Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atazanavir is the first once-daily protease inhibitor for the treatment of human immunodeficiency virus type 1 infection and should be used only in combination therapy, as part of a highly active antiretroviral therapy (HAART) regimen. In addition to being the most potent protease inhibitor in vitro, atazanavir has a distinct cross-resistance profile that does not confer resistance to other protease inhibitors. However, resistance to other protease inhibitors often confers clinically relevant resistance to atazanavir. Currently, atazanavir is not a preferred protease inhibitor for initial HAART regimens. In treatment-naive patients, atazanavir can be given as 400 mg/day. However, atazanavir should be pharmacologically boosted with ritonavir in treatment-experienced patients or when coadministered with either tenofovir or efavirenz. Patients who receive atazanavir experience similar rates of adverse events compared with patients receiving comparator regimens. An exception is an increased risk of asymptomatic hyperbilirubinemia, which is due to competitive inhibition of uridine diphosphate-glucuronosyltransferase 1A1. Although hyperbilirubinemia is a common adverse drug reaction of atazanavir therapy (22-47%), fewer than 2% of patients discontinue atazanavir therapy because of this adverse effect. Common adverse effects reported with atazanavir include infection, nausea, vomiting, diarrhea, abdominal pain, headache, peripheral neuropathy, and rash. Of significance, fewer abnormalities have been observed in plasma lipid profiles in patients treated with atazanavir compared with other protease inhibitor-containing regimens. As with other protease inhibitors, atazanavir is also a substrate and moderate inhibitor of the cytochrome P450 (CYP) system, in particular CYP3A4 and CYP2C9. Clinically significant drug interactions include (but are not limited to) antacids, proton pump inhibitors, histamine type 2 receptor antagonists, tenofovir, diltiazem, irinotecan, simvastatin, lovastatin, St. John's wort, and warfarin. We conclude that atazanavir is a distinctively characteristic protease inhibitor owing to its in vitro potency, once-daily dosing, distinct initial resistance pattern, and infrequent association with metabolic abnormalities.
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PMID:Atazanavir for the treatment of human immunodeficiency virus infection. 1558 41

Most ritonavir-boosted protease inhibitor (PI)-based antiretroviral regimens offer comparable levels of virological efficacy. Thus, the tolerability of the regimen becomes a distinguishing factor with implications for patient quality of life (QoL), treatment adherence, and clinical outcome. This article describes results from the CASTLE study (comparing once-daily atazanavir/ritonavir [ATV/RTV] with twice-daily lopinavir/ritonavir [LPV/RTV], both in combination with fixed-dose tenofovir/emtricitabine, in treatment-naive HIV-infected patients) and an evaluation of the impact of gastrointestinal (GI) complications of treatment on patient QoL, as measured by the irritable bowel syndrome (IBS) QoL questionnaire (IBS-QoL). Changes in IBS-QoL from baseline over time (to week 24) were classified as: "Improvement" (> or =2-point positive change from baseline), "No change" (<2-point change), or "Worsening" (> or =2-point negative change). Data were collected on GI adverse events (AEs) and use of GI medications. Of the 599 patients with IBS-QoL-evaluable data through week 24, fewer patients in the ATV/RTV group than in the LPV/RTV group experienced grade 2-4 treatment-related GI AEs including diarrhea (3% versus 10%), nausea (5% versus 7%), and vomiting (<1% on both arms). Nearly three times as many patients receiving LPV/RTV used GI medications. ATV/RTV was associated with an increase in overall IBS-QoL scores and more patients receiving ATV/RTV than LPV/RTV experienced improvement in IBS-QoL through week 24. In contrast to LPV/RTV, ATV/RTV treatment was associated with earlier and more positive improvements in QoL scores across CD4 sub-groups. Differences in the health-related QoL profile between ATV/RTV and LPV/RTV may be important when selecting PI-based antiretroviral regimens.
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PMID:Gastrointestinal tolerability and quality of life in antiretroviral-naive HIV-1-infected patients: data from the CASTLE study. 2046 43