Fenofibrate
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Complemento de dieta y otras medidas para hipertrigliceridemia grave, hiperlipidemia mixta cuando las estatinas no se toleran o están contraindicadas, o junto con estatina en pacientes de alto riesgo con triglicéridos y C-HDL no controlados.
Contraindicaciones
Absolutas
- Hipersensibilidad al fenofibrato o los excipientes, incluida alergia a cacahuete, soja o productos relacionados.
- Insuficiencia hepática, enfermedad conocida de vesícula o insuficiencia renal grave con TFGe <30.
- Pancreatitis aguda o crónica, salvo pancreatitis aguda por hipertrigliceridemia grave.
- Fotosensibilidad o fototoxicidad previa con fibratos o ketoprofeno.
Advertencias clínicas
- Advertencia mayor · Controlar transaminasas cada 3 meses durante los primeros 12 meses y después periódicamente; suspender si AST o ALT superan 3 veces el límite normal o se confirma hepatitis. — https://cima.aemps.es/cima/dochtml/ft/88287/FT_88287.html
- Advertencia mayor · Puede causar toxicidad muscular y rabdomiólisis, sobre todo con insuficiencia renal, hipoalbuminemia, hipotiroidismo, edad avanzada, alcohol o combinación con estatinas/fibratos. Suspender ante síntomas y CPK >5 veces el valor normal. — https://cima.aemps.es/cima/dochtml/ft/88287/FT_88287.html
- Advertencia mayor · Puede producir pancreatitis y aumentos reversibles de creatinina; vigilar función renal y suspender si la creatinina supera en 50 % el límite superior normal. — https://cima.aemps.es/cima/dochtml/ft/88287/FT_88287.html
Interacciones medicamentosas
- ModeradaAnticoagulantes orales
Mecanismo: Fenofibrato potencia su efecto y aumenta el riesgo de hemorragia.
Recomendación: Reducir inicialmente la dosis del anticoagulante en un tercio y ajustar según INR.
https://cima.aemps.es/cima/dochtml/ft/88287/FT_88287.html
- ModeradaEstatinas u otros fibratos
Mecanismo: Aumentan el riesgo de toxicidad muscular grave.
Recomendación: Reservar la combinación para dislipidemia grave de alto riesgo y vigilar estrechamente síntomas musculares.
https://cima.aemps.es/cima/dochtml/ft/88287/FT_88287.html
- ModeradaCiclosporina
Mecanismo: Se ha comunicado deterioro renal grave reversible.
Recomendación: Vigilar estrechamente la función renal y suspender fenofibrato ante alteración grave.
https://cima.aemps.es/cima/dochtml/ft/88287/FT_88287.html
Eventos adversos
Comunes (≥1%)
Dolor abdominal · Náuseas · Vómitos · Diarrea · Flatulencia · Aumento de transaminasas · Aumento de homocisteína
Raros pero graves
Rabdomiólisis · Pancreatitis · Tromboembolismo venoso · Hepatitis o reacción cutánea grave
Embarazo y lactancia
Durante el embarazo, usar solo tras una valoración cuidadosa del beneficio y el riesgo. No usar durante la lactancia.
Bibliografía reciente (PubMed)
Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.
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.
Findings from cardiovascular outcome trials suggest that fenofibrate therapy may reduce the progression of diabetic retinopathy. We recruited and followed adults with nonreferable diabetic retinopathy or maculopathy using the national Diabetic Eye Screening (DES) program in Scotland. We randomly assigned participants to receive 145-mg fenofibrate tablets or placebo (taken daily or, in those with impaired renal function, on alternate days). The primary outcome was a composite of developing referable diabetic retinopathy or maculopathy (based on Scotland's DES grading scheme) or treatment (intravitreal injection, retinal laser, vitrectomy) for retinopathy or maculopathy. A total of 1151 participants were randomly assigned to treatment. During a median of 4.0 years, progression to referable diabetic retinopathy or maculopathy, or treatment thereof, occurred in 131 (22.7%) of 576 participants in the fenofibrate group and 168 (29.2%) of 575 in the placebo group (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.91; P=0.006). In the fenofibrate group compared with the placebo group, the frequencies for any progression of retinopathy or maculopathy were 185 (32.1%) vs. 231 (40.2%); hazard ratio, 0.74; 95% CI, 0.61 to 0.90 and for the development of macular edema were 22 (3.8%) vs. 43 (7.5%); hazard ratio, 0.50; 95% CI, 0.30 to 0.84. Seventeen (3.0%) participants assigned fenofibrate and 28 (4.9%) assigned placebo were given treatment for retinopathy (hazard ratio, 0.58; 95% CI, 0.31 to 1.06). There was no effect on visual function, quality of life, or visual acuity. Trial-averaged estimated glomerular filtration rate was 7.9 (95% CI, 6.8 to 9.1) ml/min/1.73 m2 lower in participants in the fenofibrate group compared with the placebo group. Serious adverse events occurred in 208 (36.1%) participants allocated fenofibrate and 204 (35.5%) participants allocated placebo. Fenofibrate reduced progression of diabetic retinopathy compared with placebo among participants w
Despite treatment with statins, patients with elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides remain at increased risk for adverse cardiovascular events. Consequently, novel pharmaceutical drugs have been developed to control and modify the composition of blood lipids to ultimately prevent fatal cardiovascular events in patients with dyslipidaemia. This article reviews established and emerging lipid-lowering drugs regarding their mechanism of action, development stage, ongoing clinical trials, side effects, effect on blood lipids and reduction in cardiovascular morbidity and mortality. We conducted a keyword search to identify studies on established and emerging lipid modifying drugs. Results were summarized in a narrative overview. Established pharmaceutical treatment options include the Niemann-Pick-C1 like-1 protein (NPC1L1) inhibitor ezetimibe, the protein convertase subtilisin-kexin type 9 (PCSK9) inhibitors alirocumab and evolocumab, fibrates as peroxisome proliferator receptor alpha (PPAR-α) activators, and the omega-3 fatty acid icosapent ethyl. Statins are recommended as the first-line therapy for primary and secondary cardiovascular prevention in patients with hypercholesterinaemia and hypertriglyceridemia. For secondary prevention in hypercholesterinaemia, second-line options such as statin add-on or statin-intolerant treatments are ezetimibe, alirocumab and evolocumab. For secondary prevention in hypertriglyceridemia, second-line options such as statin add-on or statin-intolerant treatments are icosapent ethyl and fenofibrate. Robust data for these add-on therapeutics in primary cardiovascular prevention remains scarce. Recent biotechnological advances have led to the development of innovative small molecules (bempedoic acid, lomitapide, pemafibrate, docosapentaenoic and eicosapentaenoic acid), antibodies (evinacumab), antisense oligonucleotides (mipomersen, volanesorsen, pelcarsen, olezarsen), small interfering RNA (inclisiran, ol