Newar Giraldo

Interacciones medicamentosas: aproximación para establecer y evaluar su relevancia clínica

La identificacion, prevencion y tratamiento de las interacciones medicamentosas clinicamente relevantes son aspectos fundamentales en la farmacoterapia. En este trabajo se ha pretendido sistematizar la informacion y desarrollar una propuesta para establecer y evaluar la relevancia clinica de las interacciones medicamentosas. Se realizo una revision bibliografica en Medline y PubMed, y en las referencias de los articulos considerados relevantes. En los titulos y resumenes de los articulos se busco el termino «interacciones medicamentosas» combinado con «relevante clinicamente», «relevancia clinica» o «relevante significativamente». Se incluyeron las publicaciones realizadas en humanos, en ingles o espanol, entre enero de 1996 y junio de 2006. Se presentan el tipo y mecanismo de las interacciones medicamentosas, especialmente las asociadas a cambios en el aclaramiento sistemico y en la biodisponibilidad; se propone una secuencia de pasos a seguir para establecer la relevancia clinica de las interacciones y una clasificacion basada en la gravedad y probabilidad de aparicion.

Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

BackgroundHighly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection.Methods/designRandomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals.DiscussionPreliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required.Trial registrationRegistration number NCT00721305.

Interacciones medicamentosas en pacientes infectados con el VIH: aproximación para establecer y evaluar su relevancia clínica

Objetivo: Sistematizar informacion sobre interacciones medicamentosas en pacientes con VIH/sida, y verificar la funcionalidad de una propuesta para definir y evaluar la relevancia clinica de las interacciones, especialmente las farmacocineticas. Metodo: Se realizo una revision en PubMed de articulos publicados en ingles o espanol, entre enero de 1995 y junio de 2007, sobre interacciones de antirretrovirales en humanos. La estrategia de busqueda fue: drug interactions and anti-retroviral agents (or drugs), en el titulo y resumen. La busqueda fue complementada con la revision de interacciones de medicamentos utilizados frecuentemente en pacientes con VIH/sida y de referencias de articulos considerados relevantes. Finalmente, se siguio una propuesta para definir y evaluar la relevancia clinica, basada en la probabilidad de ocurrencia y en la gravedad de la interaccion. Resultados: Se identificaron 378 articulos, de los que se pudo acceder al texto completo de 296. Para pacientes con VIH/sida, se desarrollo el tipo y mecanismo de las interacciones; se evaluo y definio la relevancia clinica de las interacciones, con base a una propuesta definida previamente. Entre las interacciones farmacocineticas de relevancia clinica, cerca de un 80% estuvieron relacionadas con cambios en el aclaramiento sistemico [debidos a la inhibicion o a la induccion sistemica de la actividad metabolica del citocromo P-450 3A4 (CYP3A4)]; mientras que un 15% con cambios en la biodisponibilidad [variaciones en el pH gastrointestinal, en el aclamiento presitemico (mediado por la CYP3A4) o en la actividad de la glicoproteina-P (Gp-P)]. Conclusiones: En los pacientes infectados con el VIH/sida, la mayoria de las interacciones farmacocineticas de relevancia cinica se deben a la inhibicion o induccion de la actividad metabolica sistemica del higado.

Relevancia clínica de las interacciones medicamentosas en pacientes infectados con el virus de la inmunodeficiencia humana: actualización 2009-2014

OBJECTIVE To update information about drug interactions in patients with HIV/AIDS. METHODS Comprehensive literature review in MEDLINE/PubMed database from May of 2009 to December of 2014, using the Mesh terms: Anti-retroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full text were retrieved. Additionally, citation lists from identified articles were reviewed. The study inclusion was assessed by three independent researchers and by consensus among them when was necessary. Clinical relevance of drug interaction was grouped into four levels according to seriously and probability of occurrence. RESULTS Global, 546 different references were retrieved and 243 were selected. In addition 11 further manuscripts were identified in the references of the included articles. Overall, 935 pairs of drug interactions were identified, 95.7% pharmacokinetic (823 by enzyme induction or inhibition and 67 by changes in bioavailability). Of the 935 pairs of drug interactions, 402(43%) were classified as levels 1 or 2. CONCLUSIONS The most clinically relevant antiretroviral drug interactions are due to pharmacokinetic mechanism, mainly induction or enzyme inhibition, according to previous reviews, the protease inhibitors remain as the antiretrovirals with the highest number of clinical relevant interactions.

Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS

Background: Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. Objective: The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Methods: A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Results: Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug‐drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV®) was developed. Conclusions: A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS.

Approach to establishing and evaluating clinical relevance of drugs interactions in HIV patients: 2009 update

Abstract Objective To update information on drug interactions in patients with HIV/AIDS. Method PubMed was used to review English and Spanish articles published between 1 July 2007 and 30 April 2009 on antiretroviral drug interactions in humans. The search included a review of interactions between commonly-used medications in patients with HIV/AIDS and references from articles considered to be relevant. Results Fifty two new interactions were identified having to do with CYP3A4 metabolism and competition for intestinal absorption. New pharmacokinetic interactions were identified for medications that were already on the market, and we report interactions for drugs that were recently introduced: Tipranavir, Fosamprenavir, Darunavir, Raltegravir, Maraviroc and Etravirine. Conclusions There is evidence of 52 new interactions between medications using metabolic routes in the CYP450 enzymatic system, and an explanation is given for others in the intestinal absorption process.