Lovastatin
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Complemento de la dieta para reducir colesterol total y C-LDL en hipercolesterolemia primaria cuando las medidas no farmacológicas son insuficientes, y para reducir riesgo coronario o ralentizar la aterosclerosis coronaria en pacientes seleccionados.
Contraindicaciones
Absolutas
- Hipersensibilidad a cualquiera de los componentes.
- Enfermedad hepática activa o elevación persistente no explicada de transaminasas.
- Uso concomitante de inhibidores potentes de CYP3A4.
- Embarazo o lactancia.
Advertencias clínicas
- Advertencia mayor · Puede causar miopatía y rabdomiólisis, a veces con insuficiencia renal aguda o muerte. Suspender si se diagnostica o sospecha miopatía, si la CK aumenta marcadamente o ante dolor, sensibilidad o debilidad muscular inexplicados. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- Advertencia mayor · Obtener enzimas hepáticas antes de iniciar y repetir según la situación clínica; interrumpir ante lesión hepática grave con síntomas, hiperbilirrubinemia o ictericia. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
Interacciones medicamentosas
- ModeradaInhibidores potentes de CYP3A4
Mecanismo: Aumentan la exposición a lovastatina y el riesgo de miopatía o rabdomiólisis.
Recomendación: No combinar; suspender lovastatina durante un tratamiento breve inevitable.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SeveraGemfibrozilo, otros fibratos o niacina ≥1 g/día
Mecanismo: Aumentan el riesgo de miopatía y rabdomiólisis.
Recomendación: Evitar gemfibrozilo y valorar estrictamente otras combinaciones.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SeveraDiltiazem, dronedarona, verapamilo o danazol
Mecanismo: Aumentan el riesgo muscular con lovastatina.
Recomendación: Iniciar con 10 mg y no superar 20 mg/día.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SeveraCiclosporina
Mecanismo: Aumenta la exposición a lovastatina y el riesgo de miopatía o rabdomiólisis.
Recomendación: Evitar la combinación.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SeveraAmiodaronaC01BD01
Mecanismo: Aumenta el riesgo de miopatía y rabdomiólisis asociado a lovastatina.
Recomendación: No superar 40 mg/día de lovastatina.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SeveraPomelo o zumo de pomelo
Mecanismo: Puede elevar las concentraciones de lovastatina mediante inhibición de CYP3A4.
Recomendación: Evitar el pomelo durante el tratamiento.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- ModeradaAnticoagulantes cumarínicos
Mecanismo: Lovastatina puede aumentar el tiempo de protrombina y el INR.
Recomendación: Controlar TP/INR antes de iniciar y durante los ajustes hasta estabilización.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SeveraColchicina o ranolazina
Mecanismo: Se han descrito casos de miopatía y rabdomiólisis con la combinación.
Recomendación: Con ranolazina, considerar ajustar la dosis de lovastatina. Con cualquiera de las dos combinaciones, valorar el beneficio, vigilar síntomas musculares y suspender ante sospecha de miopatía.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
Eventos adversos
Comunes (≥1%)
Flatulencia · Cefalea · Mialgia · Dolor abdominal · Estreñimiento · Diarrea · Náuseas
Raros pero graves
Rabdomiólisis o miopatía necrotizante inmunomediada · Insuficiencia hepática grave · Anafilaxia, angioedema o reacción cutánea grave
Embarazo y lactancia
Categoría FDA: X
Contraindicada durante el embarazo; suspender inmediatamente si se reconoce un embarazo. No amamantar durante el tratamiento por el riesgo de reacciones graves en el lactante.
Bibliografía reciente (PubMed)
While behavioral interventions remain the mainstay of treatment of autism spectrum disorder (ASD), several potential targeted treatments addressing the underlying neurophysiology of ASD have emerged in the last few years. These are promising for the potential to, in future, become part of the mainstay treatment in addressing the core symptoms of ASD. Although it is likely that the development of future targeted treatments will be influenced by the underlying heterogeneity in etiology, associated genetic mechanisms influencing ASD are likely to be the first targets of treatments and even gene therapy in the future for ASD. In this article, we provide a review of current psychopharmacological treatment in ASD including those used to address common comorbidities of the condition and upcoming new targeted approaches in autism management. Medications including metformin, arbaclofen, cannabidiol, oxytocin, bumetanide, lovastatin, trofinetide, and dietary supplements including sulforophane and N-acetylcysteine are discussed. Commonly used medications to address the comorbidities associated with ASD including atypical antipsychotics, serotoninergic agents, alpha-2 agonists, and stimulant medications are also reviewed. Targeted treatments in Fragile X syndrome (FXS), the most common genetic disorder leading to ASD, provide a model for new treatments that may be helpful for other forms of ASD. No relevant published information exists on the use of lovastatin during breastfeeding. Because of a concern with disruption of infant lipid metabolism, the consensus is that lovastatin should not be used during breastfeeding. However, others have argued that children homozygous for familial hypercholesterolemia are treated with statins beginning at 1 year of age, that statins have low oral bioavailability, and risks to the breastfed infant are low, especially with rosuvastatin and pravastatin.[1] Until more data become available, an alternate drug may be preferred, especially while nur
Since the 2010 classification of ichthyoses, our understanding of hereditary epidermal differentiation disorders (EDDs) has markedly increased, allowing for consideration of new therapeutic targets based on disease pathogenesis. A new gene- and protein product function-based classification focuses on shared mechanisms of disease pathogenesis, with the possibility that grouped disorders may respond similarly to new therapeutics. These EDDs have been subdivided into syndromic (sEDD), nonsyndromic with features limited to skin and appendages, and predominantly palmoplantar skin involvement (nonsyndromic and syndromic). sEDDs have clinically important extracutaneous features related to the gene alteration. Often, recognition based on skin manifestations facilitates early gene-based diagnosis, discussion of prognosis, genetic counselling and the initiation of therapy. All sEDDs are rare; the most common are STS-sEDD (formerly known as X-linked ichthyosis) and SPINK5-sEDD (formerly known as Netherton syndrome). Given the rarity, frequent association with early demise and variable clinical features of sEDDs, the natural history of the diseases with advancing age and genotype-phenotype relationships are poorly defined. Of the 51 sEDDs, associated neurological (n = 36; 71%) and/or ophthalmological (n = 25; 49%) findings are most common, and 39% (n = 20) have associated hair abnormalities. The widespread use of topical lovastatin for cholesterol synthesis-related sEDDs represents the prototype of pathogenesis-based therapy. This concept of upstream inhibition to prevent metabolite accumulation and supplementation with the pathway end product potentially applies to other sEDDs, such as those affecting ceramide synthesis and transport. Topical or systemically administered inhibition of activated pathways is another potential approach, exemplified by the emerging treatment of SPINK5-sEDD with kallikrein inhibitors. Many sEDDs may be amenable to gene editing or the introduction o
Statins reduce cholesterol, prevent cardiovascular disease, and are among the most commonly prescribed medications in the world. Statin-associated musculoskeletal symptoms (SAMS) impact statin adherence and ultimately can impede the long-term effectiveness of statin therapy. There are several identified pharmacogenetic variants that impact statin disposition and adverse events during statin therapy. SLCO1B1 encodes a transporter (SLCO1B1; alternative names include OATP1B1 or OATP-C) that facilitates the hepatic uptake of all statins. ABCG2 encodes an efflux transporter (BCRP) that modulates the absorption and disposition of rosuvastatin. CYP2C9 encodes a phase I drug metabolizing enzyme responsible for the oxidation of some statins. Genetic variation in each of these genes alters systemic exposure to statins (i.e., simvastatin, rosuvastatin, pravastatin, pitavastatin, atorvastatin, fluvastatin, lovastatin), which can increase the risk for SAMS. We summarize the literature supporting these associations and provide therapeutic recommendations for statins based on SLCO1B1, ABCG2, and CYP2C9 genotype with the goal of improving the overall safety, adherence, and effectiveness of statin therapy. This document replaces the 2012 and 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for SLCO1B1 and simvastatin-induced myopathy. Lovastatin is a commonly used cholesterol lowering agent (statin) that is associated with mild, asymptomatic and self-limited serum aminotransferase elevations during therapy and rarely with clinically apparent acute liver injury.