Gemfibrozil
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Complemento de dieta y medidas no farmacológicas para hipertrigliceridemia grave, hiperlipidemia mixta o hipercolesterolemia primaria cuando las estatinas están contraindicadas o no se toleran; también prevención primaria en hombres seleccionados de alto riesgo.
Contraindicaciones
Absolutas
- Hipersensibilidad al gemfibrozilo o a los excipientes.
- Disfunción hepática o renal grave.
- Enfermedad de vesícula o vías biliares, incluidos cálculos.
- Uso con repaglinida, dasabuvir, selexipag, simvastatina o rosuvastatina 40 mg.
- Antecedente de reacción fotoalérgica o fototóxica durante tratamiento con fibratos.
Advertencias clínicas
- Advertencia mayor · Puede causar miopatía y rabdomiólisis. Suspender ante mialgia difusa, debilidad o CPK >5 veces el límite normal; el riesgo aumenta con estatinas y factores predisponentes. — https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- Advertencia mayor · Puede aumentar el colesterol biliar y favorecer colelitiasis; estudiar la vesícula y suspender si se detectan cálculos. — https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- Advertencia mayor · Controlar periódicamente lípidos, función hepática y hemograma; suspender si la respuesta es insuficiente a los 3 meses o persisten anomalías hepáticas. — https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
Interacciones medicamentosas
- ModeradaRepaglinida, dasabuvir o selexipag
Mecanismo: La inhibición potente de CYP2C8 y transportadores aumenta mucho su exposición y toxicidad.
Recomendación: No combinar.
https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- ModeradaEstatinas
Mecanismo: Aumentan el riesgo de miopatía y rabdomiólisis.
Recomendación: Evitar; simvastatina y rosuvastatina 40 mg están contraindicadas.
https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- SeveraEnzalutamida
Mecanismo: La combinación puede aumentar la exposición a enzalutamida y el riesgo de convulsiones.
Recomendación: Evitar; si es inevitable, reducir la dosis de enzalutamida según su ficha técnica y vigilar toxicidad.
https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- SeveraSustratos de CYP2C9 o CYP2C8, incluidos warfarina y glimepirida
Mecanismo: Gemfibrozilo inhibe CYP2C8 y CYP2C9 y puede aumentar la exposición a sus sustratos, con hemorragia o hipoglucemia.
Recomendación: Con warfarina, vigilar estrechamente INR y ajustar; con glimepirida, vigilar glucemia e hipoglucemia.
https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
Eventos adversos
Comunes (≥1%)
Dispepsia · Diarrea · Vómitos · Náuseas · Dolor abdominal · Estreñimiento · Flatulencia · Vértigo o cefalea · Eccema o erupción · Fatiga
Raros pero graves
Rabdomiólisis o miopatía · Pancreatitis · Insuficiencia medular o citopenias graves · Angioedema o edema laríngeo
Embarazo y lactancia
No usar durante el embarazo salvo necesidad clara. No usar durante la lactancia.
Bibliografía reciente (PubMed)
Hypertriglyceridemia therapy is essential for preventing cardiovascular diseases. Fibrates belong to an important class of lipid-lowering drugs useful for the management of dyslipidaemia. By acting on the peroxisome proliferator-activated receptor (PPAR)-α, these drugs lower serum triglyceride levels and raise high-density lipoprotein cholesterol. Fibrate monotherapy is associated with a risk of myopathy and this risk is enhanced when these agents are administered together with statins. However, whereas gemfibrozil can increase plasma concentrations of statins, fenofibrate has less influence on the pharmacokinetics of statins. Pemafibrate is a new PPAR-α-selective drug considered for therapy, and clinical trials are ongoing. Apart from this class of drugs, new therapies have emerged with different mechanisms of action to reduce triglycerides and the risk of cardiovascular diseases. No relevant published information exists on the use of gemfibrozil during breastfeeding. Because of a concern with disruption of infant lipid metabolism, gemfibrozil is best avoided during breastfeeding. An alternate drug is preferred, especially while nursing a newborn or preterm infant.
Atherogenic dyslipidemia is an important risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes, obesity, and metabolic disorders. Statin therapy, the standard treatment for dyslipidemia management, falls short of controlling the residual risk of adverse cardiovascular events, even with good control of low-density lipoprotein cholesterol (LDL-C). Apolipoprotein B (apoB), in addition to non-high-density lipoprotein cholesterol (non-HDL-C), is considered a better measure of residual risk and a more comprehensive treatment target in atherogenic dyslipidemia. Fibrates in combination with statins represent a proven therapeutic modality for atherogenic dyslipidemia. Fibrates lower triglyceride-rich lipoproteins (TRL), TRL remnants, and small dense LDL particles while increasing HDL-C levels. However, only fenofibrate appears to reduce apoB, whereas gemfibrozil and pemafibrate do not. This leads to a reduction in atherogenic lipids, as measured by a significant decrease in apoB/non-HDL-C levels, and a corresponding reduction in CVD risk. Real-world efficacy studies and CVD outcome trials have shown that fenofibrate may be an option in combination with statins compared to other fibrates and is well tolerated. Additionally, evidence from real-world studies of the fenofibrate-statin combination in patients over a period of up to 20 years has dispelled safety concerns regarding long-term use of fenofibrate.
There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB. A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also info