12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 668

Shahin Lockman^1,2, P Ndase², D Holland³, R Shapiro^2,4, J Connor³, and E Capparelli^3
1Brigham and Women's Hosp, Boston, MA, USA; ²Botswana-Harvard Sch of Publ Hlth AIDS Initiative Partnership, Gaborone; ³Univ of California, San Diego, USA; and ⁴Beth Israel Deaconess Med Ctr, Boston, MA, USA

BACKGROUND: Refrigeration is recommended for didanosine (ddI) and stavudine (d4T) pediatric oral solutions and Kaletra (LPV/RTV) capsules, but data are lacking regarding their stability at non-refrigerated temperatures. These drugs are increasingly prescribed for patients in the developing world, many of whom lack access to refrigeration and live in climates with temperatures that can exceed 40°C. We examined the stability of these 3 drug formulations after storage under experimental conditions for as long as 11 weeks at temperatures up to 55°C.

METHODS: ddI and d4T were reformulated according to manufacturers’ instructions. For each drug, 1-mL aliquots were kept at 4°C, 15°C (d4T only), 25°C, 35°C, 45°C, and 55°C. At each temperature, ddI and d4T stability was tested on day 1, and at 1, 2, 4, and 8 weeks. LPV and RTV were assayed from Kaletra capsules stored at these same temperatures for 11 weeks. At each temperature and time point, 3 aliquots were tested. ddI and d4T were assayed using reversed-phase high-pressure liquid chromatography (HPLC), and Kaletra with mobile-phase HPLC. The 3 results were averaged; the average area of drug peak at 1 temperature and time point is expressed as a percentage difference from the drug peak area of stock solution kept at 4°C for the same time point.

RESULTS: ddI was stable through week 4 at temperatures as high as 45°C. At week 8, the change in ddI drug peak area compared with the 4°C control was negligible at 35°C or less, but was –16.0% at 45°C and –58.1% at 55°C. d4T was stable at 8 weeks only if stored at 10°C or cooler (d4T drug peak area was –18.9% after 8 weeks at 15°C). At 2 weeks, the d4T drug peak area compared with 4°C control was –16.6% and –83.9% for drug stored at 25°C and 35°C, respectively. After 4 weeks at these temperatures, the d4T drug peak area was –31.3% and –95.8%, respectively (and at 8 weeks, –52.8% and –99.9%). For Kaletra, LPV and RTV loss was negligible for temperatures as high as 35°C at 11 weeks. At 11 weeks, LPV drug peak area was –13.1% at 45°C and –18.2% at 55.0°C, and RTV drug peak area was –42.5% at 45°C and –61.3% at 55°C.

CONCLUSIONS: Pediatric oral solutions of ddI are stable at temperatures as high as 35°C for 8 weeks; d4T solutions, however, show significant loss of stability after 4 weeks at 25°C, and the majority of drug is lost after even 1 week at 35°C. The LPV component of Kaletra is stable at temperatures as high as 45°C for 11 weeks, and the RTV component is stable at temperatures as high as 35°C for 11 weeks.

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Copyright © 2005 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.