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Why are Some Statins Recommended to be Taken at Nighttime?


  • Endogenous cholesterol synthesis is cyclical in nature with the greatest production during fasting states.  

  • The elimination half-lives of statins determine if an agent should be dosed at bedtime. 

  • To maximize the effects of statins with a short half-life, fluvastatin, lovastatin, and simvastatin should be dosed at bedtime allowing the greatest drug concentration to be present during peak endogenous cholesterol synthesis.

  • The long half-life of atorvastatin, pitavastatin, pravastatin, and rosuvastatin allows for flexibility in administration time.

  Carolyn J. Steber, PharmD
Editor-in-Chief:  Anthony J. Busti, MD, PharmD, FNLA, FAHA
Content Editors: Donald S. Nuzum, PharmD, BCACP, BC-ADM, CDE, CPP and Sabrina W. Cole, PharmD, BCPS
Last Reviewed:  August 2015


  • Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, more commonly known as statins, are recommended as first-line agents in the reduction of low-density lipoprotein cholesterol (LDL-C).(1)  Although cholesterol is imperative for normal cellular function, excess LCL-C leads to atherogenesis.  Plaque formation in the arteries results in coronary artery disease (CAD), heart attack, and/or stroke.  There is known morbidity and mortality benefit associated with LDL-C reduction from statin therapy; therefore, it is vital that patients take the medication in a way that provides the greatest effect.(2)

    Although some cholesterol comes from dietary intake, a significant amount is produced endogenously.  It was previously hypothesized that human cholesterol production may be cyclical in nature mimicking the confirmed pattern of cholesterol synthesis in animals.  Human trials then confirmed the fluctuation in cholesterol synthesis, noting the greatest cholesterol production from the liver during fasting states.

    The apparent circadian rhythm of cholesterol production sparked the recommendation that statins be dosed at bedtime to provide the greatest medication concentration when endogenous cholesterol production is the highest.(3)

    Investigation of pharmacokinetic properties of individual statins disproved the need for all agents to be dosed at bedtime.(1)  Although all statins go through hepatic metabolism, the elimination half-lives vary in length.  Simvastatin, fluvastatin, and lovastatin have a short elimination half-life compared to other drugs within the class.  Agents with significantly shorter elimination half-lives require bedtime dosing to maximize efficacy - allowing the greatest statin concentration to be present while endogenous cholesterol synthesis is the highest.  Alternatively, the longer half-lives of rosuvastatin, atorvastatin, pitavastatin, and pravastatin allow these agents to maintain a therapeutic drug concentration over a 24-hour period and allow alternate administration times.(2)

    Even if properly counseled to take statins with a shorter half-life at bedtime, some patients do not comply which may result in decreased efficacy.  Agents with longer half-lives allow for greater flexibility in administration time, which may improve compliance and ultimately result in greater LDL-C reduction and ability to achieve cholesterol goals.



    1. Expert panel on the detection, evaluation, and treatment of high blood cholesterol in adults: executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high cholesterol in adults (adult treatment panel III).  JAMA.  2001:285:2486-2497.
    2. Plakogiannis R, Cohen H.  Optimal low-density lipoprotein cholesterol lowering - morning versus  evening statin administration.  Ann Pharmacother.  2007;41:106-110. 
    3. Jones PJ, Schoeller DA.  Evidence for diurnal periodicity in human cholesterol synthesis.  J Lipid Res. 1990;31:667-673.
    4. Brunton LL, Chabner BA, Knollmann BC, eds.  Goodman & Gilman's The Pharmacological Basis of Therapeutics.  12th ed.  New York: McGraw-Hill;2011.
    5. Kalant H, Grant DM, Mitchell J.  Principles of Medical Pharmacology.  7th ed.  Toronto: Saunders Elsevier;2007

MESH Terms & Keywords

  • Statin, HMG-CoA Reductase Inhibitors, Nighttime Drug Administration, Lovastatin, Simvastatin, Fluvastatin, Pitavastatin, Atorvastatin, Rosuvastatin, Pravastatin, Crestor, Lipitor, Zocor, Livalo