Liver toxicity caused by nevirapine

Requena, Daniel González de; Núñez, Marina; Jiménez-Nácher, Inmaculada; Soriano, Vincent

doi:10.1097/00002030-200201250-00020

Cited by 155 publications

(80 citation statements)

References 4 publications

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“…Patients should therefore be carefully monitored for hepatotoxicity when highly active antiretroviral therapy (HAART) is commenced or changed. There is some evidence that the risk of early hepatotoxicity with nevirapine and high-dose ritonavir (RTV) (1000 mg/ day) is higher than with other ARTs [38,39] and nevirapine may also be linked to increased liver fibrosis [40], although not all studies show this [41]. High-dose RTV is no longer recommended in ART and low-dose RTV [in doses used to boost other protease inhibitors (PIs)] is not associated with significant liver problems.…”

Section: Antiretroviral Therapy and Hepatotoxicitymentioning

confidence: 99%

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

et al. 2009

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Section: Antiretroviral Therapy and Hepatotoxicitymentioning

confidence: 99%

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

et al. 2009

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“…Plasma NVP trough concentrations were increased by 34% and 22% following coadministration with 1,400 mg of FPV BID and 700 mg of FPV BID plus 100 mg of RTV BID, respectively, in this study. The magnitude of increase in NVP exposure observed in this study is unlikely to be clinically significant (2,3,5,6,9).…”

mentioning

confidence: 61%

Interaction between Fosamprenavir, with and without Ritonavir, and Nevirapine in Human Immunodeficiency Virus-Infected Subjects

DeJesus

Piliero

Summers³

et al. 2006

Antimicrob Agents Chemother

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Fosamprenavir (FPV) with and without ritonavir (RTV) was added to the antiretroviral regimens of human immunodeficiency virus-infected subjects receiving nevirapine (NVP) to evaluate this drug interaction. Significant reductions in plasma amprenavir exposure (25 to 35%) were observed following coadministration of 1,400 mg of FPV twice a day (BID) and 200 mg of NVP BID. A regimen of 700 mg of FPV BID plus 100 mg of RTV BID may be coadministered with NVP without dose adjustment.Fosamprenavir (FPV; GW433908) has been approved for the treatment of human immunodeficiency virus (HIV)-infected adult patients. FPV, the phosphate ester prodrug of the HIV-1 protease inhibitor amprenavir (APV), is rapidly and extensively converted to APV in vivo (11). Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that has demonstrated safety and efficacy in the treatment of HIV. Chronic administration of NVP leads to induction of cytochrome P450 (CYP450) metabolism (1). This study was designed to determine the steady-state drug-drug interaction between FPV and NVP. Because another NNRTI, efavirenz, was known to decrease APV exposure in other studies (4, 7, 10) and because of safety concerns with NVP in HIV-seronegative individuals (8), this study was conducted in HIV-infected subjects who were receiving and tolerating well an antiretroviral regimen of NVP and nucleoside reverse transcriptase inhibitors (NRTIs).Adult male and female HIV-infected subjects who had received stable antiretroviral regimens containing nevirapine at a dose of 400 mg/day for at least 12 weeks were eligible to participate if they had HIV RNA levels of Ͻ400 copies/ml at screening. Women had to be of non-childbearing potential or agree to acceptable contraceptive measures if they were of child-bearing potential. Breastfeeding and pregnant women were excluded. All subjects were informed of all aspects of the study and had to provide written informed consent approved by their local institutional review board prior to study participation. Subjects continued their prior NRTIs throughout the study, but other HIV-1 protease inhibitors and additional NNRTIs were prohibited.This study was conducted as an open-label, single-sequence, three-period, steady-state drug interaction study at three sites in the United States (GlaxoSmithKline [GSK] protocol APV10014). All subjects were receiving 200 mg of NVP twice a day (BID) in period 1. During period 2, 1,400 mg of FPV BID was added to the antiretroviral regimen and continued for 14 days. During period 3, the FPV dose was changed to 700 mg of FPV plus 100 mg of ritonavir (RTV) BID and continued for 14 days. There was no washout period between study treatments.On the final day of each treatment period, 15 serial wholeblood samples were collected over 12 h (t ϭ 0, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, and 12 h after the morning dose) for the determination of plasma NVP and APV concentrations. AUC (0-) (g · h/ml) 11.1 (9.11-13.6) 30.0 (24.7-36.4) 16.7 (14.8-18.8) 33.7 (31.5-36.1) 0.668 (0.5...

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“…Symptomatic hepatitis was observed in about 4% of patients treated with the drug [21]. Time of exposure to nevirapine [10,17,18] [10,14,22], and alcohol/ drug abuse [18,23] have all been associated with nevirapine toxicity. In our cohort we excluded all HIV-infected pregnant women with any of these risk factors for toxicity to better evaluate the role of nevirapine in drug-induced adverse events.…”

Section: Discussionmentioning

confidence: 99%

“…It usually appears in the first four weeks and may result in the development of StevensJohnson syndrome or toxic epidermal necrolysis [16]. Nevirapine may also cause hepatic toxicity ranging from asymptomatic hepatitis to acute liver necrosis and death [9,10,17,18].…”

mentioning

confidence: 99%

Nevirapine-induced side effects in pregnant women: experience of a brazilian university hospital

Kondo¹,

Carraro²,

Prandel³

et al. 2007

Braz J Infect Dis

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Nevirapine-based therapy is associated with increased frequency of adverse events among HIV-infected pregnant women. The aim of this article was to evaluate the incidence of adverse effects in HIV-infected women who started nevirapine during pregnancy. A retrospective study was performed in our center between January 2003 and December 2006 analyzing all women prescribed nevirapine during pregnancy. Women presenting any risk factor for hepatotoxicity were excluded from the analysis. Patients were divided into two groups according to the presence or absence of adverse effects, and a correlation to CD4 counts was performed. Liver function abnormality was graded according to the Division of AIDS toxicity guidelines. A total of 170 women initiated nevirapine during pregnancy, but only 133 were included in the study. Twenty-seven women (20.3%) presented adverse effects, skin rash accounting for 77.8% (21/27 women) and liver function abnormalities for 22.2% (6/27) of the cases. Baseline CD4 counts, viral loads and transaminases were similar in both groups. All nevirapine side effects were developed in less than seven weeks. Four of 31 women with CD4 counts <250 cells/μ μ μ μ μL (12.9%) and 23 of 102 women with CD4 counts ≥ ≥ ≥ ≥ ≥250 cells/μ μ μ μ μL (22.5%) developed adverse events. All patients who experienced hepatotoxicity had pretreatment CD4 counts ≥ ≥ ≥ ≥ ≥250cells/ μ μ μ μ μL. The incidence of adverse events with nevirapine in our study was high, but most of them were cutaneous. There was no correlation between high CD4 counts and adverse events when analyzing both cutaneous and hepatic reactions; nevertheless, hepatotoxicity occurred only in pregnant women with CD4 counts ≥ ≥ ≥ ≥ ≥250cells/μ μ μ μ μL.

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Liver toxicity caused by nevirapine

Cited by 155 publications

References 4 publications

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

Interaction between Fosamprenavir, with and without Ritonavir, and Nevirapine in Human Immunodeficiency Virus-Infected Subjects

Nevirapine-induced side effects in pregnant women: experience of a brazilian university hospital

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