Didanosine (ddI Sample Clauses

Didanosine (ddI ddI-EC, Videx®) Didanosine is an acid-labile antiretroviral NRTI; the tablet formulation of ddI includes antacids to prevent acid hydrolysis of the drug in the stomach. In most studies, the 400-mg QD dose has demonstrated both pharmacokinetic and virologic equivalence and similar toxicity rates to the 200-mg BID dose through week 24. Results from study AI454-148, however, indicated an inferior virologic response at 48 weeks in patients on a regimen of ddI, ZDV, and NFV compared with patients on a regimen of ZDV, 3TC, and NFV. The proportions of patients with HIV-1 RNA <400 copies/mL were 50% and 59%, respectively, while the proportions of those with HIV-1 RNA <50 copies/mL were 34% and 47%, respectively. CD4+ cell counts were comparable between the two arms. The most common AEs associated with ddI are gastrointestinal upset, peripheral neuropathy, and pancreatitis. In addition, an enteric-coated (EC) capsule of ddI is available. The capsule does not require the buffering used in the tablet formulation. Pharmacokinetic studies comparing the EC capsule to the buffered tablets indicate that the AUCs are equivalent, the Cmax of the EC formulation is 60% of the Cmax of the tablets, and the median Tmax values are 2.33 hours for the EC formulation and 0.67 hours for the tablets (Xxxxxxx-Xxxxx Squibb communication/ Videx package insert). Gamma scintigraphy indicates the delay in Tmax is related to the time needed to dissolve the capsule in the stomach, and that absorption is rapid once the drug enters the small intestine. In healthy volunteers, following a high-fat meal, mean AUC was reduced 19%, Cmax was reduced 46%, and Tmax was increased from 2.00 hours (fasting) to 5.25 hours (fed). Therefore, the same restrictions on food intake apply to the EC capsules as to the tablets. Overall, participants on the EC formulation have experienced similar rates of gastrointestinal toxicity (primarily diarrhea) as those on tablets. Clinicians should use caution when coadministering TDF, ddI EC, and either NVP or EFV in treatment-naïve HIV patients with high baseline viral loads. Results from two recently conducted, investigator-sponsored trials by Xxxxxxxxxx et al. (the ININ Study) and Xxxxxx (X.X. Xxxxxxx’s written communication to BMS) have demonstrated a potential for early virologic failure associated with this antiretroviral regimen in treatment-naïve HIV patients with high baseline viral loads. The ININ Study [Podzamczer, 2004] is an open-label, randomized, multicenter ...
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Related to Didanosine (ddI

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