{"id":7299,"date":"2005-06-15T12:18:25","date_gmt":"2005-06-15T11:18:25","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=7299"},"modified":"2014-05-21T17:43:02","modified_gmt":"2014-05-21T17:43:02","slug":"dosing-nevirapine-in-children","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/7299","title":{"rendered":"Dosing nevirapine in children"},"content":{"rendered":"<p><strong>Polly Clayden, HIV i-Base<\/strong><\/p>\n<p><strong>Dosing antiretrovirals in children is notoriously confusing, utilising different dose calculations, and guidelines are rarely harmonious.<\/strong><\/p>\n<p>In Europe the PENTA guidelines recommend 150mg\/m<sup>2<\/sup> nevirapine BID with a maximum dose of 200mg\/m<sup>2<\/sup> BID. The PACTG has evaluated doses of 120mg\/m<sup>2<\/sup> and 200mg\/m<sup>2<\/sup> BID and the FDA licensed dose is 7mg\/kg BID for children age 2 months to 8 years and 4 mg\/kg BID 8 years and above. Nevirapine is included in international generic products (and in pipeline paediatric generic fixed dose combinations).<\/p>\n<p>Edmund Capparelli from the University of California presented findings from a population pharmacokinetic evaluation of datasets from five PACTG studies to better characterise nevirapine and assess optimum doses [1]. These five studies contained 2449 nevirapine concentrations from 495 infants and children who were aged between one month and 19.5 years (mean 6.6 years).<\/p>\n<p>There were 54% boys and 46% girls in the group evaluated and 40 children were &lt;6 months; 46 children 6 months to 2 years; 152 children 2 to 6 years; 206 children 6 to 12 years and 51 children &gt;12 years old.<\/p>\n<p>Nevirapine concentrations &lt;1000ng\/mL(12%) were excluded from the analysis due to suspected non-adherence.<\/p>\n<p>The population pharmacokinetic analysis was performed using NONMEN (Laplacian) and NLME, both methods had excellent concordance and identified age (a 30% drop from age 5 to 18), ritonavir (a 23% decrease across all age groups) and nelfinavir (a 28% decrease in infants) as covariates associated with lower nevirapine clearance.<\/p>\n<p>The final model predicted an AUC of 63.6 ug.h\/mL for a typical 6.6 year-old (weighing 21.7kg\/0.80m<sup>2<\/sup>) using nevirapine in combination therapy without ritonavir or nelfinavir. The predicted AUC12hr following 150mg\/m<sup>2<\/sup> was 63.9 ng x hr\/mL, which is close to adult exposure receiving 400mg\/day.<\/p>\n<p>Dr Capparelli concluded that a body surface area (BSA) calculation was slightly more consistent than weight based dosing across all age bands. A dose of 150mg\/m<sup>2<\/sup> is less likely to under dose older children than the FDA recommendation based on weight. He added that due to inter patient variability TDM may be useful for children receiving nevirapine.<\/p>\n<p>Reference:<\/p>\n<p>Capparelli E, Blanchard S, Aweeka F et al. Population pharmacokinetics of nevirapine in infants and children\u0097the impact of body size, age, and concomitant therapies. 6th International Workshop on Clinical Pharmacology of HIV Therapy. 28-30 April 2005. Quebec. Abstract 37.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Polly Clayden, HIV i-Base Dosing antiretrovirals in children is notoriously confusing, utilising different dose calculations, and guidelines are rarely harmonious. In Europe the PENTA guidelines recommend 150mg\/m2 nevirapine BID with a maximum dose of 200mg\/m2 BID. The PACTG has evaluated &hellip;<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32],"tags":[142],"class_list":["post-7299","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","tag-pk-workshop-2005"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7299","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=7299"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/7299\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=7299"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=7299"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=7299"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}