Comparative study of different brands of stavudine capsules for the off-label 'opened capsule' dosing method recommended for HIV-infected infants and children in resource-limited settings

Abstract

AIM: To assess the accuracy of the off-label “opened capsule” dosing method for Stavudine dosing in infants and children. In addition, we assessed the relative ease of dispersion of generic and original capsule preparations in water in order to determine which preparations, if any, are suitable for the off-label “opened capsule” dosing method.
METHOD: We evaluated ten Zerit®, five Generic A, and five Generic B capsules.
Each capsule was dispersed in 30ml water, creating 30 separate solutions. Timed dispersion of each generic was compared to original (Zerit®). Each solution was then centrifuged to remove sediment, and the concentration of active drug (in mg/ml) was analysed using high performance liquid chromatography.
RESULTS: The ease of dispersion of the contents of Generic A capsules was equivalent to that of Zerit®, resulting in a mean recovery of active drug from solution of over 97%, confirming the accuracy of this dosing method. The contents of Generic B capsules were extremely difficult to disperse in water despite prolonged agitation, and the recovery of active drug from solution was reduced as a result.
CONCLUSION: The accuracy of the off-label “opened capsule” dosing method for Stavudine dosing is acceptable. There is no need to instruct caregivers to include sediment in the aliquot given to the infant. However, it is important to avoid supplying generic capsules whose contents do not disperse easily in water, as this may lead to a significant reduction in the amount of active drug that a child receives.