<div id="stripTitle"><font color="#ff1493" size="5">Splitting <i>Triomune</i> tablets for children: smallest get poorest nevirapine dose</font> </div><!-- ICON TOOLBAR --> <div id="toolStrip">&nbsp;</div><!-- END OF ICON TOOLBAR --><!--START OF RECORD STRIP--> <div id="authorDisplay"> <table cellspacing="1" cellpadding="0" width="550" border="0"> <tbody> <tr> <td><strong>Keith Alcorn</strong>, Friday, August 25, 2006</td></tr></tbody></table></div><!--END OF RECORD STRIP--><!-- START OF LEFT COLUMN AREA--> <div id="contentLeft"><!--MAIN TEXT--> <div id="contentBodyText">More evidence that splitting adult antiretroviral tablets for children results in sub-optimal dosing was presented last week at the Sixteenth International Conference in Toronto, with a study from Zambia and Malawi showing that splitting <i>Triomune</i> tablets may lead to serious under-dosing of nevirapine, especially in smaller children under 30kg who received quartered tablets. <br /><br />Difficulties in dosing liquid formulations of antiretrovirals, coupled with their high cost, have led to the widespread practice of splitting adult antiretroviral tablets in order to dose HIV-positive children with a more convenient form of medication. <br /><br />Most commonly, adult tablets of the triple combination tablet <i>Triomune</i> (containing d4T, 3TC and nevirapine) are halved or quartered for children, with the <i>Triomune</i> 30 tablet (which contains 30mg of d4T for patients weighing less than 60kg) used in some cases in order to approximate correct paediatric doses. <br /><br />However, deriving paediatric doses from adult tablets is difficult due to limited information about the correct doses needed at different weights and heights, and by the fact that paediatric dosing is calculated by body surface area rather than by weight or age. A further and poorly understood complication in this population is how malnutrition might affect the pharmacokinetics of antiretroviral drugs. <br /><br />Under-dosing of nevirapine could result in the rapid emergence of resistance to the drug, particularly if the paediatric dose is not updated to reflect changes over time in the child's weight in the youngest children. <br /><br />Researchers from Zambia, Malawi, the United Kingdom’s Medical Research Council and the University of Nijmegen in the Netherlands conducted a large pharmacokinetic study in 127 HIV-positive children aged from eight months to 18 years of age, recruited from two hospitals in Lusaka (Zambia) and Blantyre (Malawi). <br /><br />Children received <i>Triomune</i> tablets that had been halved or quartered for one month before single plasma samples were collected from each child. Malawian samples tended to be taken at a longer interval after dosing (eight hours vs three hours), and the 71 Malawian children were more malnourished. <br /><br />The researchers found that the target nevirapine dose (&gt;300mg/m² was not reached in just over half of the children, with children weighing less than 30kg significantly more likely to have sub-optimal concentrations. <br /><br />The median nevirapine concentration was 6mg/L, but 21% of those receiving quarter or half tablets had concentrations below 3mg/L, a sub-therapeutic drug concentration. <br /><br />Thirty-five per cent of children under the age of three had sub-therapeutic drug concentrations, compared to 25% of 7-10 year-olds and 9% of those aged 11 and over. <br /><br />Wasted children had higher nevirapine concentrations than children of average body weight (body weight was reported as body mass index for age), but stunted children had lower than average nevirapine concentrations, indicating the need for further study of the effects of malnutrition on nevirapine pharmacokinetics in children, said Veronica Mulenga of the University Teaching Hospital in Lusaka, presenting the results. <br /><br />The clinic is now carrying out a paediatric pharmacokinetic study of Cipla’s fixed dose triple combination for children, called <i>Pedimune</i>. This product has been formulated with the aim of providing more accurate doses of d4T, 3TC and nevirapine for children, and will be the first study in children of the bioequivalence of a tablet formulation of a fixed dose antiretroviral product with the liquid formulation. <br /><br /><b>Reference</b> <br /><br />Mulenga V et al. <i>Nevirapine concentrations in HIV-infected children treated with divided fixed dose combination tablets in Malawi and Zambia.</i> Sixteenth International AIDS Conference, Toronto, abstract WeAb0305, 2006. <br /><!--endsubparagraph--></div><!--END OF MAIN TEXT--><br /><br /> <p align="justify">M<em><font color="#0000ff">ot nghien cuu tai Zambia va Malawi cho thay viec chia nho vien Triomune de dieu tri cho tre em co HIV co the dan den thieu nghiem trong lieu Nevirapine dac biet voi cac em duoi 30 kg va chi uong 1/4 vien thuoc. </font></em></p> <p align="justify"><em><font color="#0000ff">Nhung kho khan trong viec xac dinh lieu luong va gia thanh cao cua thuoc ARV dang siro da dan toi tinh trang chia vien thuoc ARV cua nguoi lon cho cac tre em nhiem HIV vi hinh thuc nay co ve giup dinh lieu ARV cho tre em de dang hon. </font></em></p> <p align="justify"><em><font color="#0000ff">Pho bien nhat la vien thuoc ket hop 3 loai thuoc cua nguoi lon la Triomune (co thanh phan la d4T, 3TC va Nevirapine) duoc chia doi hoac chia lam 4 cho tre em. Vien thuoc Triomune 30 co chua 30 mg d4T duoc chi dinh cho cac benh nhan nang duoi 60 kg. </font></em></p> <p align="justify"><em><font color="#0000ff">Tuy nhien dinh luong lieu thuoc cho tre em tu cac vien thuoc cua nguoi lon rat kho vi thieu thong tin ve lieu luong chinh xac theo chieu cao va can nang. Hon nua, lieu dung cho tre em thuong duoc tinh dua vao dien tich be mat co the chu khong phai la can nang va do tuoi. Mot dieu phuc tap nua va cho den nay van chua duoc hieu ro la tinh trang suy dinh duong co the anh huong the nao den tac dong cua thuoc khang virus o tre em. </font></em></p> <p align="justify"><em><font color="#0000ff">Su dung thieu lieu Nevirapine co the dua toi hau qua la nhanh chong khang thuoc, dac biet la khi lieu dung cho tre em khong duoc thay doi theo toc do lon cua tre. </font></em></p> <p align="justify"><em><font color="#0000ff">Cac nha nghien cuu cua Zambia, Malawi, Hoi dong Nghien cuu Y khoa Anh va truong dai hoc Nijmegen (Ha Lan) tien hanh mot nghien cuu lon ve tac dong cua thuoc toi co the cua 127 tre nhiem HIV co do tuoi tu 8 thang toi 18 tuoi tai 2 benh vien o Lusaka (Zambia) va Blantyre (Malawi). </font></em></p> <p align="justify"><em><font color="#0000ff">Sau khi cac chau da uong thuoc vien Triomune chia doi hoac chia lam tu duoc 1 thang, cac nha nghien cuu lay mau mau cua tung chau. Mau mau cua tre tai Malawi duoc lay sau khi uong thuoc 8 tieng, tre tai Zambia duoc lay mau 3 tieng sau khi uong thuoc. 71 tre Malawi tham gia nghien cuu bi suy dinh duong hon nhom tre Zambia. </font></em></p> <p align="justify"><em><font color="#0000ff">Cac nha khoa hoc nhan thay hon mot nua so tre, dac biet la nhung tre can nang duoi 30kg, khong dat duoc dinh muc lieu Nevirapine &gt;300 mg/m^2. </font></em></p> <p align="justify"><em><font color="#0000ff">Nong do Nevirapine trung binh la 6 mg/L nhung 21% tre dung thuoc vien chia doi hoac chia bon co nong do nay duoi 3 mg/L - thap hon nong do can thiet de co tac dung dieu tri. </font></em></p> <p align="justify"><em><font color="#0000ff">35% so tre duoi 3 tuoi, 25% so tre tu 7 -10 tuoi, va 9% so tre tren 11 tuoi khong dat duoc nong do can cho dieu tri.<br /><br />Tre bi suy kiet co nong do nevirapine cao hon tre co can nang binh thuong, nhung tre coi coc thi co nong do nevirapine thap hon. Do vay, cac nha nghien cuu nhan thay can phai nghien cuu them ve tac dong cua tinh trang suy dinh duong doi voi tac dung cua nevirapine cho tre em. </font></em></p> <p align="justify"><br /><em><font color="#0000ff">Mot nghien cuu ve duoc dong hoc cua vien ket hop 3 loai thuoc danh cho tre em do hang Cipla san xuat co ten la Pedimune hien dang duoc tien hanh. Loai thuoc nay duoc hinh thanh voi muc dich cung cap chinh xac hon lieu d4T, 3TC va Nevirapine cho tre em. Day se la nghien cuu dau tien ve su tuong duong sinh hoc cua thuoc ARV dang vien ket hop so voi dang siro cho tre em. </font></em></p><b> <p align="justify"><em><font color="#0000ff">Tham khao</font></em></b><em><font color="#0000ff"> <br /><br />Mulenga V et al. Nevirapine concentrations in HIV-infected children treated with divided fixed dose combination tablets in Malawi and Zambia. Sixteenth International AIDS Conference, Toronto, abstract WeAb0305, 2006. </font></em></p><br class="contentClear" /><br /></div>