Lovastatin
Sources réglementaires consultées
Indications approuvées
- Complément au régime pour réduire le cholestérol total et le LDL-C dans l'hypercholestérolémie primaire lorsque les mesures non médicamenteuses sont insuffisantes, et pour réduire le risque coronarien ou ralentir l'athérosclérose coronaire chez certains patients.
Contre-indications
Absolues
- Hypersensibilité à l'un des composants.
- Maladie hépatique active ou élévation persistante inexpliquée des transaminases.
- Utilisation concomitante d'inhibiteurs puissants du CYP3A4.
- Grossesse ou allaitement.
Mises en garde cliniques
- Mise en garde majeure · Une myopathie et une rhabdomyolyse peuvent survenir, parfois avec insuffisance rénale aiguë ou décès. Arrêter en cas de myopathie diagnostiquée ou suspectée, d'élévation marquée de la CK ou de douleur, sensibilité ou faiblesse musculaire inexpliquée. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- Mise en garde majeure · Contrôler les enzymes hépatiques avant l'instauration puis selon la situation clinique ; interrompre en cas de lésion hépatique grave avec symptômes, hyperbilirubinémie ou ictère. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
Interactions médicamenteuses
- ModéréeInhibiteurs puissants du CYP3A4
Mécanisme: Ils augmentent l'exposition à la lovastatine et le risque de myopathie ou de rhabdomyolyse.
Recommandation: Ne pas associer ; suspendre la lovastatine pendant un traitement bref inévitable.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SévèreGemfibrozil, autres fibrates ou niacine ≥1 g/jour
Mécanisme: Ils augmentent le risque de myopathie et de rhabdomyolyse.
Recommandation: Éviter le gemfibrozil et évaluer strictement les autres associations.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SévèreDiltiazem, dronédarone, vérapamil ou danazol
Mécanisme: Ils augmentent le risque de toxicité musculaire avec la lovastatine.
Recommandation: Commencer à 10 mg et ne pas dépasser 20 mg/jour.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SévèreCiclosporine
Mécanisme: Elle augmente l’exposition à la lovastatine et le risque de myopathie ou de rhabdomyolyse.
Recommandation: Éviter l’association.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SévèreAmiodaroneC01BD01
Mécanisme: Elle augmente le risque de myopathie et de rhabdomyolyse associé à la lovastatine.
Recommandation: Ne pas dépasser 40 mg/jour de lovastatine.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SévèrePamplemousse ou jus de pamplemousse
Mécanisme: Il peut augmenter les concentrations de lovastatine par inhibition du CYP3A4.
Recommandation: Éviter le pamplemousse pendant le traitement.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- ModéréeAnticoagulants coumariniques
Mécanisme: La lovastatine peut augmenter le temps de prothrombine et l’INR.
Recommandation: Contrôler le TP/INR avant l’instauration et pendant les ajustements jusqu’à stabilisation.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- SévèreColchicine ou ranolazine
Mécanisme: Des cas de myopathie et de rhabdomyolyse ont été rapportés avec l’association.
Recommandation: Avec la ranolazine, envisager d'adapter la dose de lovastatine. Avec l'une ou l'autre association, évaluer le bénéfice, surveiller les symptômes musculaires et arrêter en cas de suspicion de myopathie.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
Effets indésirables
Communs (≥1%)
Flatulences · Céphalées · Myalgie · Douleur abdominale · Constipation · Diarrhée · Nausées
Rares mais graves
Rhabdomyolyse ou myopathie nécrosante à médiation immunitaire · Insuffisance hépatique sévère · Anaphylaxie, angio-œdème ou réaction cutanée sévère
Grossesse et allaitement
Catégorie FDA: X
Contre-indiquée pendant la grossesse ; arrêter immédiatement si une grossesse est constatée. Ne pas allaiter pendant le traitement en raison du risque de réactions graves chez le nourrisson.
Bibliographie récente (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.