Limited stability of lopinavir/r (Kaletra) above 25°C

Although Kaletra is generally stored in a refrigerator it retains potency for 2 months at a temperature of 25°C. This limits use for people who do not have access to refrigeration, particularly in hot countries.

Capparelli from University of California, Sand Diego and colleagues performed a small-scale proof of concept study in non-recommended higher temperatures, to evaluate use where refrigeration is not available, particularly in reference to Sub-Saharan Africa.

Kaletra capsules were incubated, individually and in a group of six, in high density polythene bottles, in high humidity, at 35°C and 45°C and contents tested for capsule stability and potency at day 1, 2 and 7 and week 2, 4 and 8.

Physical structure was maintained at 35° for 4 weeks but capsules become distorted by week 8, increasing in weight by 3% and 11% respectively. At 45° degrees the capsules melted together within a week. Potency compared to storage at 4° was >95% at week 4 at both 35°C and 45°C but fell below 85% by week 8.

The study concluded, that dispensing monthly supplies of LPV/r in climates up to 35°C where refrigeration is not available, would maintain potency, and use of this drug in wider settings than is currently available. It did not claim regulatory-standard assessment though, and highlighted the need for formulations that remain more stable at higher temperatures.

Comment

This was an eye opener and a great poster, and clearly there are be storage problems in tropical countries. It would be interesting if future studies also addressed potency.

Equally interesting was the fact that the capsules gained weight – from absorbing water, in humidity. In view of this, there is a need to do bioavailability studies even when the capsules look okay, since alcohol in the caps may be lost and water gained, and this may affect absorption.

Capparelli E et al. Stability of lopinavir/r at elevated temperatures: relevance to HIV therapy in Sub-Saharan Africa. 41st ICAAC, Washington, 2004. Abstract H-868.