Lovastatin
Regulatory sources consulted
Approved indications
- Adjunct to diet to reduce total cholesterol and LDL-C in primary hypercholesterolemia when non-drug measures are insufficient, and to reduce coronary risk or slow coronary atherosclerosis in selected patients.
Contraindications
Absolute
- Hypersensitivity to any component.
- Active liver disease or unexplained persistent transaminase elevations.
- Concomitant use of strong CYP3A4 inhibitors.
- Pregnancy or breastfeeding.
Clinical warnings
- Major warning · Myopathy and rhabdomyolysis may occur, sometimes with acute renal failure or death. Discontinue if myopathy is diagnosed or suspected, CK is markedly elevated, or unexplained muscle pain, tenderness or weakness occurs. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- Major warning · Obtain liver enzymes before starting and repeat as clinically indicated; interrupt treatment for serious liver injury with symptoms, hyperbilirubinemia or jaundice. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
Drug interactions
- ModerateStrong CYP3A4 inhibitors
Mechanism: They increase lovastatin exposure and the risk of myopathy or rhabdomyolysis.
Recommendation: Do not combine; suspend lovastatin during an unavoidable short course.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- HighGemfibrozil, other fibrates or niacin ≥1 g/day
Mechanism: They increase the risk of myopathy and rhabdomyolysis.
Recommendation: Avoid gemfibrozil and strictly assess other combinations.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- HighDiltiazem, dronedarone, verapamil or danazol
Mechanism: They increase muscle toxicity risk with lovastatin.
Recommendation: Start at 10 mg and do not exceed 20 mg/day.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- HighCyclosporine
Mechanism: It increases lovastatin exposure and the risk of myopathy or rhabdomyolysis.
Recommendation: Avoid the combination.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- HighAmiodaroneC01BD01
Mechanism: It increases the risk of lovastatin-associated myopathy and rhabdomyolysis.
Recommendation: Do not exceed lovastatin 40 mg/day.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- HighGrapefruit or grapefruit juice
Mechanism: It may increase lovastatin concentrations through CYP3A4 inhibition.
Recommendation: Avoid grapefruit during treatment.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- ModerateCoumarin anticoagulants
Mechanism: Lovastatin may increase prothrombin time and INR.
Recommendation: Check PT/INR before initiation and during dose changes until stable.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
- HighColchicine or ranolazine
Mechanism: Cases of myopathy and rhabdomyolysis have been reported with the combination.
Recommendation: With ranolazine, consider adjusting the lovastatin dose. With either combination, assess benefit, monitor for muscle symptoms and discontinue if myopathy is suspected.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9438d8a0-ca5b-4676-aab9-d0241ccff6c9
Adverse events
Common (≥1%)
Flatulence · Headache · Myalgia · Abdominal pain · Constipation · Diarrhea · Nausea
Rare but serious
Rhabdomyolysis or immune-mediated necrotizing myopathy · Severe hepatic failure · Anaphylaxis, angioedema or severe skin reaction
Pregnancy and lactation
FDA category: X
Contraindicated during pregnancy; discontinue immediately if pregnancy is recognized. Do not breastfeed during treatment because of the risk of serious reactions in the infant.
Recent literature (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.