{"id":5188,"date":"2009-10-02T21:04:09","date_gmt":"2009-10-02T20:04:09","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=5188"},"modified":"2013-08-16T10:32:12","modified_gmt":"2013-08-16T10:32:12","slug":"raltegravir-trough-levels-reduced-by-etravirine-may-require-use-of-tdm","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/5188","title":{"rendered":"Raltegravir trough levels reduced by etravirine may require use of TDM"},"content":{"rendered":"

www.hiv-druginteractions.org<\/a><\/p>\n

Several pharmoacokinetic studies have reported a negative impact on raltegravir trough concentrations when used in combinations that include etravrine. A letter published in the 27 April 2009 issue of the publication AIDS, from\u00a0Amelie<\/span>\u00a0Menard<\/span> and colleagues, detailed four cases where significant reductions in trough levels of raltegravir were identified in patients who added or included etravirine in their antiretroviral combination.<\/strong> [1]<\/p>\n

These cases suggest that TDM should be used for patients using both drugs together and that the significance of the interaction may be clinically important in some patients.<\/p>\n

The Liverpool HIV drug interaction group [2] summarised these cases:<\/p>\n

\u0093The first case had raltegravir trough concentrations of 189 and 313 ng\/ml on two occasions whilst on darunavir\/ritonavir, enfuvirtide and raltegravir. After switching enfuvirtide for etravirine, raltegravir trough concentrations decreased to 10 ng\/ml and then to 5 ng\/ml one month later. The second case started a combination of tenofovir\/emtricitabine, etravirine and raltegravir. Tenofovir trough concentrations were in the expected range, but raltegravir trough concentrations were considered low (30 ng\/ml). Increasing raltegravir from 800 mg\/day to 1200 mg\/day resulted in an increase in trough concentration (67 ng\/ml). The third case had low raltegravir trough concentrations on two occasions (12 and 9 ng\/ml) whilst receiving darunavir\/ritonavir, etravirine and raltegravir. The final case switched to tenofovir, etravirine and raltegravir. Etravirine trough concentrations were within the normal range, but raltegravir trough concentrations were low (29 ng\/ml).<\/p>\n

In all these cases, raltegravir concentrations were below the mean trough concentration previously observed in initial clinical trials (63 ng\/ml, range 29-118 ng\/ml. [3]<\/p>\n

In two of the cases, concentrations were below the in vitro IC95 for raltegravir of 14.6 ng\/ml.<\/p>\n

An interaction study in healthy volunteers showed that coadministration of raltegravir and etravirine decreased raltegravir trough concentrations by 34%, with minimal effect on AUC and Cmax (~10% decrease). In this study the authors concluded that no dose adjustment for either drug was necessary. [4]<\/p>\n

However, given the wide inter-individual variability in the pharmacokinetics of raltegravir and these reports from HIV-positive subjects, a more cautious approach may be required.<\/p>\n

References:<\/p>\n

    \n
  1. Menard<\/span> A et al. Etravirine-raltegravir, a marked interaction in HIV-1-infected patients:: about four cases. Correspondence, AIDS 27 April 2009, Volume 27 Issue 7, p 869-871. doi:: 10.1097\/QAD.0b013e328329915f
    \nhttp:\/\/www.natap.org\/2009\/HIV\/042009_01.htm<\/a><\/li>\n
  2. News and archive, May 2009.
    \nhttp:\/\/www.hiv-druginteractions.org\/new\/Content.asp?ID=434&TDM=<\/a><\/li>\n
  3. Markowitz M et al. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15.
    \n    http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/17133211<\/a><\/li>\n
  4. Anderson MS et al, Minimal pharmacokinetic interaction between the human immunodeficiency virus nonnucleoside reverse transcriptase inhibitor etravirine and the integrase inhibitor raltegravir in healthy subjects. Antimicrob Agents Chemother. 2008 Dec;52(12):4228-32. Epub 2008 Oct 6.
    \nhttp:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18838586<\/a><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    www.hiv-druginteractions.org Several pharmoacokinetic studies have reported a negative impact on raltegravir trough concentrations when used in combinations that include etravrine. A letter published in the 27 April 2009 issue of the publication AIDS, from\u00a0Amelie\u00a0Menard and colleagues, detailed four cases where …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[],"class_list":["post-5188","post","type-post","status-publish","format-standard","hentry","category-pk-and-drug-interactions"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/5188","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=5188"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/5188\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=5188"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=5188"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=5188"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}