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Conference
"Managing Complex Drug Interactions: Challenges in the Real World" Dr. Alice Tseng (biography) English - 2006-03-30 - 56 minutes
(46 slides)
Summary : As the number of available HIV drugs increases, so does the potential for serious drug interactions. Interactions may result in reduced drug concentrations/effectiveness, and/or increased side effects.
One such interaction outlined in this presentation is the effect of gastric modifying agents on the bioavailability of atazanavir. Although still debatable, some studies have shown that as the gastric PH increases, there is a significant decline in the bioavailability of atazanavir. Dr. Tseng cautions the substantial variability in studies attempting to delineate the clinical significance of this particular drug interaction. Some studies fail to note the use of other antiretroviral agents such as tenofovir which may have an effect. As well, patient histories vary considerably, as does the types of gastric modifiers administered. Dr. Tseng outlines these and a few other parameters, such as pharmacogenomics, that should be taken into consideration when clinically assessing the effect of gastric modifiers on the bioavailability of atazanavir.
In some cases, individuals may be intolerant to ritonavir, therefore necessitating alternative PI regimens which do not require boosting. However, it is important to recognize that combining PIs may also have considerable interaction. In the instance of atazanavir, its bioavailability is reduced significantly when in combination with tenofovir. Since a boosted regimen may not always be a feasible option, Dr. Tseng evaluates the effects of a timely administration of these PIs or an increased dosage of atazanavir. Furthermore, she presents alternative PI combinations describing their benefits and drawbacks.
Other known PI interactions involve tipranavir and have been shown in 2 studies (Harris et al., Peytavin et al.). In these studies, tipranavir significantly reduced concentrations of lopinavir and fosamprenavir, respectively. Interestingly, tipranavir concentrations were affected when taken in combination with enfuvirtide, a fusion inhibitor.
Dr. Tseng concludes by reviewing possible interactions of new agents: CCR5 antagonists, integrase inhibitors, darunivir (a PI), and entravirine (an NNRTI).
Learning objectives : After viewing this presentation, participants will be able to discuss the management of common drug interactions shown with:
- Atazanavir and gastric-acid modifiers;
- Dual PI combinations;
- Tipranavir;
- New antiretroviral agents.
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