Side-effects Associated With the use of Nevirapine in Treatment-naïve
Objectives: A warning about the use of nevirapine (NVP) by its pharmaceutical manufacturer has been issued in which it has been recommended that NVP should not be prescribed in patients with increased risk of toxicity based on CD4 cut-offs and gender. The aim of this study was to determine whether these recommendations are of use in preventing side effects.
Methods: This retrospective study included antiretroviral drug-nave patients who started treatment with NVP. Patients were divided into two groups: those with high CD4 counts (H; women: CD4 count >250cells/μL; men: CD4 count >400cells/μL) and those with low CD4 counts (L; women: CD4 count <250cells/μL; men: CD4 count <400cells/μL).
Results: A total of 142 patients were included in the study, 61 in the H group and 81 in the L group. Skin rash developed in 6.56% of patients [95% confidence interval (CI) 2.67–15.70%] in the H group and in 14.81% of patients (95% CI 8.72–24.17%) in the L group (P=0.18). Hepatotoxicity developed in 4.92% (95% CI 1.79–13.50%) and 6.17% (95% CI 2.73–13.66%) of patients with high and low CD4 cell counts, respectively (P=1.0).
Conclusion: The recommendations not to use NVP in drug-nave patients at increased risk of toxicity on the basis of gender and CD4 cell count do not seem to be of use in preventing the occurrence of side effects. However, a small number of patients were included in this study, and hence the possibility cannot be excluded that the recommendations are appropriate in another clinical practice setting.
Nevirapine (NVP) was the first nonnucleoside reverse transcriptase inhibitor approved for use in HIV-infected patients and is a widely used antiretroviral drug, the efficacy of which has been well demonstrated in numerous clinical trials. It is easy to administer and is generally well tolerated. The main limitation of its use is the risk of the occurrence of potentially serious side effects, such as hepatic toxicity and hypersensitivity reactions.
In order to avert or reduce such reactions, an attempt has been made to identify the risk factors for presentation of hypersensitivity reactions or hepatotoxicity. In a retrospective analysis of Boehringer-Ingelheim databases, it was found that the risk of symptomatic hepatotoxicity was 12 times greater in women with a CD4 count above 250cells/μL, in comparison with women with a CD4 count below 250cells/μL (11 vs. 0.9%). In men, there was a 6.3% risk if the CD4 count was above 400cells/μL, compared with 1.2% when the CD4 count was below 400cells/μL. In the case of hepatotoxicity with skin rash, the increased risk was 9.8 (relative risk) for women with a CD4 count above 250cells/μL and 6.4 (relative risk) for men with a CD4 count above 400cells/μL. These data are clinically significant and appear in the Summary of Product Characteristics, where direct reference is made to the use of this drug in the described conditions, with the recommendation that it should only be used in clinical situations where the benefits clearly outweigh the risks. This warning about NVP also appears in the guidelines for antiretroviral treatment; the purpose of the warning is to decrease the frequency of symptomatic liver toxicity.
Analysis of the results of a large randomized clinical trial, the 2NN study, demonstrated that the rate of skin rash and hepatic events was higher in patients with CD4 counts >200cells/μL, and also that women with CD4 counts >200cells/μL had a statistically significantly increased risk of developing a rash compared with men. In the EuroSIDA cohort study, in which the risk of NVP discontinuation in relation to high and low CD4 cell counts was investigated, it was observed that patients with a high CD4 cell count had an increased risk of discontinuation compared with patients with a low CD4 cell count, and the risk was higher in nave patients.
The aim of this study was to determine whether or not these gender- and CD4 cell count-based recommendations are of use in preventing the side effects associated with NVP treatment.
Abstract and Introduction
Abstract
Objectives: A warning about the use of nevirapine (NVP) by its pharmaceutical manufacturer has been issued in which it has been recommended that NVP should not be prescribed in patients with increased risk of toxicity based on CD4 cut-offs and gender. The aim of this study was to determine whether these recommendations are of use in preventing side effects.
Methods: This retrospective study included antiretroviral drug-nave patients who started treatment with NVP. Patients were divided into two groups: those with high CD4 counts (H; women: CD4 count >250cells/μL; men: CD4 count >400cells/μL) and those with low CD4 counts (L; women: CD4 count <250cells/μL; men: CD4 count <400cells/μL).
Results: A total of 142 patients were included in the study, 61 in the H group and 81 in the L group. Skin rash developed in 6.56% of patients [95% confidence interval (CI) 2.67–15.70%] in the H group and in 14.81% of patients (95% CI 8.72–24.17%) in the L group (P=0.18). Hepatotoxicity developed in 4.92% (95% CI 1.79–13.50%) and 6.17% (95% CI 2.73–13.66%) of patients with high and low CD4 cell counts, respectively (P=1.0).
Conclusion: The recommendations not to use NVP in drug-nave patients at increased risk of toxicity on the basis of gender and CD4 cell count do not seem to be of use in preventing the occurrence of side effects. However, a small number of patients were included in this study, and hence the possibility cannot be excluded that the recommendations are appropriate in another clinical practice setting.
Introduction
Nevirapine (NVP) was the first nonnucleoside reverse transcriptase inhibitor approved for use in HIV-infected patients and is a widely used antiretroviral drug, the efficacy of which has been well demonstrated in numerous clinical trials. It is easy to administer and is generally well tolerated. The main limitation of its use is the risk of the occurrence of potentially serious side effects, such as hepatic toxicity and hypersensitivity reactions.
In order to avert or reduce such reactions, an attempt has been made to identify the risk factors for presentation of hypersensitivity reactions or hepatotoxicity. In a retrospective analysis of Boehringer-Ingelheim databases, it was found that the risk of symptomatic hepatotoxicity was 12 times greater in women with a CD4 count above 250cells/μL, in comparison with women with a CD4 count below 250cells/μL (11 vs. 0.9%). In men, there was a 6.3% risk if the CD4 count was above 400cells/μL, compared with 1.2% when the CD4 count was below 400cells/μL. In the case of hepatotoxicity with skin rash, the increased risk was 9.8 (relative risk) for women with a CD4 count above 250cells/μL and 6.4 (relative risk) for men with a CD4 count above 400cells/μL. These data are clinically significant and appear in the Summary of Product Characteristics, where direct reference is made to the use of this drug in the described conditions, with the recommendation that it should only be used in clinical situations where the benefits clearly outweigh the risks. This warning about NVP also appears in the guidelines for antiretroviral treatment; the purpose of the warning is to decrease the frequency of symptomatic liver toxicity.
Analysis of the results of a large randomized clinical trial, the 2NN study, demonstrated that the rate of skin rash and hepatic events was higher in patients with CD4 counts >200cells/μL, and also that women with CD4 counts >200cells/μL had a statistically significantly increased risk of developing a rash compared with men. In the EuroSIDA cohort study, in which the risk of NVP discontinuation in relation to high and low CD4 cell counts was investigated, it was observed that patients with a high CD4 cell count had an increased risk of discontinuation compared with patients with a low CD4 cell count, and the risk was higher in nave patients.
The aim of this study was to determine whether or not these gender- and CD4 cell count-based recommendations are of use in preventing the side effects associated with NVP treatment.
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