{"id":13984,"date":"2010-10-01T10:17:15","date_gmt":"2010-10-01T10:17:15","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=13984"},"modified":"2012-07-26T22:26:32","modified_gmt":"2012-07-26T22:26:32","slug":"saquinavir-prolongation-of-qt-interval-roche-issue-dear-doctor-letter","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/13984","title":{"rendered":"Saquinavir prolongation of QT interval: Rocheissue Dear Doctor letter"},"content":{"rendered":"<p>On 5 July 2010 Roche issued the following letter to health care providers. These results followed an FDA mandated phase 4 in HIV-negative volunteers.<\/p>\n<h2>Association of saquinavir (Invirase) with arrhythmogenic risk due to prolongation of the QT and PR intervals<\/h2>\n<p>Dear Healthcare Professional<\/p>\n<p>Roche, in coordination with the European Medicines Agency, would like to notify you of the risk of QT prolongation associated with saquinavir (Invirase), and the subsequent important safety-related addition to the Summary of Product Characteristics (SmPC) for Invirase.<\/p>\n<h3>Summary<\/h3>\n<p>Healthcare professionals should note that:<\/p>\n<ul>\n<li>Saquinavir is contraindicated in patients with congenital or acquired QT prolongation or other predisposing conditions for cardiac arrhythmias, including concurrent therapy with other drugs that prolong the QT and\/or PR interval.<\/li>\n<li>The combination of saquinavir with drugs known to increase the plasma level of saquinavir is not recommended and should be avoided when alternative treatment options are available.<\/li>\n<li>Saquinavir should be discontinued in case of arrhythmias, QT or PR prolongation.<\/li>\n<\/ul>\n<h3>Recommendations<\/h3>\n<ul>\n<li>The recommended dose of saquinavir should not be exceeded since the magnitude of QT and PR prolongation may increase with increased plasma levels of saquinavir.<\/li>\n<li>Baseline and follow-up electrocardiogram recording should be considered (e.g. in patients taking concomitant medication known to increase the plasma level of saquinavir).<\/li>\n<li>Patients should be warned of the arrhythmogenic risk and told to report any signs of cardiac arrhythmias (e.g. chest palpitations, syncope, presyncope) to their physician.<\/li>\n<\/ul>\n<p>For detailed information on the administration and use of saquinavir, please refer to the Summary of Product Characteristics.<\/p>\n<h3>Further information on the safety concern<\/h3>\n<p>Saquinavir is indicated for the treatment of HIV-1 infected adult patients. Saquinavir should only be given in combination with ritonavir and other antiretroviral medicinal products.<\/p>\n<p>The effects of therapeutic (1000\/100 mg twice daily) and supra-therapeutic (1500\/100 mg twice daily) doses of saquinavir\/ritonavir on the QT interval were evaluated in a 4-way crossover, double-blind, placebo- and active-controlled (moxifloxacin 400 mg) study in healthy male and female volunteers:<\/p>\n<p>In the therapeutic and the supra-therapeutic arm 11% and 18% of subjects, respectively, had a QTcS<span>[1]<\/span>* between 450 and 480 msec. In the moxifloxacin active control group, none of the subjects had a QTcS over 450 msec. No study subjects experienced QT prolongation &gt; 500 msec or torsade de pointes in the study.<\/p>\n<p>PR interval prolongation of &gt; 200 msec was observed in 40% and 47% of subjects receiving saquinavir\/ritonavir 1000\/100\u00a0mg twice daily and 1500\/100\u00a0mg twice daily, respectively, and in 3% and 5% of subjects in the moxifloxacin active control group and the placebo arm, respectively.<\/p>\n<p>Events of syncope\/presyncope occurred at a higher than expected rate and were seen more frequently under treatment with saquinavir\/ritonavir.<\/p>\n<h2>Communication information<\/h2>\n<p>The Patient Information Leaflet will be revised in accordance with the updated Summary of Product Characteristics.<\/p>\n<p><a href=\"http:\/\/www.fda.gov\/Drugs\/DrugSafety\/postmarketDrugSafetyInformationforPatientsandProviders\/ucm201221.htm\">Link to FDA announcement<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>On 5 July 2010 Roche issued the following letter to health care providers. These results followed an FDA mandated phase 4 in HIV-negative volunteers. Association of saquinavir (Invirase) with arrhythmogenic risk due to prolongation of the QT and PR intervals &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3],"tags":[],"class_list":["post-13984","post","type-post","status-publish","format-standard","hentry","category-antiretrovirals"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/13984","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=13984"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/13984\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=13984"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=13984"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=13984"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}