Dosing and drug formulations in children

Dosing and drug formulations in children

The dose of antiretroviral drugs given to children is generally based on either weight or body surface area. Children have traditionally been thought of as being ‘mini adults’ but this is not the case. Children’s bodies are constantly changing and developing and often it is vital that drug doses are altered to ensure that a child is not given too much, or too little, of a drug. The study of how a child’s body reacts to medication is called pharmacokinetics (PK) but current paediatric PK studies mostly focus on 6-18 years old, which misses the early stages of development; a period when the human body changes the most. Pharmacokinetic properties such as absorption, distribution, metabolism and excretion of a drug all influence the efficacy, toxicity and dosing regimen required in a child. As such, information is limited on PK for infants and drug manufacturers and expert guidelines use a variety of ways to calculate doses of paediatric ARVs, so there is no uniform dosing system to follow.²³

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 drugs that are more child friendly such as syrups, powders, sprinkles or ‘melts’ but these formulations are not widely available and are expensive.^{24 25} Unfortunately, a lot of HIV medicine has an unpleasant taste, especially in syrups and powder form. This can make it difficult for children to take their ARVs daily. In addition, it is critical that children’s medicine has clear and concise labelling to ensure that caregivers are able to give an appropriate dosing and ensure adherence.

Since there are still no available, easy-to-use triple drug combinations for children, I do what most doctors are doing: I try to show caregivers such as grandparents how to break adult tablets, hoping that the children will get the doses they need.

Dr Fasineh Samura, Malawi

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 paediatric 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.²⁶

In areas where there is a lack of affordable paediatric 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-dosing²⁷ 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.²⁸ The World Health Organisation supports this practice in situations where no appropriate paediatric medications are available