{"id":3247,"date":"2006-06-11T07:36:10","date_gmt":"2006-06-11T06:36:10","guid":{"rendered":"http:\/\/moomango.co.uk\/htb\/?p=3247"},"modified":"2013-12-06T17:58:41","modified_gmt":"2013-12-06T17:58:41","slug":"caution-against-dividing-adult-fdcs-triomune-for-young-children","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/3247","title":{"rendered":"Caution against dividing adult FDCs (Triomune) for young children"},"content":{"rendered":"

Polly Clayden, HIV i-Base<\/strong><\/p>\n

While we await paediatric FDCs, several programmes are treating children with divided fixed dose combinations (FDC) Triomune (d4T+3TC+nevirapine) tablets. Although this strategy is important and included in some national guidelines (including Malawi\u0092s), this is not a long-term solution as previous studies have found cut up tablets for young children can result in under dosing of nevirapine.<\/strong><\/p>\n

There are limited PK data on nevirapine in children treated with divided tablets and in whom malnourishment is common.<\/p>\n

In an oral presentation Dr L\u0092homme presented findings from a study to determine the extent of the subtherapeutic concentrations (<3.0 mg\/L) of the nevirapine component and to investigate predictors of nevirapine concentrations in children treated using this strategy.<\/p>\n

This study included 127 HIV positive children aged 3 months – 16 years (median 8.4 years) treated at the Queen Elizabeth Central Hospital, Blantyre, Malawi and the University Teaching Hospital, Lusaka, Zambia who had received divided Triomune at a range of doses (see table one) for at least a month.<\/p>\n

Steady-state plasma nevirapine concentrations were determined in the children. Centre-stratified regression with backwards elimination (p<0.1) was used to identify predictors from height-for-age, BMI-for-age, age, sex, post-dose sampling time and dose\/m2<\/sup>\/day.<\/p>\n

The 71 Malawian children were similar ages (median 8.4 years), but more malnourished (BMI-for-age -0.89, height-for-age -3.15) and had longer post-dose sampling times (8.9 hours) than the 56 Zambian children (8.5 years, -0.50, -1.84, 3.5 hours respectively).<\/p>\n

Table 1: Triomune tablets and daily nevirapine dose<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
Number of Triomune tablets<\/th>\nTotal daily dose (mg)<\/th>\nNumber of children (n=127)<\/th>\n<\/tr>\n
\u00bc once daily<\/td>\n50<\/td>\n6<\/td>\n<\/tr>\n
\u00bc twice daily<\/td>\n100<\/td>\n9<\/td>\n<\/tr>\n
\u00bc once daily, \u00bd once daily<\/td>\n150<\/td>\n18<\/td>\n<\/tr>\n
\u00bd twice daily<\/td>\n200<\/td>\n52<\/td>\n<\/tr>\n
\u00bd once daily, \u00be once daily<\/td>\n250<\/td>\n12<\/td>\n<\/tr>\n
\u00be twice daily<\/td>\n300<\/td>\n2<\/td>\n<\/tr>\n
\u00be once daily, whole once daily<\/td>\n350<\/td>\n2<\/td>\n<\/tr>\n
whole twice daily<\/td>\n400<\/td>\n23<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Overall, the median nevirapine concentration was 6.0mg\/l (IQR 3.8-8.2mg\/L) percentage of children receiving sub-therapeutic doses of nevirapine (<3.00mg\/L) in this analysis was 18% (see table 2).<\/p>\n

Table 2: Percentage of patients with subtherapeutic nevirapine (<3.0mg\/L)<\/strong><\/p>\n

    \n
  • Overall: 18%<\/li>\n
  • >300mg\/m2<\/sup>\/day: 3%<\/li>\n
  • 240-300: 20%<\/li>\n
  • <240: 25%<\/li>\n<\/ul>\n

    The median nevirapine levels were 4.8mg\/L [IQR: 2.8, 6.5; range: 0.15,15.4] and 7.0 mg\/L [IQR: 5.4,10.5; range 0.15,17.1] in Malawian and Zambian children respectively. Only the children receiving the nearly adult dose (350-400mg nevirapine\/day) received the target dose of 300 mg\/m2\/day (median 337 mg\/m2 [IQR 303-366; range 274-454], with only 2% of these children with <3 mg\/L (considered subtherapeutic).<\/p>\n

    Those prescribed 50-200 mg\/day (quarter\/half tablets) were more frequently underdosed (median 236 mg\/m2 [IQR 217,267; range 120- 354], with 21% <3mg\/L); as were those prescribed >200-<350mg (median 263 mg\/m2 [IQR 260,271; range 245-292], with 21% children <3mg\/L.<\/p>\n

    The investigators found lower height-for-age (indicating stunting) (+0.37 mg\/L per unit higher [95% CI – 0.013, +0.75], p=0.06), lower prescribed dose\/m2 (+0.67 mg\/L per 50mg\/m2 higher [+0.014, +1.32], p=0.05) and younger age (+0.15 mg\/L per year older [-0.022, +0.31], p=0.09) were independently associated with lower nevirapine levels.<\/p>\n

    They reported no significant independent effect of lower BMI-for-age (indicating wasting) (-0.33mg\/L per unit higher [-0.76, +0.09], p=0.12), although this was a stronger predictor for the Malawian children (-0.51 [-1.01, -0.02], p=0.04).<\/p>\n

    The investigators concluded that dividing Triomune could put children at risk for nevirapine underdosing. They wrote: \u0093To avoid nevirapine underdosing in young children, divided FDC Triomune should be used with caution; the use of quarter tablets is not recommended. Nevirapine levels may be reduced in stunted but increased in wasted children. Further studies investigating these relationships are required.\u0094<\/p>\n

    Reference:<\/p>\n

    L\u0092homme R, Ellis R,J, Ewings F et al. Nevirapine concentrations in HIV-infected children treated with divided fixed dose combination tablets in Malawi and Zambia. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon. Abstract 2.<\/p>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base While we await paediatric FDCs, several programmes are treating children with divided fixed dose combinations (FDC) Triomune (d4T+3TC+nevirapine) tablets. Although this strategy is important and included in some national guidelines (including Malawi\u0092s), this is not a …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32],"tags":[143],"class_list":["post-3247","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","tag-pk-workshop-2006"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/3247","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=3247"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/3247\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=3247"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=3247"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=3247"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}