Masking the flavour of antiretrovirals in Thai children
Polly Clayden, HIV i-Base
In Thailand, 5,000 children (of 50,000 HIV positive children) are now receiving antiretrovirals (ARVs). The formulations of ARVs produced by the GPO were, until recently, mainly solid dosage forms for adults with only a few liquid dosage forms suitable for children. Children have largely received divided adult formulations.
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),
Thai Red Cross AIDS Research Centre is treating over 150 children with ARVs. Many of these children have taken opened capsule, crushed tablets or large volume of liquids.
Inappropriate formulations and bad taste have been reported to be a barrier to successful paediatric treatment
A paper in AIDS Research and Therapy authored by Torsak Bunupuradah and coworkers reported findings from a study, conducted between September and November 2005, to evaluate whether FLAVORx (a taste masking product for medications) helped 30 Thai children to take opened capsule, crushed tablet and liquid generic ARVs with greater ease.
Before the study ten flavours (strawberry, orange, banana, grapes, bubble gum, water melon, lemon, cherry, vanilla, chocolate) were mixed with Thai GPO generic ARVs, products of Thai GPO and the tastes evaluated by researchers.
The best three flavours for each ARV were then offered to the children first in order to limit the number of flavours children had to taste. Children were followed twice, one month apart. At each visit, the caregivers were asked to complete a questionnaire and interview about the childs adherence, difficulty in taking ARVs, the caregivers technique of giving the medications to the child and their attitude towards using a taste masking product.
For the first ten children for whom caregivers agreed, trough levels of NNRTI or PI were performed at both visits. Samples were taken just prior to the next dose at both visits.
The mean age of the children was 5.2 years (range 1.00- 9.8 years). 40% were boys. All children were receiving generic NRTIs; most combined with generic NVP, branded EFV or Kaletra. The caregivers were 14 mothers, 5 fathers, 6 grandmothers and 5 aunts.
At first visit, the caregivers all reported good adherence among the children but during the interview, most caregivers reported that the child disliked taking ARVs because of the bitter taste particularly generic AZT syrup, 3TC syrup, ddI powder, NVP crushed tablet and EFV opened capsule.
The adherence techniques that the caregivers used varied from using alarm clock, having the child drink fruit juice immediately after the dose, mixing ARV with syrup, honey or food, forcing the child to take ARVs, and bribing the child with treats.
The flavours chosen most frequently by the children at the first visit were strawberry, orange and grape in 23, 15 and 4 children respectively.
At the second visit 24 caregivers reported that, after using FLAVORx, their children had an easier time taking ARV. They all reported that their children liked flavour of FLAVORx and 7/24 children said the medications tasted sweeter.
24/30 (80%) children said that they liked FLAVORx and wanted to continue using it. 15 children (50%) chose to use the same flavor; strawberry (13), orange (2), grape (4), banana (1), and 9 chose to try new flavours; strawberry (6), orange (10).
6 children who did not want to continue using FLAVORx; caregivers of 3 children found it too complicated; 2 children (receiving orange and strawberry flavours) reported burning sensation on the tongue, and 1 child experienced repeated vomiting immediately after taking FLAVORx (strawberry flavour).
Therapeutic drug monitoring (TDM) in the first ten children showed trough levels above the target serum levels at the first and final visits in all except one boy who had undetectable level at the final visit. He was receiving EFV with strawberry and orange flavours. His mother reported excellent adherence and more ease of taking ARV after using FLAVORx. A repeat trough level in this child was 3.74 mg/l; however, he was not taking FLAVORx at that time.
The authors wrote: In eighty percent of children participants, FLAVORx helped them take ARVs with more ease by masking the bitter taste of ARV. Strawberry, orange and grape flavors were the most popular. They found that the masking product did not affect adherence as full adherence was reported in all children despite the problem of bitter tasting ARVs.
They noted that, In the United States, the most popular flavour is bubble gum. This was not selected by any of our patients. Palatable tastes are probably affected by the typical food flavors in each country. This is the first study of FLAVORx in Asian children. It is likely that children from other Asian countries would prefer the same flavours as our children.
They suggest that flavour masking may be explored in other countries especially where adult ARV formulations are used in children.
Bunupuradah T, Wannachai S, Chuamchaitrakool A et al. Use of taste-masking product, FLAVORx, to assist Thai children to ingest generic antiretrovirals. AIDS Research and Therapy, 2006, 3:30.