tipranavir
Sources réglementaires consultées
Indications approuvées
- Traitement combiné du VIH-1 résistant chez les patients très prétraités, toujours avec ritonavir et d’autres antirétroviraux.
Contre-indications
Absolues
- Child-Pugh B ou C ; hypersensibilite ; rifampicine, millepertuis, sildenafil pour hypertension arterielle pulmonaire, substrats du CYP3A a marge thérapeutique étroite, metoprolol en insuffisance cardiaque et colchicine en insuffisance rénale ou hépatique.
Mises en garde cliniques
- Avertissement encadré : il peut provoquer hépatite clinique, décompensation hépatique et décès. Surveiller et arrêter en cas de lésion. — DailyMed, set_id 08982e49-d2eb-4b25-b01a-1be52fd669ef
- Avertissement encadré : des hémorragies intracrâniennes mortelles et non mortelles ont été rapportées. Évaluer le risque hémorragique et éviter des doses supplémentaires de vitamine E. — DailyMed, set_id 08982e49-d2eb-4b25-b01a-1be52fd669ef
Interactions médicamenteuses
- SévèreSubstrats, inhibiteurs ou inducteurs du CYP3A et de la P-gp
Mécanisme: Tipranavir/ritonavir provoque des interactions complexes et potentiellement mortelles.
Recommandation: Effectuer une conciliation complète ; éviter les associations contre-indiquées et surveiller celles qui sont permises.
DailyMed, set_id 08982e49-d2eb-4b25-b01a-1be52fd669ef
- SévèreAnticoagulants, antiagrégants et vitamine E
Mécanisme: Ils peuvent augmenter le risque hémorragique.
Recommandation: Évaluer le risque, surveiller les saignements et éviter un apport supplémentaire de vitamine E.
DailyMed, set_id 08982e49-d2eb-4b25-b01a-1be52fd669ef
Effets indésirables
Communs (≥1%)
Diarrhée, nausées, fièvre, vomissements, fatigue et céphalées
Rares mais graves
Insuffisance hépatique, hémorragie intracrânienne, réactions cutanées sévères et pancréatite
Grossesse et allaitement
Utiliser pendant la grossesse uniquement si le benefice justifie le risque. Le tipranavir réduit l’efficacité des contraceptifs oraux : utiliser une autre méthode. Ne pas allaiter en cas de VIH sous traitement.
Bibliographie récente (PubMed)
Dengue, caused by dengue virus (DENV), is now endemic in nearly 100 countries and infection incidence is reported in another 30 countries. Yearly an estimated 400 million cases and 2200 deaths are reported. Effective vaccines against DENV are limited and there has been significant focus on the development of effective antiviral against the disease. The World Health Organization has initiated research programs to prioritize the development and optimization of antiviral agents against several viruses including Flaviviridae. A significant effort has been taken by the researchers to develop effective antivirals against DENV. Several potential small-molecule inhibitors like efavirenz, tipranavir and dasabuvir have been tested against envelope and non-structural proteins of DENV, and are in clinical trials around the world. We recently developed one small molecule, namely 7D, targeting the host PF4-CXCR3 axis. 7D inhibited all 4 serotypes of DENV in vitro and specifically DENV2 infection in two different mice models. Although the development of dengue vaccines remains a high priority, antibody cross reactivity among the serotypes and resulting antibody-dependent enhancement (ADE) of infection are major concerns that have limited the development of effective vaccine against DENV. Therefore, there has been a significant emphasis on the development of antiviral drugs against dengue. This review article describes the rescue effects of some of the small molecule inhibitors to viral/host factors associated with DENV pathogenesis. The antivirals are a large and diverse group of agents that are typically classified by the virus infections for which they are used, their chemical structure and their mode of action. Most antiviral agents have been developed in the last 20 to 25 years, many as a result of the major research efforts to develop therapies and means of prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Some of th
The serine protease 23 (PRSS23) is a highly conserved member of trypsin-like serine proteases, which are associated with numerous essential processes, including digestion, blood coagulation, fibrinolysis, development, fertilization, apoptosis, and immunity. Original reports on PRSS23 unfolded not earlier than 2006 when a molecular biology study characterized and described PRSS23 as an ovarian protease. Then, in 2012, another important study was published linking PRSS23 with proliferation of breast cancer cells by an estrogen receptor 1 (ESR1)-dependent transcriptional activation of the serine protease. Thereafter, a developmental study in zebrafish reported the implication of PRSS23 in endothelial-to-mesenchymal transition (EndMT) during cardiac valve formation. Although these early studies on PRSS23 have revealed its involvement in some critical or fundamental processes, only in recent years an increasing number of studies have evolved describing the expression and functions of PRSS23 in various normal physiological conditions, diseases, and experimental configurations. Besides breast cancer, PRSS23 has been shown to be involved in different types of malignancies, e.g., in gastric cancer, where drug screening found that the protease inhibitor tipranavir impedes cancer-promoting PRSS23 expression. New innovative techniques such as single cell RNA-sequencing (scRNA-seq) and bioinformatics studies accelerated the discovery of gene expression changes in smaller cell populations, which, e.g., led to the identification of marked PRSS23 expression in a myofibroblast-like subpopulation in localized scleroderma. This review compiles major and significant research results that have contributed to our current knowledge of PRSS23 and briefly discusses where prospective studies could add to our understanding of this versatile serine protease.
Advances in antiretroviral therapy led to an increase in life expectancy among people living with human immunodeficiency virus (HIV). As aging is characterized by several physiological changes that can influence pharmacokinetics (PK), this systematic review aims to describe the impact of aging on the PK of antiretrovirals (ARV) approved by the Food and Drug Administration (FDA) before 2005. Searches were performed in BVS, EMBASE, and PubMed databases for publications until June 2024. Peer-reviewed published studies were included if they met the following criteria: adults (≥ 18 years) living with HIV; reporting at least one PK parameter or plasma concentration of any ARV approved by the US FDA before 2005 and still used in the clinic: lamivudine (3TC), emtricitabine (FTC), tenofovir disoproxil fumarate (TDF), abacavir (ABC), zidovudine (ZDV), efavirenz (EFV), nevirapine (NVP), atazanavir (ATV), lopinavir (LPV), ritonavir (RTV), tipranavir (TPV), and fosamprenavir (FPV); PK parameters stratified per age group as young (aged 18-49 years) or older (age ≥ 50 years) adults; and manuscripts published in English, Portuguese, or Spanish. All studies were evaluated for risk of bias. The review protocol was registered in the PROSPERO database (registration no. CRD42023463092). Among 106 studies included, only 22 evaluated the PK of participants aged 50 years or older and only 5 studies compared the PK between young and older adults for ATV, RTV, EFV, and 3TC. Our analysis revealed an increase in minimal concentration (Cmin) values for LPV, RTV, and ATV in older adults. While increased values of the area under the curve (AUC) and maximum concentration (Cmax) were observed in older adults using ATV, 3TC, and FTC, no differences in PK were apparent between young and older adults for ABC and EFV, with no estimation possible for ZDV. Exposure to 3TC, TDF, FTC, ATV, LPV, and RTV increases with age, while exposure to ABC and EFV appears to be unaffected. Despite the large quantity of