ICAAC: Kaletra: stability and potency decline rapidly in hot climates

Lopinavir / ritonavir (Kaletra) capsules are likely to deteriorate rapidly in resource-limited settings with hot climates and need to be stored and dispensed with care, say researchers from the United States National Institutes of Health.

Kaletra is recommended as a second-line treatment option in resource-limited settings in World Health Organization treatment guidelines, and is also being investigated in a number of clinical trials as first line therapy, both for mothers exposed to nevirapine perinatally and for general use.

Kaletra’s manufacturer Abbott Laboratories has shown that capsules are stable and potent for two months when stored at 25ºC. However, temperatures in African pharmacies and homes may exceed 40ºC for long periods, so the researchers were keen to find out what would happen to Kaletra capsules in such conditions.

They simulated a hot and humid climate in the laboratory, and tested six capsules at temperatures of 35 and 45ºC. Each capsule was visually inspected, weighed and assayed for lopinavir and ritonavir content at days 1, 2, 7, 14, 30 and 60, and results were compared with capsules stored at 4ºC.

Within one day of entering a 45ºC environment, Kaletra capsules became soft, sticky and broke apart when separated from each other, the researchers reported. At 35ºC capsules maintained their structure up to day 30, but became misshapen by day 60. Although drug content remained above 95% at both temperatures up to day 30, it had fallen below the acceptable limit of 85% by day 60, indicating that the drug might no longer be effective – even if patients were able to separate capsules from each other in order to take the correct dose.

The researchers recommend that Kaletra’s manufacturer should investigate storage of single capsules in blister packs to prevent clumping of capsules, and that if refrigeration is not possible pharmacies should avoid dispensing more than 30 days supply of Kaletra in hot climates.