Underdosing of antiretrovirals in UK and Irish children with HIV as an example of problems in prescribing medicines to children, 1997-2005: cohort study
- 18 May 2006
- Vol. 332 (7551) , 1183-1187
- https://doi.org/10.1136/bmj.332.7551.1183
Abstract
Objective To measure the extent of underdosing of antiretroviral drugs in children. Design Multicentre cohort study. Setting Clinical centres in hospitals in the United Kingdom and Ireland in the collaborative HIV paediatric study (CHIPS). Participants 615 HIV infected children aged 2-12 years receiving antiretrovirals. Main outcome measures Doses relative to weight and height compared with current recommended doses in 2004 European guidelines. Results The CHIPS cohort of 934 children comprises 80% of diagnosed HIV infected children in the UK and Ireland between January 1997 and March 2005, of which 66% (615) aged 2-12 years were prescribed antiretrovirals. Actual doses standardised to weight or surface area varied widely across individual drugs, antiretroviral class, and calendar time, with children underdosed (prescribed less than 90% of current recommended doses) from 6-62% child time at risk. Three serious issues in prescribing antiretrovirals, which may also be relevant to paediatric prescribing in general, were identified. Firstly, dosing was inadequate before incorrect recommendations at licensing were later revised when important pharmacokinetic results emerged. Secondly, guidelines stating dosage alternatives (by weight/surface area) for the same drug led to different and inconsistent doses. And, thirdly, ongoing growth was not adjusted for. Conclusions Largely inadvertently, HIV infected children in the United Kingdom and Ireland have been underdosed with antiretrovirals, highlighting problems applicable throughout paediatric prescribing.Keywords
This publication has 15 references indexed in Scilit:
- A drug dosage table is a useful tool to facilitate prescriptions of antiretroviral drugs for children in ThailandInternational Journal of STD & AIDS, 2005
- Pharmacokinetics and Pharmacodynamics of Nelfinavir Administered Twice or Thrice Daily to Human Immunodeficiency Virus Type 1-Infected ChildrenClinical Infectious Diseases, 2003
- Pharmacokinetics of nelfinavir and its active metabolite, hydroxy-tert-butylamide, in infants perinatally infected with human immunodeficiency virus type 1The Pediatric Infectious Disease Journal, 2003
- Unlicensed and off label prescription of drugs to children: population based cohort studyBMJ, 2002
- Antiretroviral Pharmacokinetics in the Paediatric PopulationClinical Pharmacokinetics, 2002
- Effect of Combination Therapy Including Protease Inhibitors on Mortality among Children and Adolescents Infected with HIV-1New England Journal of Medicine, 2001
- Current evidence for the use of paediatric antiretroviral therapy – a PENTA analysisEuropean Journal of Pediatrics, 2000
- Reduction in Mortality With Availability of Antiretroviral Therapy for Children With Perinatal HIV-1 InfectionJAMA, 2000
- Combination Therapy with Efavirenz, Nelfinavir, and Nucleoside Reverse-Transcriptase Inhibitors in Children Infected with Human Immunodeficiency Virus Type 1New England Journal of Medicine, 1999
- Treatment of Human Immunodeficiency Virus 1‐Infected Infants and Children with the Protease Inhibitor Nelfinavir MesylateClinical Infectious Diseases, 1999