AtriplaR/anti-TB combination in TB/HIV patients. Drug in focus

Co-administration of anti-tuberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and several antiretroviral drugs is complicated by pharmacokinetic drug-drug interaction. Pubmed and Google search following the key words tuberculosis, HIV, emtricitabine, tenofovir efavirenz, interaction were used to find relevant information on each drug of the fixed dose combination AtriplaR RESULTS: Information on generic name, trade name, pharmacokinetic parameter, metabolism and the pharmacokinetic interaction with Anti-TB drugs of emtricitabine, tenofovir, and efavirenz was obtained. Fixed dose combination of emtricitabine/tenofovir/efavirenz (ATRIPLAR) which has been approved by Food and Drug Administration shows promising results as far as safety and efficacy is concerned in TB/HIV co-infection patients, hence can be considered effective and safe antiretroviral drug in TB/HIV management for adult and children above 3 years of age

A Pharmacokinetic and Pharmacogenetic Study of Efavirenz in Children: Dosing Guidelines can Result in Subtherapeutic Concentrations

Background Our main objectives were to study the population pharmacokinetics of efavirenz and to explore the adequacy of dosing guidelines. Methods A total of 33 HIV-1-infected patients were recruited from the Emma Children's Hospital (Amsterdam, the Netherlands). Gender, age, drug formulation, the presence of the c.516G&gt;T polymorphism in the CYP2B6 gene and the quantitation of liver enzymes alanine aminotransferase and aspartate aminotransferase at baseline were collected. A non-linear mixed effect pharmacokinetic model was developed. Results CYP2B6 genotype and drug formulation significantly influenced efavirenz pharmacokinetics. Clearance was 29.7% lower in children carrying the CYP2B6-516-G/T genotype compared with children carrying the G/G genotype. Relative bioavailiability of the oral liquid compared with tablets or capsules was 46.6%. Children carrying the CYP2B6-516-G/G genotype had a 50–70% probability of developing a subtherapeutic trough level of efavirenz and only 1–3% probability of developing a trough level &gt;4 mg/l. To reduce the probability of developing a subtherapeutic trough concentration, we propose to give an adult efavirenz dose to children weighing ≥25 kg and to allometrically scale doses for other weight levels a priori. The dose of the oral solution should be twice the dose of capsules. Conclusions Population pharmacokinetics of efavirenz in children were adequately described. Current dosing guidelines can result in subtherapeutic concentrations in children carrying the CYP2B6-516-G/G genotype and with the liquid formulation. A priori dose adaptations in the paediatric population seem feasible and need prospective validation. </jats:sec