Therapeutic drug monitoring (TDM) of atazanavir in pregnancy

Abstract

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

Atazanavir Pharmacokinetics, Efficacy and Safety in Pregnancy: A Systematic Review

“…In total, 23 publications were identified from the PubMed database and, following removal of duplicate citations, 211 from the Ovid platform that included the Embase and Biosis Previews databases. Of these, 13 reports met the criteria for inclusion in this review: 9 examining the pharmacokinetics of ATV/r in pregnant women [15,[29][30][31][32][33][34][35][36], and 4 examining atazanavir exposure [37,38] and neonatal safety [39,40], but without reporting pharmacokinetic data during pregnancy. Of the nine pharmacokinetic studies, four were published in primary literature [15,31,32,34] and five were reported as abstracts and/or posters and/or oral presentations at conferences [29,30,33,35,36].…”

“…Of these, 13 reports met the criteria for inclusion in this review: 9 examining the pharmacokinetics of ATV/r in pregnant women [15,[29][30][31][32][33][34][35][36], and 4 examining atazanavir exposure [37,38] and neonatal safety [39,40], but without reporting pharmacokinetic data during pregnancy. Of the nine pharmacokinetic studies, four were published in primary literature [15,31,32,34] and five were reported as abstracts and/or posters and/or oral presentations at conferences [29,30,33,35,36]. In addition to pharmacokinetic data during pregnancy, several of these studies also included data on efficacy and safety in both maternal and neonatal populations.…”

A Systematic Review of the Use of Atazanavir in Women Infected with HIV-1

“…Pregnancy-related physiological changes, such as increased gastric emptying time, intestinal transit time, gastric pH and blood volume, can affect drug PK profiles. Although systemic exposure to ATV and other ART drugs may decrease during the third trimester of pregnancy [14,89], adequate ATV plasma concentrations were achieved in pregnant women receiving ATV/r 300/100 mg once daily in several studies [84,85,90]. The safety and efficacy of ATV/r in pregnancy is a particularly important issue, as many of the pregnancies that occur in women receiving ART are unplanned, particularly in developing countries [91].…”

Retrospective analysis of the associations and effectiveness of performing therapeutic drug monitoring in pregnant HIV-positive women in two large centres in Manchester

“…Changes in drug plasma concentrations are most marked in the antiretroviral class of protease inhibitors (PIs) where concentrations can drop by 34% in the third trimester, 1–5 especially where Atazanavir (ATV) is taken concomitantly with Tenofovir (TFV). 1 There is, however, little evidence correlating these decreased PI concentrations measured with viral breakthrough (VB), with no demonstrable benefit of increasing third trimester PI doses to address a fall in plasma concentrations.…”

“…1 There is, however, little evidence correlating these decreased PI concentrations measured with viral breakthrough (VB), with no demonstrable benefit of increasing third trimester PI doses to address a fall in plasma concentrations. 1–6 This may in part be due to the decrease of measured levels being offset by an increased proportion of the PI being unbound in the plasma 7 due to the drops in serum albumin and alpha acid glycoprotein concentrations seen in pregnancy. 8,9…”