Statins : Administration Time & Equivalence

• Statins lower cholesterol levels through inhibition of HMG-CoA reductase.
• 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.
• LDL-C and TC lowering was significantly greater in the evening dose than in the morning dose in case of short-acting statins. Besides slight but significant effect on LDL-C, the efficacy of long-acting statins was equivalent for both regimens. Therefore, long-acting statins should be given at a time that will best aid compliance. Short-acting statins should be given in the evening.
• The half-life of atorvastatin is about 14 hours, while its active metabolites have a half-life of about 20 to 30 hours. 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.
• Simvastatin is a prodrug activated by first-pass hepatic metabolism to a hydroxyacid metabolite, which has a half-life of 1–2 hours.

Statin	Half-Life	Suggested Time of Administration
Lovastatin (Mevacor)	1.1 – 1.7 hours	Night
Simvastatin (Zocor)	3 hours	Night
Fluvastatin (Lescol)	IR: <3 hours ER: 9 hours	Night
Pitavastatin (Livalo)	12 hours	Anytime
Atorvastatin (Lipitor)	Parent Drug: 14 hours Metabolites: 20 – 30 hours	Anytime
Rosuvastatin (Crestor)	19 hours	Anytime
Pravastatin (Pravachol)	77 hours	Anytime

Table: Half-life and suggested administration

Statin	Dosage
	Low-intensity (LDL-C reduction <30%)	Moderate-intensity (LDL-C reduction 30% to <50%)	High-intensity (LDL-C reduction >50%)
Atorvastatin	NA	10 to 20 mg	40 to 80 mg
Fluvastatin	20 to 40 mg	40 mg 2×/day; XL 80 mg	NA
Lovastatin	20 mg	40 mg	NA
Pitavastatin	1 mg	2 to 4 mg	NA
Pravastatin	10 to 20 mg	40 to 80 mg	NA
Rosuvastatin	NA	5 to 10 mg	20 to 40 mg
Simvastatin	10 mg	20 to 40 mg	NA

Table: Statin Dosing and ACC/AHA Classification of Intensity, 2013

References:

1.        Awad, K., Serban, M.-C., Penson, P., Mikhailidis, D. P., Toth, P. P., Jones, S. R., Rizzo, M., Howard, G., Lip, G. Y. H., &Banach, M. (2017). Effects of morning vs evening statin administration on lipid profile: A systematic review and meta-analysis. Journal of Clinical Lipidology, 11(4), 972–985.e9. https://doi.org/10.1016/j.jacl.2017.06.001

2.        Chou R, Dana T, Blazina I, et al. Statin Use for the Prevention of Cardiovascular Disease in Adults: A Systematic Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 Nov. (Evidence Syntheses, No. 139.) Table 1, Statin Dosing and ACC/AHA Classification of Intensity. Available from: https://www.ncbi.nlm.nih.gov/books/NBK396417/table/ch1.t1/

3.        Plakogiannis, R., & Cohen, H. (2007). Optimal low-density lipoprotein cholesterol lowering--morning versus evening statin administration. The Annals of pharmacotherapy, 41(1), 106–110. https://doi.org/10.1345/aph.1G659

4.        Which Statin Is the Best Choice for Which Patient? (2014). American Family Physician, 65(6), 1211. https://www.aafp.org/afp/2002/0315/p1211.html

5.        (n.d.). Statin Dose Intensity and Equivalency Chart [Review of Statin Dose Intensity and Equivalency Chart]. UMHS Lipid Therapy Guideline. http://www.mqic.org/pdf/UMHS_Statin_Dose_Intensity_and_Equivalency_Chart.pdf

All information accessed on 17 July 2020 [Prepared by Noratikah ; Edited by JCK Ho]