nelfinavir
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Tratamiento de infección por VIH-1 en combinación con otros antirretrovirales.
Contraindicaciones
Absolutas
- Combinación con fármacos muy dependientes de CYP3A cuyo aumento puede causar eventos graves, y con inductores que eliminan eficacia, incluidos rifampicina, hipérico, alfuzosina, amiodarona, quinidina, pimozida, cisaprida, lurasidona, midazolam oral, derivados del ergot, triazolam, lovastatina, simvastatina y sildenafilo para hipertensión arterial pulmonar.
Advertencias clínicas
- Advertencia mayor · Puede causar diarrea importante; vigila hidratación y adherencia. También puede causar hiperglucemia y aumentar sangrado en hemofilia. — DailyMed, set_id e72c2bc6-9462-4a2e-8e1d-b97592376cbd
- Se han descrito eventos hepaticos, incluido fallo hepatico, durante el embarazo; la exposición a nelfinavir disminuye en el segundo y tercer trimestre. — DailyMed, set_id e72c2bc6-9462-4a2e-8e1d-b97592376cbd
Interacciones medicamentosas
- SeveraSustratos o moduladores de CYP3A/CYP2C19
Mecanismo: Pueden cambiar marcadamente concentraciones de nelfinavir o del fármaco concomitante.
Recomendación: Revisa las combinaciones contraindicadas y monitoriza o ajusta las permitidas.
DailyMed, set_id e72c2bc6-9462-4a2e-8e1d-b97592376cbd
- ModeradaDidanosina
Mecanismo: La administración conjunta puede interferir con la toma.
Recomendación: Administra nelfinavir con comida al menos 1 hora después o más de 2 horas antes de didanosina.
DailyMed, set_id e72c2bc6-9462-4a2e-8e1d-b97592376cbd
Eventos adversos
Comunes (≥1%)
Diarrea, náuseas, flatulencia y erupción
Raros pero graves
Hiperglucemia, cetoacidosis, hemorragia en hemofilia y reacciones cutáneas graves
Embarazo y lactancia
Considera un antirretroviral alternativo durante el embarazo por el riesgo hepatico y la menor exposición en el segundo y tercer trimestre. Si se usa nelfinavir, realiza vigilancia clínica estrecha. Evita la lactancia en personas con VIH tratadas.
Bibliografía reciente (PubMed)
Effective drugs with broad spectrum safety profile to all people are highly expected to combat COVID-19 caused by SARS-CoV-2. Here we report that nelfinavir, an FDA approved drug for the treatment of HIV infection, is effective against SARS-CoV-2 and COVID-19. Preincubation of nelfinavir could inhibit the activity of the main protease of the SARS-CoV-2 (IC50 = 8.26 μM), while its antiviral activity in Vero E6 cells against a clinical isolate of SARS-CoV-2 was determined to be 2.93 μM (EC50). In comparison with vehicle-treated animals, rhesus macaque prophylactically treated with nelfinavir had significantly lower temperature and significantly reduced virus loads in the nasal and anal swabs of the animals. At necropsy, nelfinavir-treated animals had a significant reduction of the viral replication in the lungs by nearly three orders of magnitude. A prospective clinic study with 37 enrolled treatment-naive patients at Shanghai Public Health Clinical Center, which were randomized (1:1) to nelfinavir and control groups, showed that the nelfinavir treatment could shorten the duration of viral shedding by 5.5 days (9.0 vs. 14.5 days, P = 0.055) and the duration of fever time by 3.8 days (2.8 vs. 6.6 days, P = 0.014) in mild/moderate COVID-19 patients. The antiviral efficiency and clinical benefits in rhesus macaque model and in COVID-19 patients, together with its well-established good safety profile in almost all ages and during pregnancy, indicated that nelfinavir is a highly promising medication with the potential of preventative effect for the treatment of COVID-19.
Multiple factors may affect combined antiretroviral therapy (cART). We investigated the impact of food, beverages, dietary supplements, and alcohol on the pharmacokinetic and pharmacodynamic parameters of 33 antiretroviral drugs. Systematic review in adherence to PRISMA guidelines was performed, with 109 reports of 120 studies included. For each drug, meta-analyses or qualitative analyses were conducted. We have found clinically significant interactions with food for more than half of antiretroviral agents. The following drugs should be taken with or immediately after the meal: tenofovir disoproxil, etravirine, rilpivirine, dolutegravir, elvitegravir, atazanavir, darunavir, lopinavir, nelfinavir, ritonavir, saquinavir. Didanosine, zalcitabine, zidovudine, efavirenz, amprenavir, fosamprenavir, and indinavir should be taken on an empty stomach for maximum patient benefit. Antiretroviral agents not mentioned above can be administered regardless of food. There is insufficient evidence available to make recommendations about consuming juice or alcohol with antiretroviral drugs. Resolving drug-food interactions may contribute to maximized cART effectiveness and safety. Múltiples factores pueden afectar la terapia antirretroviral combinada (cART). Investigamos el impacto de los alimentos, las bebidas, los suplementos dietéticos y el alcohol en los parámetros farmacocinéticos y farmacodinámicos de 33 medicamentos antirretrovirales. Se realizó la revisión sistemática en apego a las guías PRISMA, con 109 reportes de 120 estudios incluidos. Para cada fármaco se realizaron metanálisis o análisis cualitativos. Hemos encontrado interacciones clínicamente significativas con alimentos para más de la mitad de los fármacos antirretrovirales. Los siguientes medicamentos deben tomarse durante o inmediatamente después de comer: tenofovir, disoproxil, etravirina, rilpivirine, dolutegravir, elvitegravir, atazanavir, darunavir, lopinavir, nelfinavir, ritonavir, saquinavir. Didanosina, zalc
The transcription factor p53 is the most frequently impaired tumor suppressor in human cancers. In response to various stress stimuli, p53 activates transcription of genes that mediate its tumor-suppressive functions. Distinctive characteristics of p53 outlined here enable a well-defined program of genes involved in cell cycle arrest, apoptosis, senescence, differentiation, metabolism, autophagy, DNA repair, anti-viral response, and anti-metastatic functions, as well as facilitating autoregulation within the p53 network. This versatile, anti-cancer network governed chiefly by a single protein represents an immense opportunity for targeted cancer treatment, since about half of human tumors retain unmutated p53. During the last two decades, numerous compounds have been developed to block the interaction of p53 with the main negative regulator MDM2. However, small molecule inhibitors of MDM2 only induce a therapeutically desirable apoptotic response in a limited number of cancer types. Moreover, clinical trials of the MDM2 inhibitors as monotherapies have not met expectations and have revealed hematological toxicity as a characteristic adverse effect across this drug class. Currently, combination treatments are the leading strategy for enhancing efficacy and reducing adverse effects of MDM2 inhibitors. This review summarizes efforts to identify and test therapeutics that work synergistically with MDM2 inhibitors. Two main types of drugs have emerged among compounds used in the following combination treatments: first, modulators of the p53-regulated transcriptome (including chromatin modifiers), translatome, and proteome, and second, drugs targeting the downstream pathways such as apoptosis, cell cycle arrest, DNA repair, metabolic stress response, immune response, ferroptosis, and growth factor signaling. Here, we review the current literature in this field, while also highlighting overarching principles that could guide target selection in future combination treatment
The ultra-short-acting benzodiazepine remimazolam, approved for procedural sedation and general anesthesia, is inactivated by carboxylesterase 1 (CES1). Remimazolam´s involvement in CES1-mediated drug-drug interactions (DDIs) was investigated. Possible interactions of remimazolam were studied in co-exposure experiments with eleven different drugs. Further, substrates and inhibitors of CES1, identified in the literature, were evaluated for possible in-vivo inhibition using pharmacokinetic and Ki or IC50 values. Compounds with only one published inhibitory concentration and CES1 substrates lacking inhibition data were assigned conservative Ki values. In human liver homogenates and/or blood cells, remimazolam showed no significant inhibition of esmolol and landiolol metabolism, which, in turn, at up to 98 and 169 μM, respectively, did not inhibit remimazolam hydrolysis by human liver homogenates. In human liver S9 fractions, IC50 values ranged from 0.69 μM (simvastatin) and 57 μM (diltiazem) to > 100 μM (atorvastatin) and, for the remaining test items (bupropion, carvedilol, nelfinavir, nitrendipine, and telmisartan), they ranged from 126 to 658 μM. Remifentanil was ineffective even at 1250 μM. Guidance-conforming evaluation revealed no relevant drug-drug interactions with remimazolam via CES1. The algorithm-based predictions were consistent with human study data. Among CES1 inhibitors and substrates identified in the literature, only dapsone and rufinamide were found to be possible in-vivo inhibitors of remimazolam metabolism. Data and analyses suggest a very low potential of remimazolam for pharmacokinetic DDIs mediated by CES1. The theoretical approach and compiled data are not specific to remimazolam and, hence, applicable in the evaluation of other CES1 substrates.