Best practice in paediatric treatment relies on liquid suspensions, of which a limited range are available, often only in branded versions, at very high prices.
For example, in Uganda, no generic suspensions are available, observes Dr Henry Barigye. A generic tablet of 3TC 150mg costs 270 shillings but 30mls (150mg) of the GlaxoSmithKline suspension costs 10,500 shillings, which is 40 times as much. For combined AZT 300mg/3TC 150mg, the costs are 655 shillings and 18,612 shillings - more than 28 times as much.
Even in India, there is no suspension available for d4T. Yet many babies and young children are anaemic and have problems tolerating AZT.
Professor Norman Nyazema, a pharmacologist who has served as a senior technical advisor to the Medicines Control Agency of Zimbabwe, insists there can be no short cuts. Splitting tablets is unacceptable as a basis for licensing a drug for use in paediatric treatment, and if doctors use a drug beyond its license, the manufacturer cannot be held liable for the consequences. Companies that claim they are meeting public health needs by providing low-cost generic formulations must be pressed to provide a full range, including suspensions for paediatric use.
There is no immediate answer to this dilemma. Liquid formulations suitable for children are clearly needed. Equally, many doctors will continue to split tablets to provide treatment for patients who will otherwise go untreated. What follows is not an endorsement of this practice, but reflects advice received on how to minimise its dangers.
When tablets are split, it is not possible to ensure the two halves are exactly equal in size. On the other hand, this may even itself out over time, especially if the two halves are given as successive doses to the same patient. If a drug is manufactured to international standards (Good Manufacturing Practices - GMP) then the distribution of the drug within tablets should be as even as its distribution between tablets. Whether a tablet is scored or not makes no difference.
The bigger problem is, that half doses (or quarters) may not be the right dose for a particular patient. The correct dosage varies in different ways for different drugs, which makes the splitting of FDCs even more of a problem. Splitting of Triomune (a triple combination) is even less advisable, because it appears to be made by sticking two tablets together.
The correct dosage of d4T and 3TC varies according to the weight of a child.
The formula for d4T = 2mg/kg/day, up to 30kg, split into two equal doses, and then 30mg twice daily for body weight between 30kg and 60kg. Thus, half the 30mg dose, twice daily, might be correct for a child weighing 15kg; and half the 40mg dose, twice daily, might be correct for a child of 20kg.
The formula for 3TC = 8mg/kg/day. Half of the 150mg dose, twice daily, would be correct for a person weighing approximately 20kg. A slight overdose of 3TC is likely to cause fewer problems than an overdose of d4T, but is still not advisable.
The dosage of AZT and nevirapine is varied according to the surface area of the child, which is best calculated using a nomogram based on the child's height and weight. This works by drawing a straight line between the height (on one scale) and the weight (on another scale); this crosses a third scale at a point which gives the surface area in square metres.
An example of such a chart is available online here (countries may have different national reference standards, which should be used for this purpose).
For AZT the daily dose is 360mg/square metre/day (divided into two doses).
For NVP the daily dose is 300-400mg/square metre/day (divided into two doses). The same procedure for lead-in dosing (described earlier in this article) applies to children as well as to adults.
PRABHU: The lack of choice in paediatric formulations is particularly worrying, since with the increasing number of MTCT interventions that are taking place, more paediatric AIDS cases are being diagnosed. Only AZT, 3TC and NVP suspensions are available. Anaemia which is so common in children makes it difficult at times to persist with AZT. d4T is chosen, but with lack of availability of paediatric formulations, adult tablets are split to provide for paediatric doses. This is not good practice, but in the absence of alternatives, we are left with no choice!