Dosing and drug formulations in children

The dose of antiretroviral drugs given to children is generally based on either weight or body surface area. As children’s bodies are constantly changing, drug doses need to be altered to make sure that a child is not given too much, or too little, of a drug. Health care workers also need to take into account that children under the age of six metabolite drugs faster than adults, so even after adjusting for body weight, they may need to be given higher quantities of ARVs to achieve the same effect that the drugs would have in adults. Information about specific drugs is often limited, and drug manufacturers and expert guidelines use a variety of ways to calculate doses of pediatric ARVs, so there is no uniform dosing system to follow.
Because of the complex nature of pediatric dosing, under- or over-dosing can be a serious risk. Dosing is further complicated by the variety of forms that ARVs may take when provided to children, all of which require different measurements. Infants who are too young to swallow tablets ideally need to be provided with these drugs in the form of syrups or powders, but these formulations are expensive and often impractical. Some syrups need to be refrigerated after opening, which requires a reliable electricity supply, and powders need to be mixed with water, which may be unfeasible in areas where clean drinking water is not regularly available. In addition, the unpleasant taste of syrups and powders can make it difficult for children to take their ARVs every day.
An encouraging development is the relatively recent availability of fixed-dose combination therapies (FDCs), which combine multiple ARVs into a single tablet, for children. Tablets consisting of lamivudine, stavudine and nevirapine have been supplied by the Clinton HIV/AIDS Initiative (CHAI), in conjunction with drug purchase facility, UNITAID, to children in 26 nations. In these countries CHAI’s monthly pediatric treatment formerly consisted of 12 bottles of liquid. For those children who can now access FDCs, only a small container of tablets is needed, making the therapy easier to store, transport and administer.
In areas where there is a lack of affordable pediatric ARV formulations, clinicians often have no choice but to divide adult fixed-dose combination drugs into measures appropriate for children. There is evidence that dividing tablets carries a risk of under- or over-dosing but equally, a significant 2006 study of eight countries concluded that the use of divided adult FDCs can achieve successful and satisfactory results in children. The World Health Organisation supports this practice in situations where no appropriate pediatric medications are available.