Bezafibrate
Sources réglementaires consultées
Indications approuvées
- Complément au régime et aux autres mesures dans l'hypertriglycéridémie sévère, avec ou sans HDL-C bas, ou l'hyperlipidémie mixte lorsque les statines sont contre-indiquées ou mal tolérées.
Contre-indications
Absolues
- Hypersensibilité au bézafibrate, aux autres fibrates ou aux excipients.
- Maladie hépatique, trouble de la vésicule biliaire ou cholélithiase.
- Clairance de la créatinine <60 ml/min, dialyse ou syndrome néphrotique.
- Grossesse ou allaitement.
- Utilisation avec le maléate de perhexiline ou des inhibiteurs de la MAO.
- Antécédent de réaction photoallergique ou phototoxique lors d’un traitement par fibrates.
- Association avec une statine chez les patients présentant des facteurs prédisposant à une myopathie.
Mises en garde cliniques
- Mise en garde majeure · Une myopathie et une rhabdomyolyse peuvent survenir, surtout en cas d'insuffisance rénale, d'hypoalbuminémie ou avec des statines. Arrêter en cas de symptômes musculaires avec CPK >5 fois la normale ou de suspicion de rhabdomyolyse. — https://cima.aemps.es/cima/dochtml/ft/57150/FT_57150.html
- Mise en garde majeure · Des calculs biliaires peuvent survenir ; effectuer une évaluation appropriée en cas de signes ou symptômes évocateurs. — https://cima.aemps.es/cima/dochtml/ft/57150/FT_57150.html
Interactions médicamenteuses
- ModéréeAnticoagulants coumariniques
Mécanisme: Le bézafibrate renforce leur effet anticoagulant.
Recommandation: Réduire la dose de l'anticoagulant de 30 à 50 % à l'instauration et l'ajuster selon la coagulation.
https://cima.aemps.es/cima/dochtml/ft/57150/FT_57150.html
- ModéréeStatines
Mécanisme: Elles augmentent le risque de myopathie et de rhabdomyolyse.
Recommandation: Éviter sauf cas exceptionnels strictement indiqués sans facteurs prédisposants ; surveiller étroitement.
https://cima.aemps.es/cima/dochtml/ft/57150/FT_57150.html
- ModéréeRésines échangeuses d'ions
Mécanisme: Elles réduisent l'absorption du bézafibrate.
Recommandation: Espacer les prises d'au moins 2 heures.
https://cima.aemps.es/cima/dochtml/ft/57150/FT_57150.html
- ModéréeSulfamides hypoglycémiants ou insuline
Mécanisme: Le bézafibrate peut renforcer l’effet hypoglycémiant.
Recommandation: Surveiller la glycémie et ajuster le traitement antidiabétique si nécessaire.
https://cima.aemps.es/cima/dochtml/ft/57150/FT_57150.html
- SévèreColchicine
Mécanisme: L’association peut augmenter le risque de myopathie.
Recommandation: Utiliser avec prudence et surveiller les symptômes musculaires et la CPK si nécessaire.
https://cima.aemps.es/cima/dochtml/ft/57150/FT_57150.html
- SévèreImmunosuppresseurs chez les patients transplantés
Mécanisme: Une altération rénale importante et réversible a été rapportée lors de l’utilisation concomitante.
Recommandation: Surveiller étroitement la fonction rénale et arrêter le bézafibrate en cas de modification pertinente.
https://cima.aemps.es/cima/dochtml/ft/57150/FT_57150.html
Effets indésirables
Communs (≥1%)
Diminution de l'appétit · Troubles gastro-intestinaux
Rares mais graves
Rhabdomyolyse · Agranulocytose ou pancytopénie · Syndrome de Stevens-Johnson ou nécrolyse épidermique toxique
Grossesse et allaitement
Contre-indiqué pendant la grossesse et l'allaitement.
Bibliographie récente (PubMed)
Primary biliary cholangitis (PBC) is an archetypal autoimmune disease. Chronic lymphocytic cholangitis is associated with interface hepatitis, ductopenia, cholestasis, and progressive biliary fibrosis. People living with PBC are frequently symptomatic, experiencing a quality-of-life burden dominated by fatigue, itch, abdominal pain, and sicca complex. Although the female predominance, specific serum autoantibodies, immune-mediated cellular injury, as well as genetic (HLA and non-HLA) risk factors, identify PBC as autoimmune, to date treatment has focused on cholestatic consequences. Biliary epithelial homeostasis is abnormal and contributes to disease. The impact of cholangiocyte senescence, apoptosis, and impaired bicarbonate secretion enhances chronic inflammation and bile acid retention. First-line therapy is a non-specific anti-cholestatic agent, ursodeoxycholic acid. For those with residual cholestasis biochemically, obeticholic acid is introduced, and this semisynthetic farnesoid X receptor agonist adds choleretic, anti-fibrotic, and anti-inflammatory activity. Future PBC licensed therapy will likely include peroxisome proliferator activated receptor (PPAR) pathway agonists, including specific PPAR-delta agonism (seladelpar), as well as elafibrinor and saroglitazar (both with broader PPAR agonism). These agents dovetail the clinical and trial experience for off-label bezafibrate and fenofibrate use. Symptom management is essential, and encouragingly, PPAR agonists reduce itch; IBAT inhibition (eg, linerixibat) also appears promising for pruritus. For those where liver fibrosis is the target, NOX inhibition is being evaluated. Earlier stage therapies in development include therapy to impact immunoregulation in patients, as well other approaches to treating pruritus (eg, antagonists of MrgprX4). Collectively the PBC therapeutic landscape is exciting. Therapy goals are increasingly proactive and individualized and aspire to rapidly achieve normal serum tests and
Primary biliary cholangitis (PBC) is an enigmatic, autoimmune disease targeting the small intralobular bile ducts resulting in cholestasis and potentially progression to biliary cirrhosis. Primarily affecting middle-aged women, the diagnosis of PBC is typically straightforward, with most patients presenting with cholestatic liver tests and the highly specific antimitochondrial antibody. For decades, the foundational treatment of PBC has been ursodeoxycholic acid, which delays disease progression in most patients but has no impact on PBC symptoms. Large cohort studies of patients with PBC have established the benefit of maximizing the reduction in serum alkaline phosphatase levels with ursodeoxycholic acid and the need to add second-line agents in patients who do not achieve an adequate response. Advances in the understanding of bile acid physiology have led to the development of new agents that improve cholestasis in patients with PBC and are predicted to reduce the risk of disease progression. Obeticholic acid, the first second-line therapy to be approved for PBC, significantly improves liver biochemistries and has been associated with improved long-term clinical outcomes but is limited by its propensity to induce pruritus. Elafibranor and seladelpar are peroxisome proliferator-activated receptor agonists recently approved for use in patients with PBC, whereas bezafibrate and fenofibrate are available as off-label therapies. They also have shown biochemical improvements among patients with an inadequate response to ursodeoxycholic acid but may improve symptoms of pruritus. Herein, we review the patient features to consider when deciding whether a second-line agent is indicated and which agent to consider for a truly personalized approach to PBC patient care.
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease phenotypes which start with simple steatosis and lipid accumulation in the hepatocytes - a typical histological lesions characteristic. It may progress to non-alcoholic steatohepatitis (NASH) that is characterized by hepatic inflammation and/or fibrosis and subsequent onset of NAFLD-related cirrhosis and hepatocellular carcinoma (HCC). Due to the central role of the liver in metabolism, NAFLD is regarded as a result of and contribution to the metabolic abnormalities seen in the metabolic syndrome. Peroxisome proliferator-activated receptors (PPARs) has three subtypes, which govern the expression of genes responsible for energy metabolism, cellular development, inflammation, and differentiation. The agonists of PPARα, such as fenofibrate and clofibrate, have been used as lipid-lowering drugs in clinical practice. Thiazolidinediones (TZDs) - ligands of PPARγ, such as rosiglitazone and pioglitazone, are also used in the treatment of type 2 diabetes (T2D) with insulin resistance (IR). Increasing evidence suggests that PPARβ/δ agonists have potential therapeutic effects in improving insulin sensitivity and lipid metabolism disorders. In addition, PPARs ligands have been considered as potential therapeutic drugs for hypertension, atherosclerosis (AS) or diabetic nephropathy. Their crucial biological roles dictate the significance of PPARs-targeting in medical research and drug discovery. Here, it reviews the biological activities, ligand selectivity and biological functions of the PPARs family, and discusses the relationship between PPARs and the pathogenesis of NAFLD and metabolic syndrome. This will open new possibilities for PPARs application in medicine, and provide a new idea for the treatment of fatty liver and related diseases.
Pruritus in cholestatic liver diseases can be a major burden and dramatically impair the quality of life of those affected. Here, we provide an update on the latest insights into the molecular pathogenesis of and novel therapeutic approaches for cholestasis-associated itch. Endogenous and exogenous small-molecule pruritogen candidates bind to their receptors on unmyelinated itch C-fibres in the skin. Candidate pruritogens in cholestasis include certain lysophospholipids and sulfated progesterone metabolites, among others, whereas total bile acid or bilirubin conjugates seem unlikely to have a dominant role in the pathogenesis of cholestasis-associated pruritus. Transmission of itch signals via primary, secondary and tertiary itch neurons to the postcentral gyrus and activation of scratch responses offer various targets for therapeutic intervention. At present, evidence-based treatment options for pruritus in fibrosing cholangiopathies, such as primary biliary cholangitis and primary sclerosing cholangitis, are the peroxisome proliferator-associated receptor (PPAR) agonist bezafibrate and the pregnane X receptor (PXR) agonist rifampicin. In pruritus of intrahepatic cholestasis of pregnancy, ursodeoxycholic acid is recommended and might be supported in the third trimester by rifampicin if needed. Alternatively, non-absorbable anion exchange resins, such as cholestyramine, can be administered, albeit with poor trial evidence. Liver transplantation for intolerable refractory pruritus has become an extremely rare therapeutic strategy.
Postprandial hyperlipidemia showing postprandial increases in serum triglyceride (TG) is associated with the development of atherosclerotic cardiovascular disease (ASCVD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed; however, this test is very time-consuming and is difficult to perform. Elevated serum TG levels reflect an increase in TG-rich lipoproteins (TRLs), such as chylomicrons (CM), very low-density lipoproteins (VLDL), and their remnants (CM remnants [CMRs] and VLDL remnants [VLDLRs]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurement of apo B48, which is a constituent of CM and CMR; non-fasting TG, which includes TG content in all lipoproteins including CM and CMR; non-high-density lipoprotein cholesterol (non-HDL-C), which includes TRLs and low-density lipoprotein; and remnant cholesterol are useful to reveal the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an inducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with postprandial hyperlipidemia have various atherogenic properties such as induction of inflammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss, and exercise positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, fenofibrate, bezafibrate, ezetimibe, and eicosapentaenoic acid have been shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and