during pregnancy. [1] This new contraindication is based on significantly reduced plasma levels of darunavir and cobicistat during …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[40,3],"tags":[],"class_list":["post-34337","post","type-post","status-publish","format-standard","hentry","category-treatment-alerts","category-antiretrovirals"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34337","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=34337"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/34337\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=34337"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=34337"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=34337"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}