Children with HIV underdosed with antiretrovirals
Ian Boddy/Science Photo Library
Children’s doses need to achieve a balance between safety
and efficacy |
Problems in prescribing drugs for children were highlighted by research published in the BMJ last week (2006;332:1183) which shows that children with HIV in the UK and Ireland have been underdosed with antiretrovirals for the past nine years.
The UK and Irish collaborative HIV paediatric study (CHIPS) looked at
data from 934 children diagnosed with HIV between 1997 and 2005, 615
of whom were prescribed antiretrovirals. The researchers compared the
total daily dose of antiretrovirals with the current recommended daily
dose during three periods: 1997–99, the first period in which effective
treatment became available for children; 2000–02, after results
of paediatric pharmacokinetic studies and European guidelines were published;
and 2003–05. The researchers found that the proportion of time
that drugs were prescribed at less than 90 per cent of the current recommended
dose varied between 6 per cent and 62 per cent.
“Some antiretrovirals were dosed suboptimally because of inadequate
pharmacokinetic data at licensing, other underdosing seems attributable
to confusing
and inconsistent dosage strategies or to failure to respond to growth,
especially at the extremes of weight bands,” say the researchers.
Limitations in formulation and the slow uptake of new dosing information
that emerged after licensing also contributed to underdosing.
The researchers believe that expert guidelines stating alternative dosage
strategies (by weight or surface area) for the same drug lead to inconsistent
dosing and undermine the quality of paediatric prescribing. They say
that these issues apply to prescribing for children in general, particularly
for other chronic diseases that need long-term medication.
Dinesh Mehta, executive editor of the British National Formulary, commented: “We
agree that doses for children need to be calculated with care and that
a rational basis should be applied. However, a one-size-fits-all approach
might not be appropriate for calculating doses across the whole spectrum
of paediatrics.
“Ultimately doses should be about achieving the best balance between
safety and efficacy, but secondary considerations such as convenience,
compliance
and available formulations also play a part. A further consideration
is established practice — if particular dosage regimens have been
shown to work and have become established, it is not appropriate to change
these just to conform to a new (and possibly untested) paradigm for doses.
“For many drugs, with wide safety margins, it is convenient (and
safe) to base doses on the age of the child; in such cases the prescriber
will
be able to make allowances for the child whose size is significantly
outside the norm.” |
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