Gemfibrozil
Sources réglementaires consultées
Indications approuvées
- Complément au régime et aux mesures non médicamenteuses dans l'hypertriglycéridémie sévère, l'hyperlipidémie mixte ou l'hypercholestérolémie primaire lorsque les statines sont contre-indiquées ou mal tolérées ; également prévention primaire chez certains hommes à haut risque.
Contre-indications
Absolues
- Hypersensibilité au gemfibrozil ou aux excipients.
- Dysfonction hépatique ou insuffisance rénale sévère.
- Maladie de la vésicule ou des voies biliaires, y compris calculs.
- Utilisation avec le répaglinide, le dasabuvir, le sélexipag, la simvastatine ou la rosuvastatine 40 mg.
- Antécédent de réaction photoallergique ou phototoxique lors d’un traitement par fibrates.
Mises en garde cliniques
- Mise en garde majeure · Une myopathie et une rhabdomyolyse peuvent survenir. Arrêter en cas de myalgies diffuses, faiblesse ou CPK >5 fois la limite normale ; le risque augmente avec les statines et les facteurs prédisposants. — https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- Mise en garde majeure · Il peut augmenter le cholestérol biliaire et favoriser les calculs ; examiner la vésicule et arrêter si des calculs sont détectés. — https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- Mise en garde majeure · Surveiller périodiquement les lipides, la fonction hépatique et l'hémogramme ; arrêter si la réponse est insuffisante après 3 mois ou si les anomalies hépatiques persistent. — https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
Interactions médicamenteuses
- ModéréeRépaglinide, dasabuvir ou sélexipag
Mécanisme: L'inhibition puissante du CYP2C8 et des transporteurs augmente fortement leur exposition et leur toxicité.
Recommandation: Ne pas associer.
https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- ModéréeStatines
Mécanisme: Elles augmentent le risque de myopathie et de rhabdomyolyse.
Recommandation: Éviter ; la simvastatine et la rosuvastatine 40 mg sont contre-indiquées.
https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- SévèreEnzalutamide
Mécanisme: L’association peut augmenter l’exposition à l’enzalutamide et le risque de convulsions.
Recommandation: Éviter ; si l’association est inévitable, réduire la dose d’enzalutamide selon son RCP et surveiller la toxicité.
https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
- SévèreSubstrats du CYP2C9 ou du CYP2C8, dont la warfarine et le glimépiride
Mécanisme: Le gemfibrozil inhibe le CYP2C8 et le CYP2C9 et peut augmenter l’exposition à leurs substrats, avec risque de saignement ou d’hypoglycémie.
Recommandation: Avec la warfarine, surveiller étroitement l’INR et ajuster ; avec le glimépiride, surveiller la glycémie et l’hypoglycémie.
https://cima.aemps.es/cima/dochtml/ft/61830/FT_61830.html
Effets indésirables
Communs (≥1%)
Dyspepsie · Diarrhée · Vomissements · Nausées · Douleur abdominale · Constipation · Flatulences · Vertiges ou céphalées · Eczéma ou éruption · Fatigue
Rares mais graves
Rhabdomyolyse ou myopathie · Pancréatite · Insuffisance médullaire ou cytopénies sévères · Angio-œdème ou œdème laryngé
Grossesse et allaitement
Ne pas utiliser pendant la grossesse sauf nécessité claire. Ne pas utiliser pendant l'allaitement.
Bibliographie récente (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