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simvastatin

MedGen UID:
22968
Concept ID:
C0074554
Organic Chemical; Pharmacologic Substance
Synonyms: zocor
Drug response:
Simvastatin response
MedGen UID:
472073
Concept ID:
CN128903
Sign or Symptom
Statins are among the most commonly prescribed drugs in the world to treat hypercholesterolemia and prevent cardiovascular diseases. They effectively lower cholesterol levels by inhibiting the HMG-CoA reductase to reduce cholesterol synthesis. Though well tolerated in general, the most common statin side effect is muscle pain. The symptoms range from mild muscle pain to fatal rhabdomyolysis, especially when statins are administered at higher doses and with certain other medications. A common coding SNP in the SLCO1B1 gene, rs4149056 or SLCO1B1*5, has been significantly associated with a marked increase in systemic exposure to simvastatin and risk of muscle toxicity. The overall effect size and significance of this association are striking for simvastatin compared to other statins. Patients with this specific variant in SLCO1B1 (a transporter of simvastatin) may require a lower simvastatin dose or consider an alternative statin as compared to patients who do not have this variant, and may consider routine creatine kinase (CK) surveillance. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published a clinical dosing guideline for SLCO1B1 genotype and simvastatin dosing in Clinical Pharmacology & Therapeutics. This guideline is available on the PharmGKB website.
Statin-induced myopathy
MedGen UID:
507347
Concept ID:
CN181199
Sign or Symptom
SNOMED CT: Simvastatin (387584000); Simvastatin (96304005)
 

Definition

A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL. [from MeSH]

Recent clinical studies

Etiology

Chan D, Binks S, Nicholas JM, Frost C, Cardoso MJ, Ourselin S, Wilkie D, Nicholas R, Chataway J
Lancet Neurol 2017 Aug;16(8):591-600. Epub 2017 Jun 7 doi: 10.1016/S1474-4422(17)30113-8. PMID: 28600189Free PMC Article
Chen W, Huang Z, Bi M, Xu X, Zhao N
Lipids Health Dis 2017 Mar 13;16(1):53. doi: 10.1186/s12944-017-0439-0. PMID: 28288631Free PMC Article
Florentin M, Elisaf MS, Rizos CV, Nikolaou V, Bilianou E, Pitsavos C, Liberopoulos EN
Lipids 2017 Jan;52(1):1-9. Epub 2016 Dec 2 doi: 10.1007/s11745-016-4216-z. PMID: 27914033
Li K, Liu Y, Venners SA, Hsu YH, Jiang S, Weinstock J, Sun Y, Wang B, Xu X
Clin Appl Thromb Hemost 2017 May;23(4):336-344. Epub 2016 Mar 16 doi: 10.1177/1076029616638504. PMID: 26984935
Alexander ZE, Su'a B, Hill CT, Lyndon MP, Singh PP, Hill AG
J Surg Res 2016 Sep;205(1):28-32. Epub 2016 May 26 doi: 10.1016/j.jss.2016.05.037. PMID: 27620995

Diagnosis

Hoppe C, Jacob E, Styles L, Kuypers F, Larkin S, Vichinsky E
Br J Haematol 2017 May;177(4):620-629. Epub 2017 Mar 28 doi: 10.1111/bjh.14580. PMID: 28369718Free PMC Article
Xian G, Zhao J, Qin C, Zhang Z, Lin Y, Su Z
Cancer Lett 2017 Jan 28;385:65-74. Epub 2016 Nov 11 doi: 10.1016/j.canlet.2016.11.006. PMID: 27840243
Yang X, Yin M, Yu L, Lu M, Wang H, Tang F, Zhang Y
Can J Physiol Pharmacol 2016 Dec;94(12):1336-1343. Epub 2016 Aug 16 doi: 10.1139/cjpp-2016-0295. PMID: 27733051
Hernandez-Mijares A, Bañuls C, Rovira-Llopis S, Diaz-Morales N, Escribano-Lopez I, de Pablo C, Alvarez A, Veses S, Rocha M, Victor VM
Atherosclerosis 2016 Apr;247:40-7. Epub 2016 Feb 4 doi: 10.1016/j.atherosclerosis.2016.01.044. PMID: 26868507
Yang ZX, Wang YZ, Jia BB, Mao GX, Lv YD, Wang GF, Yu H
Geriatr Gerontol Int 2016 Mar;16(3):322-8. Epub 2015 Feb 27 doi: 10.1111/ggi.12472. PMID: 25727911

Therapy

Hoppe C, Jacob E, Styles L, Kuypers F, Larkin S, Vichinsky E
Br J Haematol 2017 May;177(4):620-629. Epub 2017 Mar 28 doi: 10.1111/bjh.14580. PMID: 28369718Free PMC Article
Jiang F, Choi JY, Lee JH, Ryu S, Park ZW, Lee JG, Na HS, Lee SY, Oh WY, Chung MW, Choi SE
Pharmacogenomics 2017 Apr;18(5):459-469. Epub 2017 Mar 28 doi: 10.2217/pgs-2016-0199. PMID: 28350522
Chen W, Huang Z, Bi M, Xu X, Zhao N
Lipids Health Dis 2017 Mar 13;16(1):53. doi: 10.1186/s12944-017-0439-0. PMID: 28288631Free PMC Article
Morel J, Hargreaves I, Brealey D, Neergheen V, Backman JT, Lindig S, Bläss M, Bauer M, McAuley DF, Singer M
Clin Sci (Lond) 2017 Apr 25;131(8):747-758. Epub 2017 Feb 15 doi: 10.1042/CS20160802. PMID: 28202686
Li K, Liu Y, Venners SA, Hsu YH, Jiang S, Weinstock J, Sun Y, Wang B, Xu X
Clin Appl Thromb Hemost 2017 May;23(4):336-344. Epub 2016 Mar 16 doi: 10.1177/1076029616638504. PMID: 26984935

Prognosis

Miyazawa Y, Sekine Y, Kato H, Furuya Y, Koike H, Suzuki K
Prostate 2017 Mar;77(4):337-349. Epub 2016 Nov 8 doi: 10.1002/pros.23273. PMID: 27862098
Geboers S, Stappaerts J, Tack J, Annaert P, Augustijns P
Int J Pharm 2016 Aug 20;510(1):296-303. Epub 2016 Jun 20 doi: 10.1016/j.ijpharm.2016.06.048. PMID: 27340029
Murphy SA, Cannon CP, Blazing MA, Giugliano RP, White JA, Lokhnygina Y, Reist C, Im K, Bohula EA, Isaza D, Lopez-Sendon J, Dellborg M, Kher U, Tershakovec AM, Braunwald E
J Am Coll Cardiol 2016 Feb 2;67(4):353-61. doi: 10.1016/j.jacc.2015.10.077. PMID: 26821621
Wang T, Seah S, Loh X, Chan CW, Hartman M, Goh BC, Lee SC
Oncotarget 2016 Jan 19;7(3):2532-44. doi: 10.18632/oncotarget.6304. PMID: 26565813Free PMC Article
Pek SL, Tavintharan S, Woon K, Lin L, Ong CN, Lim SC, Sum CF
Exp Biol Med (Maywood) 2016 Feb;241(3):317-30. Epub 2015 Sep 30 doi: 10.1177/1535370215605588. PMID: 26429200Free PMC Article

Clinical prediction guides

Chan D, Binks S, Nicholas JM, Frost C, Cardoso MJ, Ourselin S, Wilkie D, Nicholas R, Chataway J
Lancet Neurol 2017 Aug;16(8):591-600. Epub 2017 Jun 7 doi: 10.1016/S1474-4422(17)30113-8. PMID: 28600189Free PMC Article
Hoppe C, Jacob E, Styles L, Kuypers F, Larkin S, Vichinsky E
Br J Haematol 2017 May;177(4):620-629. Epub 2017 Mar 28 doi: 10.1111/bjh.14580. PMID: 28369718Free PMC Article
Florentin M, Elisaf MS, Rizos CV, Nikolaou V, Bilianou E, Pitsavos C, Liberopoulos EN
Lipids 2017 Jan;52(1):1-9. Epub 2016 Dec 2 doi: 10.1007/s11745-016-4216-z. PMID: 27914033
Xian G, Zhao J, Qin C, Zhang Z, Lin Y, Su Z
Cancer Lett 2017 Jan 28;385:65-74. Epub 2016 Nov 11 doi: 10.1016/j.canlet.2016.11.006. PMID: 27840243
Montaner J, Bustamante A, García-Matas S, Martínez-Zabaleta M, Jiménez C, de la Torre J, Rubio FR, Segura T, Masjuán J, Cánovas D, Freijo M, Delgado-Mederos R, Tejada J, Lago A, Bravo Y, Corbeto N, Giralt D, Vives-Pastor B, de Arce A, Moniche F, Delgado P, Ribó M; STARS Investigators.
Stroke 2016 Nov;47(11):2870-2873. Epub 2016 Oct 6 doi: 10.1161/STROKEAHA.116.014600. PMID: 27758944

Recent systematic reviews

Chen W, Huang Z, Bi M, Xu X, Zhao N
Lipids Health Dis 2017 Mar 13;16(1):53. doi: 10.1186/s12944-017-0439-0. PMID: 28288631Free PMC Article
Ong YC, Aziz Z
J Clin Pharm Ther 2016 Apr;41(2):170-9. Epub 2016 Mar 9 doi: 10.1111/jcpt.12374. PMID: 26956355
Karlson BW, Palmer MK, Nicholls SJ, Lundman P, Barter PJ
Eur J Prev Cardiol 2016 May;23(7):744-7. Epub 2015 Aug 5 doi: 10.1177/2047487315598710. PMID: 26246463
Thomopoulos C, Skalis G, Michalopoulou H, Tsioufis C, Makris T
Clin Cardiol 2015 Dec;38(12):763-9. Epub 2015 Aug 18 doi: 10.1002/clc.22441. PMID: 26282344
Ma N, Cui L
Drug Des Devel Ther 2015;9:1859-64. Epub 2015 Mar 31 doi: 10.2147/DDDT.S67448. PMID: 25848221Free PMC Article

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