Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of human immunodeficiency virus disease. To establish its safety profile, we conducted a review of data from prospective US and international clinical trials involving a total of 906 adult patients and 468 pediatric patients treated with NVP. Drug-related adverse events were similar in adults and children, with rash and nausea most frequently reported in adults and rash and granulocytopenia most frequently reported in children. A separate analysis of rash based on data from adult patients in controlled trials demonstrated a 16% rate of NVP-attributable rash in these patients. Of patients with NVP-associated rash, 65% developed rash within the first 6 weeks of therapy, and it has been shown that a lower lead-in dose (200 mg/d vs the standard 400 mg/d) for the first 2 weeks of NVP treatment reduces the frequency of drug-associated rash. Serious rash (Stevens-Johnson syndrome [SJS] or SJS/toxic epidermal necrolysis transition syndrome) occurred with an incidence of 0.3% and clinical hepatitis with an incidence of 1.0% among NVP-treated patients in clinical trials. Adverse event data from long-term clinical trials demonstrated a lower incidence of NVP-related adverse events than in short-term trials of NVP therapy. An analysis of abnormal laboratory findings using thresholds similar to those found in the prescribing information for other commonly used antiretroviral agents and data from controlled trials in adults showed that the most frequently observed laboratory abnormalities were elevations in liver function test results. Approximately 50,000 patients in the United States had been treated with marketed NVP at the time of writing, and postmarketing surveillance has supported the overall safety profile observed in clinical trials. NVP has been shown to be well tolerated in both adult and pediatric patients.
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PMID:Safety profile of nevirapine, a nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection. 991 3

Nevirapine is a non-nucleoside reverse transcriptase inhibitor widely used in combination with other antiretroviral agents for the treatment of HIV infection. Severe rash, including the Stevens-Johnson syndrome (SJS), is the major toxicity of nevirapine and is described in the package labeling with a prominent, boxed warning. Though physicians treating large populations of patients with HIV are well aware of this complication, only one other report of nevirapine-associated SJS has been documented in the dermatology literature. We describe 2 cases of SJS related to nevirapine use and review the literature on this newly recognized association.
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PMID:Stevens-Johnson syndrome caused by the antiretroviral drug nevirapine. 1117 14

The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus. All patients had a CD4+ T-lymphocyte count of less than 100 cells/microl at study entry. Efficacy in this single-arm open-label prospective study was analyzed on an as-treated basis. No patient received highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. PCP developed in four patients, one of whom had been noncompliant. No PCP episode occurred in the first year. Probabilities of freedom from PCP were 0.97 (95%CI, 0.92-1) after 24 months and 0.93 (95%CI, 0.84-1) after 36 months. Of 74 (69.8%) patients positive for anti-toxoplasma IgG antibodies, one noncompliant patient developed toxoplasmic encephalitis after 24 months. Allergic reactions were observed in 18 (17%) patients and resulted in permanent discontinuation in 7 (6.6%) patients. One (0.9%) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction (Stevens-Johnson syndrome). The median survival of study participants was 29 months, with relentless progression of AIDS accounting for most deaths. The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance. Efficacy and safety compare favorably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens.
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PMID:Effectiveness of twice-weekly pyrimethamine-sulfadoxine as primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in patients with advanced HIV infection. 1207 19

Patients infected with human immunodeficiency virus are highly susceptible to adverse dermatological reactions to specific medications. Severe cutaneous conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis are associated with high morbidity and, notably for toxic epidermal necrolysis, high mortality. Although overall mortality from human immunodeficiency virus has dramatically declined owing to highly active antiretroviral therapy, these antiretroviral regimens have been associated with a wide spectrum of severe cutaneous reactions. We reviewed case reports and clinical trials in the English literature on Medline (1966 to 2001) and Aidsline (1980 to 2000) to determine the prevalence of Stevens-Johnson syndrome and toxic epidermal necrolysis attributable to the current FDA approved antiretroviral medications. We identified a total of approximately 50 patients who had Stevens-Johnson syndrome and/or toxic epidermal necrolysis associated with the use of 5 antiretroviral medications: 2 nucleoside reverse transcriptase inhibitors, zidovudine (2 patients) and didanosine (1 patient); 1 non-nucleoside reverse transcriptase inhibitor, nevirapine (42 patients); and 2 protease inhibitors, indinavir (1 patient) and amprenavir (an unspecified number within the 1% of over 1400 patients experiencing severe life-threatening reactions). Of the reports that specified the onset time of adverse reaction after initiation of treatment, 86% (19/22) of patients experienced reactions within 4 weeks. Ten of the approximately 50 patients were diagnosed with Stevens-Johnson syndrome or toxic epidermal necrolysis, due to specific antiretroviral medication, or a combination of medications identified by either resolution upon withdrawal, consistent biopsy findings or a positive rechallenge. The remainder of the identified patients were reported in articles lacking data regarding drug administration, reaction history or other details.
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PMID:Severe cutaneous reactions associated with the use of human immunodeficiency virus medications. 1263 14

CIRCUMSTANCES AND CHARACTERISTICS: The risk of toxiderma is greater in patients infected by the human immunodeficiency virus (HIV). The most common toxidermas are maculopapular exanthema and drug hypersensitivity reactions. These toxidermas are predominantly observed with non-nucleoside reverse transcriptase analogs (nevirapine, efavirenz) and abacavir. Toxiderma has also been observed with other nucleoside reverse transcriptase analogs (zalcitabine) and protease inhibitors. REGARDING SEVERITY: The toxidermas observed are usually benign (maculopapular exanthema) and do not always require suspension of the treatment. However, certain toxidermas (Stevens-Johnson syndrome, Lyell syndrome and drug hypersensitivity syndrome) may be life-threatening and therefore contraindicate the continuation of treatment and also its sudden reintroduction. PREVENTION AND PRACTICAL APPROACH: Several studies have assessed the risk factors for toxiderma induced by nevirapine and hypersensitivity reactions to abacavir. The practical approach varies depending on the drug responsible, the clinical form of the toxiderma and the possible alternatives.
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PMID:[Antiretroviral-induced toxiderma in HIV-infected patients]. 1450 44

Despite the decrease in opportunistic infections associated with HIV in the highly active antiretroviral treatment (HAART) era, a significant number of patients still present with skin pathology, some of which can be attributed directly or indirectly to antiretroviral therapy. The non-nucleoside reverse transcriptase inhibitors exhibit a class effect with regard to skin adverse manifestations, and the spectrum of disease can vary from a mild morbilliform rash to Stevens-Johnson syndrome. Certain protease inhibitors are associated with rash, and indinavir causes retinoid-like manifestations such as paronychia, alopecia, ingrown toe-nails, and curling of straight hair. Abacavir, a nucleoside reverse transcriptase inhibitor, is notorious for causing a hypersensitivity reaction in select patients. The fusion inhibitor enfuvirtide causes injection-site reactions in the overwhelming majority of patients, although a new method of delivery has decreased the rate and severity of these reactions. A syndrome of lipoatrophy with or without lipohypertrophy, often termed lipodystrophy, has been described in patients receiving HAART. Potential management of lipoatrophy includes switching antiretrovirals and surgical treatment with facial fillers. Lastly, skin manifestations of the immune reconstitution inflammatory syndrome, including herpes zoster and warts, must be recognized and treated accordingly. In the evaluation of the individual HIV-infected patient receiving antiretroviral therapy who presents with a skin disorder, clinicians should consider the CD4 cell count as a marker of the degree of immunodeficiency, the specific antiretrovirals used, and the timing of the initiation of antiretroviral therapy in order to formulate a rational differential diagnosis. Management should be individualized based on the specific drug that is implicated and the severity of the reaction.
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PMID:Dermatologic adverse effects of antiretroviral therapy: recognition and management. 1764 77

Nevirapine is a non-nucleoside reverse transcriptase inhibitor commonly used in human immunodeficiency virus-1 multidrug regimens and associated with life-threatening cutaneous reactions. Here, we report the successful use of intravenous immunoglobulin in a pediatric patient with Stevens-Johnson syndrome and highlight the risk of nevirapine usage in human immunodeficiency virus postexposure prophylaxis.
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PMID:Nevirapine-induced Stevens-Johnson syndrome in a pediatric patient. 1830 77

HIV-infected patients have a higher risk of developing cutaneous reactions than the general population, which has a significant impact on patients' current and future care options. The severity of cutaneous adverse reactions varies greatly, and some may be difficult to manage. HIV-infected patients just at the beginning of antiretroviral treatment can frequently show a wide variety of adverse drug effects such as drug rashes, hyperpigmentation, hair loss, hypersensitivity reactions, injection site reaction, urticarial reaction, erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome. The early detection and treatment of cutaneous adverse drug reactions, plus identification of the causative agent, are essential to prevent the progression of the reaction, preventing additional exposures and ensuring the appropriate use of medications for the current condition and keeping in mind others, such as patient age. This article emphasizes the most common features of an antiretroviral drug-induced cutaneous reaction from protease inhibitors, non-nucleoside analogue reverse transcriptase inhibitors, fusion inhibitors, nucleoside reverse transcriptase inhibitors, integrase inhibitors and inhibitors of the CCR5 chemokine receptor, paying special attention to the newest drugs approved for the treatment of HIV infection, such as tipranavir, darunavir, etravirine, enfuvirtide, raltegravir and maraviroc.
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PMID:Adverse cutaneous reactions associated with the newest antiretroviral drugs in patients with human immunodeficiency virus infection. 1865 88

Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is widely prescribed as a part of the combination therapy of human immunodeficiency virus (HIV) infection because of its efficacy and good tolerability. Here, we report a case of Stevens-Johnson syndrome (SJS) secondary to nevirapine. The patient had a diffuse, exfoliating exanthema with generalized bullous eruptions that involved the face, trunk and both extremities with elevated hepatic alanine aminotransferase and aspartate aminotransferase enzyme activities. The condition improved with stoppage of nevirapine-based highly active antiretroviral therapy (HAART) regimen, so we attributed this adverse event to nevirapine. A strict vigilance of adverse drug reaction is required in HAART.
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PMID:Nevirapine induced Stevens-Johnson syndrome in an HIV infected patient. 2145 32

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are the most Severe Cutaneous Adverse Reactions (SCARs) which mainly caused by exposure to drugs and having significant morbidity and mortality. TEN represents an immunologic reaction to a foreign antigen and is most often caused by drugs. Nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor (NNRTI) is an important component of Highly Active Antiretroviral Therapy (HAART). It is sometimes associated with life-threatening adverse reactions. Here, we report the fatal case of 72-year-old male who developed TEN secondary to intake of nevirapine. This fatal case report will increase awareness among treating physicians for careful monitoring of patients on NNRTI-based antiretroviral therapy and better counseling of the patient on NVP regimen for early identification and reporting of SCARs so that fatalities due to adverse drug reactions can be prevented with timely intervention.
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PMID:Fatal Nevirapine-Induced Toxic Epidermal Necrolysis in a HIV Infected Patient. 2713 91


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