Chemical: Drug
simvastatin

last updated 06/30/2014

1. CPIC Guideline for simvastatin and SLCO1B1

Summary

The FDA recommends against 80mg daily simvastatin dosage. In patients with the C allele at SLCO1B1 rs4149056, there are modest increases in myopathy risk even at lower simvastatin doses (40mg daily); if optimal efficacy is not achieved with a lower dose, alternate agents should be considered.

Annotation

October 2014 Update

Advance online publication 9 July 2014.

  • The 2014 update of CPIC guideline regarding SLCO1B1 and simvastatin-induced myopathy, has been published in Clinical Pharmacology and Therapeutics. CPIC extensively reviewed the literature from February 2011 to December 2013 and concluded the dosing recommendations provided in the 2012 CPIC guideline for SLCO1B1 and simvastatin-induced myopathy have not changed. However, this updated guideline also provides a brief review regarding SLCO1B1 genotype and risk of myopathy for other statins. Furthermore, comprehensive translation tables mapping SLCO1B1 genotypes to coded genotype/phenotype summaries, EHR priority result notation and interpretation (consultation) text were created to facilitate incorporation of SLCO1B1 pharmacogenetics into an electronic health record with clinical decision support.

  • This guideline is applicable to:

    • adult patients
    • pediatric patients
  • Excerpt from the 2014 simvastatin dosing guideline:

    • "For simvastatin, the evidence linking myopathy to rs4149056 in SLCO1B1 is of high quality, and this association has been reproduced in randomized trials and clinical practice-based cohorts. Conversely, the association of rs4149056 with myopathy has been less compelling for other statins. We therefore focus this guideline on simvastatin."

"In 2011 and updated in 2013, the FDA added warnings to the simvastatin product label to direct providers away from initiating at the 80 mg simvastatin dose. "

"At lower simvastatin doses (e.g., 40 mg daily), it is our position that SLCO1B1 genotype (if available) could be used to warn providers about modest increases in myopathy risk for patients with a C allele at rs4149056. In these circumstances, we recommend a lower dose of simvastatin or use an alternative statin (e.g. pravastatin or rosuvastatin) and we also highlight the potential utility of routine CK surveillance (Table 2). If patients with a C allele at rs4149056 do not achieve optimal LDL cholesterol-lowering efficacy with a lower dose (e.g. 20 mg) of simvastatin, we recommend the prescribing physician consider an alternate statin based on (i) potency differences (i.e., use a lower dose of a higher potency statin such as atorvastatin, rosuvastatin, or pitavastatin), (ii) drug-drug interactions (e.g., boceprevir, clarithromycin, cyclosporine, strong CYP3A4 inhibitors, etc.), and (iii) relevant co-morbidities (e.g., trauma, significant renal impairment, post-solid organ transplant, thyroid disease etc.)."

"At the time of this writing, there are no data available regarding SLCO1B1 genotype effects on simvastatin response or myopathy in pediatric patient populations, although there is no reason to suspect that the polymorphisms in SLCO1B1 will affect simvastatin's metabolism differently in children compared to adults."

Table 1: Recommended dosing of simvastatin based on SLCO1B1 phenotype

Adapted from Table 1 and 2 of the 2014 guideline update manuscript.

PhenotypeExamples of diplotypes aGenotype at rs4149056Implications for simvastatinDosing recommendations for simvastatin b,cClassification of recommendations d
Normal function, Homozygous wild-type (two normal function alleles)*1a/*1a, *1a/*1b, *1b/*1bTTNormal myopathy riskPrescribe desired starting dose and adjust doses of simvastatin based on disease-specific guidelines.Strong
Intermediate function, Heterozygous (one normal function allele plus one decreased function allele)*1a/*5, *1a/*15, *1a/*17, *1b/*5, *1b/*15, *1b/*17TCIntermediate myopathy riskPrescribe a lower dose or consider an alternative statin (e.g. pravastatin or rosuvastatin); consider routine CK surveillance.Strong
Low function, Homozygous variant or mutant (two decreased function alleles)*5/*5, *5/*15, *5/*17, *15/*15, *15/*17, *17/*17CCHigh myopathy riskPrescribe a lower dose or consider an alternative statin (e.g. pravastatin or rosuvastatin); consider routine CK surveillance.Strong

CK, creatine kinase.

a SLCO1B1 alleles are often named using __ allele nomenclature, representing various SNPs alone or in combination (http://www.pharmgkb.org/gene/PA134865839#tabview=tab4&subtab=33) (2014 Update Supplemental Table S1) that are associated with low SLCO1B1 protein expression or function (2014 Update Supplemental Table S2). The minor C allele at rs4149056 is contained within SLCO1B1*5 (rs4149056 alone) as well as the *15 and *17 haplotypes and is associated with lower plasma clearance of simvastatin. The magnitude of this effect is similar for *5, *15, and *17 haplotypes.

b In all cases, the potential for drug-drug interaction should be evaluated prior to initiating a prescription.

c FDA recommends against 80mg (unless already tolerated 12 months).

d See Supplementary Materials (text section entitled "Levels of Evidence") online for additional details regarding the three-tiered system used to grade the quality of evidence.

July 2012

Advance online publication May 2012.



1. FDA Label for simvastatin

Full label available at DailyMed

Genes and/or phenotypes found in this label


Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for simvastatin

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA ABCB1 *1 N/A N/A N/A
No VIP available No VIP available VA ABCB1 *2 (PMID: 11503014) N/A N/A N/A
No VIP available No VIP available VA ABCB1 *2 (PMID: 12893986) N/A N/A N/A
No VIP available CA VA ABCC2 H2 N/A N/A N/A
No VIP available CA VA ABCC2 H12 N/A N/A N/A
No VIP available CA VA APOE E2 N/A N/A N/A
No VIP available CA No VIP available APOE E3 N/A N/A N/A
No VIP available CA VA APOE E4 N/A N/A N/A
No VIP available No VIP available VA CYP2C8 *3 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *2 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *3 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *4 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *14 N/A N/A N/A
No VIP available CA VA CYP3A4 *1 N/A N/A N/A
No VIP available No VIP available VA CYP3A4 *1G N/A N/A N/A
No VIP available CA VA CYP3A4 *4 N/A N/A N/A
No VIP available CA VA CYP3A4 *22 N/A N/A N/A
No VIP available No VIP available VA CYP3A5 *1A N/A N/A N/A
No VIP available No VIP available VA CYP3A5 *3A N/A N/A N/A
No VIP available CA VA HMGCR H2 N/A N/A N/A
No VIP available CA VA HMGCR H7 N/A N/A N/A
No VIP available CA VA LDLR L5 N/A N/A N/A
No VIP available CA VA SLCO1B1 *1 N/A N/A N/A
No VIP available CA No VIP available SLCO1B1 *2 N/A N/A N/A
No VIP available No VIP available VA SLCO1B1 *5 N/A N/A N/A
No VIP available CA VA
rs1045642 NC_000007.13:g.87138645A>G, NC_000007.14:g.87509329A>G, NG_011513.1:g.208920T>C, NM_000927.4:c.3435T>C, NP_000918.2:p.Ile1145=, rs10239679, rs11568726, rs117328163, rs17210003, rs2229108, rs386513066, rs60023214, rs9690664
A > G
SNP
I1145I
No VIP available CA No Variant Annotations available
rs1057910 NC_000010.10:g.96741053A=, NC_000010.10:g.96741053A>C, NC_000010.11:g.94981296A=, NC_000010.11:g.94981296A>C, NG_008385.1:g.47639A=, NG_008385.1:g.47639A>C, NM_000771.3:c.1075A=, NM_000771.3:c.1075A>C, NP_000762.2:p.Ile359=, NP_000762.2:p.Ile359Leu, XM_005269575.1:c.1075A=, XM_005269575.1:c.1075A>C, XP_005269632.1:p.Ile359=, XP_005269632.1:p.Ile359Leu, rs17847042, rs3198471, rs61212474
A > C
SNP
I359L
No VIP available No Clinical Annotations available VA
rs1063320 NC_000006.11:g.29798749C=, NC_000006.11:g.29798749C>G, NC_000006.12:g.29830972C=, NC_000006.12:g.29830972C>G, NG_029039.1:g.8994C=, NG_029039.1:g.8994C>G, NM_002127.5:c.*233C=, NM_002127.5:c.*233C>G, NT_113891.3:g.1314548G=, NT_113891.3:g.1314548G>C, NT_167244.2:g.1096598G=, NT_167244.2:g.1096598G>C, NT_167245.1:g.1099370C=, NT_167245.1:g.1099370C>G, NT_167245.2:g.1093785C=, NT_167245.2:g.1093785C>G, NT_167246.1:g.1099078C=, NT_167246.1:g.1099078C>G, NT_167246.2:g.1093458C=, NT_167246.2:g.1093458C>G, NT_167247.1:g.1099028C=, NT_167247.1:g.1099028C>G, NT_167247.2:g.1093443C=, NT_167247.2:g.1093443C>G, NT_167248.2:g.1093752G=, NT_167248.2:g.1093752G>C, NT_167249.2:g.1137017G=, NT_167249.2:g.1137017G>C, XM_005249055.1:c.*233C=, XM_005249055.1:c.*233C>G, XM_005249056.1:c.*233C>G, XM_005249056.1:c.*233G>C, XM_005249057.1:c.*448C>G, XM_005249057.1:c.*448G>C, XM_005249058.1:c.*233C=, XM_005249058.1:c.*233C>G, XM_005272810.1:c.*247G=, XM_005272810.1:c.*247G>C, XM_005274964.1:c.*233C=, XM_005274964.1:c.*233C>G, XM_005274965.1:c.*233C=, XM_005274965.1:c.*233C>G, XM_005274966.1:c.*448C>G, XM_005274966.1:c.*448G>C, XM_005274967.1:c.*233C=, XM_005274967.1:c.*233C>G, XM_005275119.1:c.*233C=, XM_005275119.1:c.*233C>G, XM_005275120.1:c.*233C>G, XM_005275120.1:c.*233G>C, XM_005275121.1:c.*448C>G, XM_005275121.1:c.*448G>C, XM_005275122.1:c.*233C>G, XM_005275122.1:c.*233G>C, XM_005275246.1:c.*233C=, XM_005275246.1:c.*233C>G, XM_005275247.1:c.*233C=, XM_005275247.1:c.*233C>G, XM_005275248.1:c.*448C>G, XM_005275248.1:c.*448G>C, XM_005275249.1:c.*233C=, XM_005275249.1:c.*233C>G, XM_005275394.1:c.*247G=, XM_005275394.1:c.*247G>C, XM_005275549.1:c.*247G=, XM_005275549.1:c.*247G>C, XM_005275550.1:c.*247C>G, XM_005275550.1:c.*247G>C, XM_005275551.1:c.*462C>G, XM_005275551.1:c.*462G>C, XM_005275552.1:c.*247G=, XM_005275552.1:c.*247G>C, XM_011547651.1:c.*233C=, XM_011547651.1:c.*233C>G, XM_011547882.1:c.*233C=, XM_011547882.1:c.*233C>G, XM_011548048.1:c.*233C=, XM_011548048.1:c.*233C>G, XM_011548236.1:c.*247G=, XM_011548236.1:c.*247G>C, XM_011548237.1:c.*247G=, XM_011548237.1:c.*247G>C, XM_011548430.1:c.*247G=, XM_011548430.1:c.*247G>C, XM_011548431.1:c.*247G=, XM_011548431.1:c.*247G>C, XR_241896.1:n.1859C=, XR_241896.1:n.1859C>G, XR_246963.1:n.1793G=, XR_246963.1:n.1793G>C, XR_247353.1:n.1859C=, XR_247353.1:n.1859C>G, XR_247370.1:n.1859C=, XR_247370.1:n.1859C>G, XR_247389.1:n.1859C=, XR_247389.1:n.1859C>G, XR_247402.1:n.1793G=, XR_247402.1:n.1793G>C, XR_247423.1:n.1851G=, XR_247423.1:n.1851G>C, rs115928989, rs117512550, rs1632929, rs16867727, rs17185496, rs3204385, rs386485817, rs58677621, rs9258500
C > C
C > G
SNP
No VIP available CA VA
rs1128503 NC_000007.13:g.87179601A>G, NC_000007.14:g.87550285A>G, NG_011513.1:g.167964T>C, NM_000927.4:c.1236T>C, NP_000918.2:p.Gly412=, rs116989428, rs17276907, rs2032587, rs2229105, rs28365046, rs386518005, rs58257317
A > G
SNP
G412G
No VIP available CA VA
rs1137101 NC_000001.10:g.66058513A>G, NC_000001.11:g.65592830A>G, NG_015831.2:g.177266A>G, NM_001003679.3:c.668A>G, NM_001003680.3:c.668A>G, NM_001198687.1:c.668A>G, NM_001198688.1:c.668A>G, NM_001198689.1:c.668A>G, NM_002303.5:c.668A>G, NP_001003679.1:p.Gln223Arg, NP_001003680.1:p.Gln223Arg, NP_001185616.1:p.Gln223Arg, NP_001185617.1:p.Gln223Arg, NP_001185618.1:p.Gln223Arg, NP_002294.2:p.Gln223Arg, XM_005270950.1:c.668A>G, XM_005270951.1:c.668A>G, XM_005270952.1:c.668A>G, XP_005271007.1:p.Gln223Arg, XP_005271008.1:p.Gln223Arg, XP_005271009.1:p.Gln223Arg, rs12131454, rs17356624, rs1805093, rs2229418, rs3200842, rs52820808, rs59347832, rs9282885
A > G
SNP
Q223R
No VIP available No Clinical Annotations available VA
rs1150226 NC_000011.10:g.113974819A>G, NC_000011.9:g.113845541A>G, NG_013058.1:g.4745A>G, NM_000869.5:c.-489A>G, NM_213621.3:c.-489A>G, NR_046363.1:n.-256A>G, rs1456890, rs1672729, rs386518532, rs56774067
A > G
SNP
No VIP available CA VA
rs11716445 NC_000003.11:g.49406095G>A, NC_000003.12:g.49368662G>A, NM_001313941.1:c.157-114C>T, NM_001313943.1:c.157-114C>T, NM_001313944.1:c.130-147C>T, NM_001313945.1:c.-87-114C>T, NM_001313946.1:c.156+6772C>T, NM_001313947.1:c.157-6036C>T, NM_001664.3:c.157-114C>T, XM_005265116.1:c.130-147C>T, XM_011533695.1:c.157-114C>T, rs56548113, rs58714945
G > A
SNP
No VIP available No Clinical Annotations available VA
rs11807862 NC_000001.10:g.3279268T>A, NC_000001.11:g.3362704T>A, NG_029576.1:g.298527T>A, NM_022114.3:c.439-22448T>A, NM_199454.2:c.439-22448T>A, XM_005244772.1:c.439-22445T>A, XM_005244772.3:c.439-22445T>A, XM_005244773.1:c.439-22445T>A, XM_005244773.3:c.439-22445T>A, XM_005244774.1:c.439-22445T>A, XM_005244774.3:c.439-22445T>A, XM_006710814.2:c.439-22445T>A, XM_011541944.1:c.439-22445T>A, XM_011541945.1:c.-114-22448T>A, rs57382713
T > A
SNP
No VIP available CA VA
rs12003906 NC_000009.11:g.107645477G>T, NC_000009.12:g.104883196G>T, NG_007981.1:g.49960C>A, NM_005502.3:c.303-39C>A, XM_005251773.1:c.303-39C>A, XM_005251774.1:c.303-39C>A, XM_005251775.1:c.240-39C>A, XM_005251776.1:c.123-39C>A, XM_005251777.1:c.303-39C>A, XM_005251778.1:c.303-39C>A, XM_005251780.1:c.303-39C>A, XM_011518339.1:c.378-39C>A, XM_011518340.1:c.378-39C>A, XM_011518341.1:c.378-39C>A, XM_011518342.1:c.-61-39C>A, XM_011518343.1:c.378-39C>A, XM_011518344.1:c.378-39C>A, rs58402594
G > C
G > T
SNP
No VIP available No Clinical Annotations available VA
rs12052787 NC_000002.11:g.234666581C>T, NC_000002.12:g.233757935C>T, NG_002601.2:g.173192C>T, NG_033238.1:g.2663C>T, NM_001072.3:c.862-9099C>T, NM_007120.2:c.868-9099C>T, NM_019075.2:c.856-9099C>T, NM_019076.4:c.856-9099C>T, NM_019077.2:c.856-9099C>T, NM_019078.1:c.868-9099C>T, NM_019093.2:c.868-9099C>T, NM_021027.2:c.856-9099C>T, NM_205862.1:c.61-9099C>T, XR_241238.1:n.924-9099C>T, XR_241240.1:n.1023-9099C>T, XR_241241.1:n.942-9099C>T, rs386522690
C > T
SNP
No VIP available No Clinical Annotations available VA
rs12422149 NC_000011.10:g.75172532G>A, NC_000011.9:g.74883577G>A, NG_027921.1:g.26546G>A, NM_001145211.2:c.869G>A, NM_001145212.2:c.503G>A, NM_007256.4:c.935G>A, NP_001138683.1:p.Arg290Gln, NP_001138684.1:p.Arg168Gln, NP_009187.1:p.Arg312Gln, XM_005273732.1:c.587G>A, XP_005273789.1:p.Arg196Gln, rs56415681, rs59614522
G > A
SNP
R290Q
No VIP available CA VA
rs12487736 NC_000003.11:g.47459679C>T, NC_000003.12:g.47418189C>T, NM_001320044.1:c.1627G>A, NM_012235.3:c.2392G>A, NP_001306973.1:p.Val543Ile, NP_036367.2:p.Val798Ile, XM_005264966.1:c.2392G>A, XM_005264967.1:c.2392G>A, XM_005264968.1:c.1627G>A, XM_005264969.1:c.1627G>A, XM_005264970.1:c.1216G>A, XM_005264970.3:c.1216G>A, XM_005264971.1:c.1216G>A, XM_005264972.1:c.1216G>A, XM_005264972.3:c.1216G>A, XM_011533501.1:c.2392G>A, XM_011533502.1:c.1249G>A, XP_005265023.1:p.Val798Ile, XP_005265024.1:p.Val798Ile, XP_005265025.1:p.Val543Ile, XP_005265026.1:p.Val543Ile, XP_005265027.1:p.Val406Ile, XP_005265028.1:p.Val406Ile, XP_005265029.1:p.Val406Ile, XP_011531803.1:p.Val798Ile, XP_011531804.1:p.Val417Ile, XR_940393.1:n.2578G>A, rs17845631, rs17849135, rs17858562
C > T
SNP
V543I
No VIP available CA VA
rs1346268 NC_000015.10:g.45380831T>C, NC_000015.9:g.45673029T>C, NG_011674.1:g.2952A>G, XM_011521450.1:c.32-262A>G, XM_011521451.1:c.36-272A>G, rs60883720
T > C
SNP
No VIP available No Clinical Annotations available VA
rs140700 NC_000017.10:g.28543389C>T, NC_000017.11:g.30216371C>T, NG_011747.2:g.24566G>A, NM_001045.5:c.838-155G>A, XM_005258025.1:c.964-155G>A, rs386530829, rs59205571
C > T
SNP
No VIP available No Clinical Annotations available VA
rs1440451 NC_000007.13:g.154868879G>C, NC_000007.14:g.155077169G>C, NG_044997.1:g.11846G>C, NM_024012.3:c.741+5529G>C, rs10321327, rs17837394, rs56554708, rs59321107, rs59745825
G > C
SNP
No VIP available CA VA
rs1719247 NC_000015.10:g.45328787C>T, NC_000015.9:g.45620985C>T, rs59060754
C > T
SNP
rs17238540 NC_000005.10:g.75359673T>G, NC_000005.9:g.74655498T>G, NG_011449.1:g.27506T>G, NM_000859.2:c.2457+117T>G, NM_001130996.1:c.2298+117T>G, XM_005248492.1:c.2517+117T>G, XM_011543357.1:c.2517+117T>G, XM_011543358.1:c.2457+117T>G, XM_011543359.1:c.2358+117T>G, rs59500163
T > G
SNP
No VIP available CA VA
rs17244841 NC_000005.10:g.75347030A>T, NC_000005.9:g.74642855A>T, NG_011449.1:g.14863A>T, NM_000859.2:c.451-174A>T, NM_001130996.1:c.451-174A>T, XM_005248492.1:c.511-174A>T, XM_011543357.1:c.511-174A>T, XM_011543358.1:c.451-174A>T, XM_011543359.1:c.511-174A>T, rs60168925
A > T
SNP
No VIP available CA VA
rs1800588 NC_000015.10:g.58431476C>T, NC_000015.9:g.58723675C>T, NG_011465.1:g.4501C>T, NM_000236.2:c.-557C>T, XM_005254372.1:c.-40-517C>T, XM_005254373.1:c.-40-517C>T, XM_011521551.1:c.-40-517C>T, XR_429537.2:n.-124G>A, XR_932289.1:n.-124G>A, rs52833592
C > T
SNP
No VIP available No Clinical Annotations available VA
rs1805054 NC_000001.10:g.19992513C>T, NC_000001.11:g.19666020C>T, NM_000871.2:c.267C>T, NP_000862.1:p.Tyr89=, rs58500287
C > T
SNP
Y89Y
No VIP available No Clinical Annotations available VA
rs1891311 NC_000010.10:g.92618616A>G, NC_000010.11:g.90858859A>G, NG_029218.1:g.4056T>C, NM_000872.4:c.-1188T>C, NM_019859.3:c.-1188T>C, NM_019860.3:c.-1188T>C, rs3824740, rs60062136
A > G
SNP
No VIP available CA VA
rs1935349 NC_000010.10:g.92594343C>T, NC_000010.11:g.90834586C>T, NG_029218.1:g.28329G>A, NM_000872.4:c.539+22547G>A, NM_019859.3:c.539+22547G>A, NM_019860.3:c.539+22547G>A, rs60894291
C > T
SNP
No VIP available CA VA
rs2003569 NC_000002.11:g.234667937G>A, NC_000002.12:g.233759291G>A, NG_002601.2:g.174548G>A, NG_033238.1:g.4019G>A, NM_000463.2:c.-997G>A, NM_001072.3:c.862-7743G>A, NM_007120.2:c.868-7743G>A, NM_019075.2:c.856-7743G>A, NM_019076.4:c.856-7743G>A, NM_019077.2:c.856-7743G>A, NM_019078.1:c.868-7743G>A, NM_019093.2:c.868-7743G>A, NM_021027.2:c.856-7743G>A, NM_205862.1:c.61-7743G>A, XR_241238.1:n.924-7743G>A, XR_241239.1:n.-975G>A, XR_241240.1:n.1023-7743G>A, XR_241241.1:n.942-7743G>A, rs17286591
G > A
SNP
No VIP available No Clinical Annotations available VA
rs2020933 NC_000017.10:g.28561755A>T, NC_000017.11:g.30234737A>T, NG_011747.2:g.6200T>A, NM_001045.5:c.-221+876T>A, XM_005258025.1:c.-95+876T>A, rs58019660
A > T
SNP
No VIP available CA VA
rs2032582 NC_000007.13:g.87160618A>C, NC_000007.13:g.87160618A>T, NC_000007.14:g.87531302A>C, NC_000007.14:g.87531302A>T, NG_011513.1:g.186947T>A, NG_011513.1:g.186947T>G, NM_000927.4:c.2677T>A, NM_000927.4:c.2677T>G, NP_000918.2:p.Ser893Ala, NP_000918.2:p.Ser893Thr, rs10228331, rs2229106, rs386553610, rs57135550, rs9641018
A > C
SNP
S893A
No VIP available No Clinical Annotations available VA
rs20455 NC_000006.11:g.39325078A>G, NC_000006.12:g.39357302A>G, NM_001289020.1:c.2104T>C, NM_001289021.1:c.1987T>C, NM_001289024.1:c.508T>C, NM_145027.4:c.2155T>C, NP_001275949.1:p.Trp702Arg, NP_001275950.1:p.Trp663Arg, NP_001275953.1:p.Trp170Arg, NP_659464.3:p.Trp719Arg, XM_005248904.1:c.2155T>C, XM_005248904.3:c.2155T>C, XM_005248905.1:c.2104T>C, XM_005248906.1:c.1987T>C, XM_011514357.1:c.2155T>C, XM_011514358.1:c.2155T>C, XM_011514359.1:c.2155T>C, XM_011514360.1:c.1528T>C, XP_005248961.1:p.Trp719Arg, XP_005248962.1:p.Trp702Arg, XP_005248963.1:p.Trp663Arg, XP_011512659.1:p.Trp719Arg, XP_011512660.1:p.Trp719Arg, XP_011512661.1:p.Trp719Arg, XP_011512662.1:p.Trp510Arg, rs16891985, rs56572561, rs58306844
A > G
SNP
W702R
No VIP available No Clinical Annotations available VA
rs2228314 NC_000022.10:g.42276742G>C, NC_000022.11:g.41880738G>C, NM_004599.3:c.1784G>C, NP_004590.2:p.Gly595Ala, NR_103834.1:n.2076G>C, XM_006724310.1:c.1694G>C, XM_011530347.1:c.1409G>C, XP_006724373.1:p.Gly565Ala, XP_011528649.1:p.Gly470Ala, rs11547819, rs4822063
G > -
G > C
SNP
G595A
No VIP available CA VA
rs2231142 NC_000004.11:g.89052323G>T, NC_000004.12:g.88131171G>T, NG_032067.2:g.105152C>A, NM_001257386.1:c.421C>A, NM_004827.2:c.421C>A, NP_001244315.1:p.Gln141Lys, NP_004818.2:p.Gln141Lys, XM_005263354.1:c.421C>A, XM_005263354.2:c.421C>A, XM_005263355.1:c.421C>A, XM_005263355.2:c.421C>A, XM_005263356.1:c.421C>A, XM_005263356.2:c.421C>A, XM_011532420.1:c.421C>A, XP_005263411.1:p.Gln141Lys, XP_005263412.1:p.Gln141Lys, XP_005263413.1:p.Gln141Lys, XP_011530722.1:p.Gln141Lys, rs12721641, rs28365035, rs3736117, rs52809243, rs58973676
G > T
SNP
Q141K
No VIP available CA VA
rs2276307 NC_000011.10:g.113933165A>G, NC_000011.9:g.113803887A>G, NG_011483.1:g.33299A>G, NM_006028.4:c.696+72A>G, XM_011543063.1:c.663+72A>G, XM_011543064.1:c.495+72A>G, XM_011543065.1:c.489+72A>G, XM_011543066.1:c.663+72A>G, rs60179104
A > G
SNP
rs2306283 NC_000012.11:g.21329738A>G, NC_000012.12:g.21176804A>G, NG_011745.1:g.50611A>G, NM_006446.4:c.388A>G, NP_006437.3:p.Asn130Asp, rs17389242, rs52832430, rs60767041
A > G
SNP
N130D
No VIP available CA VA
rs2740574 NC_000007.13:g.99382096C>T, NC_000007.14:g.99784473C>T, NG_008421.1:g.4713G>A, NM_001202855.2:c.-392G>A, NM_017460.5:c.-392G>A, XM_011515841.1:c.-392G>A, XM_011515842.1:c.-392G>A, rs3176920, rs36231114, rs59393892
C > T
SNP
No VIP available CA VA
rs2819742 NC_000001.10:g.237990122A>G, NC_000001.11:g.237826822A>G, NG_008799.2:g.789421A>G, NM_001035.2:c.14591-1559A>G, XM_005273224.1:c.14648-1559A>G, XM_006711802.2:c.14645-1559A>G, XM_006711803.2:c.14642-1559A>G, XM_006711804.2:c.14621-1559A>G, XM_006711805.2:c.14615-1559A>G, XM_006711806.2:c.14609-1559A>G, XM_006711807.2:c.14585-1559A>G, XM_006711808.2:c.14408-1559A>G, XM_006711810.2:c.14552-1559A>G, rs60098173, rs9428700
A > G
SNP
No VIP available CA VA
rs35599367 NC_000007.13:g.99366316G>A, NC_000007.14:g.99768693G>A, NG_008421.1:g.20493C>T, NM_001202855.2:c.522-191C>T, NM_017460.5:c.522-191C>T, XM_011515841.1:c.522-191C>T, XM_011515842.1:c.522-191C>T, rs45581939, rs62471940
G > A
SNP
No VIP available No Clinical Annotations available VA
rs3758987 NC_000011.10:g.113904553T>C, NC_000011.9:g.113775275T>C, NG_011483.1:g.4687T>C, NM_006028.4:c.-381T>C, XM_011543064.1:c.12+5470T>C, rs17542553, rs386585621, rs60662070
T > C
SNP
rs3846662 NC_000005.10:g.75355259A>G, NC_000005.9:g.74651084A>G, NG_011449.1:g.23092A>G, NM_000859.2:c.1722+45A>G, NM_001130996.1:c.1564-106A>G, XM_005248492.1:c.1782+45A>G, XM_011543357.1:c.1782+45A>G, XM_011543358.1:c.1722+45A>G, XM_011543359.1:c.1624-106A>G, rs17238505, rs17562582, rs386587624, rs56538861, rs59397732
A > G
SNP
No VIP available CA VA
rs3917643 NC_000001.10:g.95001867T>C, NC_000001.11:g.94536311T>C, NG_029366.1:g.10547A>G, NM_001178096.1:c.213-147A>G, NM_001993.4:c.213-147A>G, rs386589262
T > C
SNP
VIP No Clinical Annotations available No Variant Annotations available
rs4149015 NC_000012.11:g.21283322G>A, NC_000012.12:g.21130388G>A, NG_011745.1:g.4195G>A, NM_006446.4:c.-910G>A
G > A
SNP
rs4149056 NC_000012.11:g.21331549T>C, NC_000012.12:g.21178615T>C, NG_011745.1:g.52422T>C, NM_006446.4:c.521T>C, NP_006437.3:p.Val174Ala, rs52816141, rs60037639
T > C
SNP
V174A
No VIP available CA VA
rs4149081 NC_000012.11:g.21378021G>A, NC_000012.12:g.21225087G>A, NG_011745.1:g.98894G>A, NM_006446.4:c.1865+248G>A, rs60942524
G > A
SNP
No VIP available CA VA
rs4253728 NC_000022.10:g.46610067G>A, NC_000022.11:g.46214170G>A, NG_012204.1:g.68569G>A, NM_001001928.2:c.209-1003G>A, NM_005036.4:c.209-1003G>A, XM_005261653.1:c.209-1003G>A, XM_005261654.1:c.209-1003G>A, XM_005261655.1:c.209-1003G>A, XM_005261655.2:c.209-1003G>A, XM_005261656.1:c.209-1003G>A, XM_005261656.2:c.209-1003G>A, XM_005261657.1:c.209-1003G>A, XM_005261658.1:c.209-1003G>A, XM_006724269.2:c.209-1003G>A, XM_006724270.2:c.209-1003G>A, XM_011530239.1:c.209-1003G>A, XM_011530240.1:c.209-1003G>A, XM_011530241.1:c.209-1003G>A, XM_011530242.1:c.209-1003G>A, XM_011530243.1:c.209-1003G>A, XM_011530244.1:c.-198-1003G>A, XM_011530245.1:c.-198-1003G>A, XR_244379.1:n.432-1003G>A, XR_937869.1:n.524-1003G>A, XR_937870.1:n.523-1003G>A, rs17242080, rs56473198, rs56722050
G > A
SNP
No VIP available CA VA
rs4363657 NC_000012.11:g.21368722T>C, NC_000012.12:g.21215788T>C, NG_011745.1:g.89595T>C, NM_006446.4:c.1498-1331T>C, rs59042670
T > C
SNP
No VIP available CA VA
rs4673 NC_000016.10:g.88646828A>G, NC_000016.9:g.88713236A>G, NG_007291.1:g.9222T>C, NM_000101.2:c.214T>C, NM_000101.3:c.214T>C, NP_000092.2:p.Tyr72His, XM_011522905.1:c.214T>C, XP_011521207.1:p.Tyr72His, rs11266997, rs1130413, rs2228471, rs2242272, rs3189211, rs386594564, rs4782392, rs59455247
A > G
SNP
Y72H
No VIP available No Clinical Annotations available VA
rs4693075 NC_000004.11:g.84192168G>C, NC_000004.12:g.83271015G>C, NG_015825.1:g.18900C>G, NM_015697.7:c.779-1022C>G, XM_005262926.1:c.425-1022C>G, XM_005262927.1:c.299-1022C>G, XM_011531855.1:c.779-1022C>G, XM_011531856.1:c.779-1022C>G, XM_011531857.1:c.779-1022C>G, XM_011531858.1:c.779-1022C>G, XM_011531859.1:c.779-1022C>G, XM_011531860.1:c.779-1022C>G, XM_011531861.1:c.779-1022C>G, XM_011531862.1:c.779-1022C>G, XM_011531863.1:c.779-1022C>G, XM_011531864.1:c.779-1022C>G, XM_011531865.1:c.779-1022C>G, XM_011531866.1:c.779-1022C>G, XM_011531867.1:c.425-1022C>G, XR_427543.2:n.938-1022C>G, XR_938721.1:n.949-1022C>G, rs58141687
G > C
SNP
No VIP available CA VA
rs4823613 NC_000022.10:g.46598307A>G, NC_000022.11:g.46202410A>G, NG_012204.1:g.56809A>G, NM_001001928.2:c.208+3819A>G, NM_005036.4:c.208+3819A>G, XM_005261653.1:c.208+3819A>G, XM_005261654.1:c.208+3819A>G, XM_005261655.1:c.208+3819A>G, XM_005261655.2:c.208+3819A>G, XM_005261656.1:c.208+3819A>G, XM_005261656.2:c.208+3819A>G, XM_005261657.1:c.208+3819A>G, XM_005261658.1:c.208+3819A>G, XM_006724269.2:c.208+3819A>G, XM_006724270.2:c.208+3819A>G, XM_011530239.1:c.208+3819A>G, XM_011530240.1:c.208+3819A>G, XM_011530241.1:c.208+3819A>G, XM_011530242.1:c.208+3819A>G, XM_011530243.1:c.208+3819A>G, XM_011530244.1:c.-199+3819A>G, XM_011530245.1:c.-199+3819A>G, XR_244379.1:n.431+3819A>G, XR_937869.1:n.523+3819A>G, XR_937870.1:n.522+3819A>G, rs5767571, rs58091507, rs74281148
A > G
SNP
No VIP available No Clinical Annotations available VA
rs539748 NC_000023.10:g.113821349T=, NC_000023.10:g.113821349T>C, NC_000023.11:g.114586876C>T, NG_012082.2:g.7792C=, NG_012082.2:g.7792C>T, NM_000868.3:c.-147+2217C>T, NM_000868.3:c.-147+2217T>C, NM_001256760.2:c.-238+2217C>T, NM_001256760.2:c.-238+2217T>C, NM_001256761.2:c.-147+2217C>T, NM_001256761.2:c.-147+2217T>C, NW_004070891.1:g.255678C=, NW_004070891.1:g.255678C>T, rs17260551, rs56834670
T > C
SNP
No VIP available CA VA
rs5882 NC_000016.10:g.56982180G>A, NC_000016.9:g.57016092G>A, NG_008952.1:g.25258G>A, NM_000078.2:c.1264G>A, NM_001286085.1:c.1084G>A, NP_000069.2:p.Val422Ile, NP_001273014.1:p.Val362Ile, XM_005255776.1:c.1084G>A, XP_005255833.1:p.Val362Ile, rs1131843, rs12720881, rs1613122, rs17231896, rs17414131, rs17845778, rs17858738, rs1801707, rs289738, rs3192075, rs61212082
G > A
SNP
V422I
No VIP available No Clinical Annotations available VA
rs60282872 NC_000017.10:g.17740165delC, NG_029029.1:g.5161delG, NM_001005291.2:c.-34delG, NM_004176.4:c.-34delG, XM_005256772.1:c.-34delG, rs143925746, rs368516250
C > -
indel
No VIP available No Clinical Annotations available VA
rs6312 NC_000013.10:g.47470824C>T, NC_000013.11:g.46896689C>T, NG_013011.1:g.5346G>A, NM_000621.4:c.-344G>A, NM_001165947.2:c.145G>A, NP_001159419.1:p.Asp49Asn, rs17289199, rs36212450, rs60357050
C > T
SNP
D49N
No VIP available No Clinical Annotations available VA
rs6318 NC_000023.10:g.113965735G=, NC_000023.10:g.113965735G>C, NC_000023.11:g.114731326C=, NC_000023.11:g.114731326C>G, NG_012082.2:g.152242G=, NG_012082.2:g.152242G>C, NM_000868.3:c.68G=, NM_000868.3:c.68G>C, NM_001256760.2:c.68G=, NM_001256760.2:c.68G>C, NM_001256761.2:c.68G=, NM_001256761.2:c.68G>C, NP_000859.1:p.Cys23=, NP_000859.1:p.Cys23Ser, NP_001243689.1:p.Cys23=, NP_001243689.1:p.Cys23Ser, NP_001243690.1:p.Cys23=, NP_001243690.1:p.Cys23Ser, NW_004070891.1:g.400128C=, NW_004070891.1:g.400128C>G, XR_944300.1:n.209-550C>G, XR_944300.1:n.209-550G>C, XR_944301.1:n.209-550C>G, XR_944301.1:n.209-550G>C
G > C
SNP
C23S
No VIP available No Clinical Annotations available VA
rs659734 NC_000013.10:g.47435283G>A, NC_000013.11:g.46861148G>A, NG_013011.1:g.40887C>T, NM_000621.4:c.614-25509C>T, NM_001165947.2:c.362-25509C>T, rs17359936, rs386603779, rs59168055
G > A
SNP
No VIP available CA VA
rs662 NC_000007.13:g.94937446T>C, NC_000007.14:g.95308134T>C, NG_008779.1:g.21439A>G, NM_000446.5:c.575A>G, NP_000437.3:p.Gln192Arg, rs11567868, rs13306697, rs17773773, rs386603940, rs60480675
T > C
SNP
Q192R
No VIP available CA VA
rs662799 NC_000011.10:g.116792991G>A, NC_000011.9:g.116663707G>A, NG_015894.1:g.4430C>T, NM_001166598.1:c.-620C>T, NM_052968.4:c.-644C>T, rs3809039, rs60708336
G > A
SNP
No VIP available No Clinical Annotations available VA
rs676643 NC_000001.10:g.23521340G>A, NC_000001.11:g.23194847G>A, NM_000864.4:c.-628C>T, rs3753253, rs386604973, rs61725275
G > A
SNP
No VIP available CA No Variant Annotations available
rs6924995 NC_000006.11:g.16161425A>G, NC_000006.12:g.16161194A>G, NG_009456.1:g.361A>G, rs59613901
A > G
SNP
No VIP available CA VA
rs705379 NC_000007.13:g.94953895G>A, NC_000007.14:g.95324583G>A, NG_008779.1:g.4990C>T, NM_000446.5:c.-108C>T, rs11567858, rs58244060
G > A
SNP
No VIP available CA VA
rs708272 NC_000016.10:g.56962376G>A, NC_000016.9:g.56996288G>A, NG_008952.1:g.5454G>A, NM_000078.2:c.118+279G>A, NM_001286085.1:c.118+279G>A, XM_005255776.1:c.118+279G>A, XM_006721124.2:c.118+279G>A, rs17237904, rs17290342, rs57207652
G > A
SNP
No VIP available CA VA
rs717620 NC_000010.10:g.101542578C>T, NC_000010.11:g.99782821C>T, NG_011798.1:g.5116C>T, NM_000392.4:c.-24C>T, XM_005269536.1:c.-24C>T, XM_006717631.2:c.-24C>T, XM_011539291.1:c.-24C>T, XR_945604.1:n.166C>T, XR_945605.1:n.168C>T, rs17216163, rs386485129, rs58371376
C > T
SNP
No VIP available No Clinical Annotations available VA
rs7412 NC_000019.10:g.44908822C>T, NC_000019.9:g.45412079C>T, NG_007084.2:g.8041C>T, NM_000041.3:c.526C>T, NM_001302688.1:c.604C>T, NM_001302689.1:c.526C>T, NM_001302690.1:c.526C>T, NM_001302691.1:c.526C>T, NP_000032.1:p.Arg176Cys, NP_001289617.1:p.Arg202Cys, NP_001289618.1:p.Arg176Cys, NP_001289619.1:p.Arg176Cys, NP_001289620.1:p.Arg176Cys, XM_005258867.1:c.604C>T, XM_005258868.1:c.526C>T, XP_005258924.1:p.Arg202Cys, XP_005258925.1:p.Arg176Cys, rs3200542
C > T
SNP
R176C
rs776746 NC_000007.13:g.99270539C>T, NC_000007.14:g.99672916T>C, NG_007938.1:g.12083G=, NG_007938.1:g.12083G>A, NM_000777.4:c.219-237A>G, NM_000777.4:c.219-237G>A, NM_001190484.2:c.219-237A>G, NM_001190484.2:c.219-237G>A, NM_001291829.1:c.-253-1A>G, NM_001291829.1:c.-253-1G>A, NM_001291830.1:c.189-237A>G, NM_001291830.1:c.189-237G>A, NR_033807.2:n.717-1A>G, NR_033807.2:n.717-1G>A, NR_033808.1:n.689-1G>A, NR_033809.1:n.581-237G>A, NR_033810.1:n.689-1G>A, NR_033811.1:n.321-1G>A, NR_033812.1:n.321-1G>A, XM_005250169.1:c.189-237G>A, XM_005250170.1:c.-357-1G>A, XM_005250171.1:c.-253-1G>A, XM_005250172.1:c.-254G>A, XM_005250173.1:c.-331-237G>A, XM_005250198.1:c.806-4288C>T, XM_006715859.2:c.219-237A>G, XM_011515843.1:c.-254A>G, XM_011515844.1:c.-229-237A>G, XM_011515845.1:c.-463-1A>G, XM_011515846.1:c.-331-237A>G, XM_011515847.1:c.-571-1A>G, XR_927383.1:n.344-237A>G, XR_927402.1:n.1466+48736T>C, rs10361242, rs11266830, rs386613022, rs58244770
C > T
SNP
No VIP available No Clinical Annotations available VA
rs8014194 NC_000014.8:g.95720678T>A, NC_000014.9:g.95254341T>A, NM_024734.3:c.83-24208A>T, XM_005268064.1:c.83-24208A>T, XM_005268065.1:c.83-24208A>T, XM_011537158.1:c.83-24208A>T, XM_011537159.1:c.83-24208A>T, XR_245721.1:n.195-24208A>T, XR_245721.2:n.195-24208A>T, XR_245722.1:n.195-24208A>T, XR_429330.2:n.195-24208A>T, XR_429332.2:n.195-24208A>T, rs57153875
T > A
SNP
No VIP available CA VA
rs9806699 NC_000015.10:g.45448194G>A, NC_000015.9:g.45740392G>A, XM_011522289.1:c.-478G>A, rs58677873
G > A
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • Simvastatin [Usan:Ban:Inn]
  • Simvastatina [Spanish]
  • Simvastatine [French]
  • Simvastatinum [Latin]
Trade Names
  • Cholestat
  • Coledis
  • Colemin
  • Corolin
  • Denan
  • Labistatin
  • Lipex
  • Lodales
  • Medipo
  • Nivelipol
  • Pantok
  • Rendapid
  • Simovil
  • Sinvacor
  • Sivastin
  • Synvinolin
  • Vasotenal
  • Vytorin
  • Zocor
  • Zocord
Brand Mixture Names
  • Inegy (Simvastatin + Ezetimibe)

PharmGKB Accession Id

PA451363

Type(s):

Drug

Description

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.

Source: Drug Bank

Indication

For the treatment of hypercholesterolemia.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol.

Source: Drug Bank

Pharmacology

Simvastatin, the methylated form of lovastatin, is an oral antilipemic agent which inhibits HMG-CoA reductase. simvastatin is used in the treatment of primary hypercholesterolemia and is effective in reducing total and LDL-cholesterol as well as plasma triglycerides and apolipoprotein B.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Avoid taking with grapefruit juice.|Avoid drastic changes in dietary habit.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic, simvastatin is a substrate for CYP3A4.

Source: Drug Bank

Protein Binding

Both simvastatin and its b-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins.

Source: Drug Bank

Absorption

Absorption of simvastatin, estimated relative to an intravenous reference dose, in each of two animal species tested, averaged about 85% of an oral dose. In animal studies, after oral dosing, simvastatin achieved substantially higher concentrations in the liver than in non-target tissues.

Source: Drug Bank

Half-Life

3 hours

Source: Drug Bank

Route of Elimination

Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces.

Source: Drug Bank

Chemical Properties

Chemical Formula

C25H38O5

Source: Drug Bank

Isomeric SMILES

CCC(C)(C)C(=O)O[C@H]1C[C@H](C=C2[C@H]1[C@H]([C@H](C=C2)C)CC[C@@H]3C[C@H](CC(=O)O3)O)C

Source: OpenEye

Canonical SMILES

[H][C@]

Source: Drug Bank

Average Molecular Weight

418.5662

Source: Drug Bank

Monoisotopic Molecular Weight

418.271924326

Source: Drug Bank

SMILES

[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)C(C)(C)CC

Source: Drug Bank

InChI String

InChI=1S/C25H38O5/c1-6-25(4,5)24(28)30-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-19-13-18(26)14-22(27)29-19/h7-8,11,15-16,18-21,23,26H,6,9-10,12-14H2,1-5H3/t15-,16-,18+,19+,20-,21-,23-/m0/s1

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics
    Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
AGT (source: Drug Bank)
BMP2 (source: Drug Bank)
CASP3 (source: Drug Bank)
CCL2 (source: Drug Bank)
CD40 (source: Drug Bank)
COL13A1 (source: Drug Bank)
CXCL8 (source: Drug Bank)
F2 (source: Drug Bank)
HMGCR (source: Drug Bank)
ICAM1 (source: Drug Bank)
IFNG (source: Drug Bank)
IL6 (source: Drug Bank)
ITGB2 (source: Drug Bank)
LTB (source: Drug Bank)
MAPK3 (source: Drug Bank)
MMP3 (source: Drug Bank)
MMP9 (source: Drug Bank)
PPARA (source: Drug Bank)
RAC1 (source: Drug Bank)
RHOA (source: Drug Bank)
SERPINE1 (source: Drug Bank)
TNF (source: Drug Bank)
VEGFA (source: Drug Bank)

Drug Interactions

Interaction Description
amiodarone - simvastatin Increased risk of rhabdomyolysis (source: Drug Bank)
amiodarone - simvastatin Increased risk of rhabdomyolysis (source: Drug Bank)
amprenavir - simvastatin Amprenavir can possibly increase the statin toxicity (source: Drug Bank)
amprenavir - simvastatin Amprenavir can possibly increase the statin toxicity (source: Drug Bank)
atazanavir - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
atazanavir - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
bosentan - simvastatin Bosentan could decrease the statin effect (source: Drug Bank)
bosentan - simvastatin Bosentan could decrease the statin effect (source: Drug Bank)
carbamazepine - simvastatin Decreases the effect of the statin (source: Drug Bank)
carbamazepine - simvastatin Decreases the effect of the statin (source: Drug Bank)
clarithromycin - simvastatin The macrolide possibly increases the statin toxicity (source: Drug Bank)
clarithromycin - simvastatin The macrolide, clarithromycin, may increase the toxicity of the statin, simvastatin. (source: Drug Bank)
colchicine - simvastatin Increased risk of rhabdomyolysis with this combination (source: Drug Bank)
colchicine - simvastatin Increased risk of rhabdomyolysis with this combination (source: Drug Bank)
cyclosporine - simvastatin Possible myopathy and rhabdomyolysis (source: Drug Bank)
cyclosporine - simvastatin Possible myopathy and rhabdomyolysis (source: Drug Bank)
delavirdine - simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
delavirdine - simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
diltiazem - simvastatin Increases the effect and toicity of simvastatin (source: Drug Bank)
diltiazem - simvastatin Increases the effect and toicity of simvastatin (source: Drug Bank)
erythromycin - simvastatin The macrolide possibly increases the statin toxicity (source: Drug Bank)
erythromycin - simvastatin The macrolide, erythromycin, may increase the toxicity of the statin, simvastatin. (source: Drug Bank)
fenofibrate - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
fenofibrate - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
fluconazole - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
fluconazole - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
fosamprenavir - simvastatin Amprenavir can possibly increase the statin toxicity (source: Drug Bank)
fosamprenavir - simvastatin Amprenavir can possibly increase the statin toxicity (source: Drug Bank)
fusidic acid - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
gemfibrozil - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
gemfibrozil - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
imatinib - simvastatin Imatinib increases the effect and toxicity of statin (source: Drug Bank)
imatinib - simvastatin Imatinib increases the effect and toxicity of statin (source: Drug Bank)
itraconazole - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
itraconazole - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
itraconazole - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
ketoconazole - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
ketoconazole - simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
nefazodone - simvastatin Nefazodone increases the effect and toxicity of the statin drug (source: Drug Bank)
nefazodone - simvastatin Nefazodone increases the effect and toxicity of the statin drug (source: Drug Bank)
nelfinavir - simvastatin Nelfinavir increases the effect and toxicity of the statin (source: Drug Bank)
nelfinavir - simvastatin Nelfinavir increases the effect and toxicity of the statin (source: Drug Bank)
nevirapine - simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
nevirapine - simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
quinupristin - simvastatin This combination presents an increased risk of toxicity (source: Drug Bank)
ranolazine - simvastatin Ranolazine increases the statin level (source: Drug Bank)
rifabutin - simvastatin The rifamycin decreases the effect of the statin drug (source: Drug Bank)
rifabutin - simvastatin The rifamycin decreases the effect of the statin drug (source: Drug Bank)
rifampin - simvastatin The rifamycin decreases the effect of the statin drug (source: Drug Bank)
rifampin - simvastatin The rifamycin decreases the effect of the statin drug (source: Drug Bank)
telithromycin - simvastatin Telithromycin may possibly increase statin toxicity (source: Drug Bank)
telithromycin - simvastatin Telithromycin may reduce clearance of Simvastatin. Concomitant therapy is contraindicated. (source: Drug Bank)
tipranavir - simvastatin Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Simvastatin. Concomitant therapy is contraindicated. (source: Drug Bank)
verapamil - simvastatin Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Simvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce Simvastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Simvastatin if Verapamil is initiated, discontinued or dose changed. (source: Drug Bank)
voriconazole - simvastatin Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastain if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
May Prevent
Contraindicated With

Publications related to simvastatin: 128

No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
RP1-13D10.2 Is a Novel Modulator of Statin-Induced Changes in Cholesterol. Circulation. Cardiovascular genetics. 2016. Mitchel Katrina, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Impact of CYP2D6, CYP3A5, CYP2C19, CYP2A6, SLCO1B1, ABCB1, and ABCG2 gene polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid. Pharmacogenetics and genomics. 2015. Choi Hee Youn, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Individual and Combined Associations of Genetic Variants in CYP3A4, CYP3A5, and SLCO1B1 With Simvastatin and Simvastatin Acid Plasma Concentrations. Journal of cardiovascular pharmacology. 2015. Luzum Jasmine A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between polymorphism within the RYR2 receptor and development of statin-associated myalgia/myopathy in the Czech population. European journal of internal medicine. 2015. Hubacek Jaroslav A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evidence for Clinical Implementation of Pharmacogenomics in Cardiac Drugs. Mayo Clinic proceedings. 2015. Kaufman Amy L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Development and Application of a Mechanistic Pharmacokinetic Model for Simvastatin and its Active Metabolite Simvastatin Acid Using an Integrated Population PBPK Approach. Pharmaceutical research. 2015. Tsamandouras Nikolaos, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification and mechanistic investigation of drug-drug interactions associated with myopathy - A translational approach. Clinical pharmacology and therapeutics. 2015. Han Xu, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
GATM polymorphism associated with the risk for statin-induced myopathy does not replicate in case-control analysis of 715 dyslipidemic individuals. Cell metabolism. 2015. Luzum Jasmine A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A multicenter phase I study of pazopanib in combination with paclitaxel in first-line treatment of patients with advanced solid tumors. Molecular cancer therapeutics. 2015. Kendra Kari L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Function-impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify the therapeutic efficacy of statins in a population-based cohort. Pharmacogenetics and genomics. 2014. Meyer Zu Schwabedissen Henriette E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetic variation in the UGT1A locus is associated with simvastatin efficacy in a clinical practice setting. Pharmacogenomics. 2014. Iwuchukwu Otito F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Mechanisms and assessment of statin-related muscular adverse effects. British journal of clinical pharmacology. 2014. Moßhammer Dirk, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A polymorphism in HLA-G modifies statin benefit in asthma. The pharmacogenomics journal. 2014. Naidoo D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Ancestry and other genetic associations with plasma PCSK9 response to simvastatin. Pharmacogenetics and genomics. 2014. Theusch Elizabeth, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
CYP3A4*22 and CYP3A5*3 are associated with increased levels of plasma simvastatin concentrations in the cholesterol and pharmacogenetics study cohort. Pharmacogenetics and genomics. 2014. Kitzmiller Joseph P, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Identification of the effect of multiple polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid using a population-modeling approach. Clinical pharmacology and therapeutics. 2014. Tsamandouras N, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clinical pharmacology and therapeutics. 2014. Ramsey Laura B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Adoption of a clinical pharmacogenomics implementation program during outpatient care-initial results of the University of Chicago "1,200 Patients Project". American journal of medical genetics. Part C, Seminars in medical genetics. 2014. O'Donnell Peter H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clinical pharmacology and therapeutics. 2013. Van Driest Sara L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
The SLCO1B1 c.521T>C polymorphism is associated with dose decrease or switching during statin therapy in the Rotterdam Study. Pharmacogenetics and genomics. 2013. de Keyser Catherine E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Applied Pharmacogenomics in Cardiovascular Medicine. Annual review of medicine. 2013. Weeke Peter, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Characterization of Statin Dose-response within Electronic Medical Records. Clinical pharmacology and therapeutics. 2013. Wei Wei-Qi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Statin induced changes in gene expression in EBV-transformed and native B-cells. Human molecular genetics. 2013. Bolotin Eugene, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
SLCO1B1 Genetic Variant Associated With Statin-Induced Myopathy: A Proof of Concept Study Using the Clinical Practice Research Datalink (CPRD). Clinical pharmacology and therapeutics. 2013. Carr Daniel F, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A statin-dependent QTL for GATM expression is associated with statin-induced myopathy. Nature. 2013. Mangravite Lara M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetic variation in the PPARA gene is associated with simvastatin-mediated cholesterol reduction in the Rotterdam Study. Pharmacogenomics. 2013. de Keyser Catherine E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
International transporter consortium commentary on clinically important transporter polymorphisms. Clinical pharmacology and therapeutics. 2013. Giacomini K M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Lack of association between SLCO1B1 polymorphisms and clinical myalgia following rosuvastatin therapy. American heart journal. 2013. Danik Jacqueline S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Lack of association between SLCO1B1 polymorphism and the lipid-lowering effects of atorvastatin and simvastatin in Chinese individuals. European journal of clinical pharmacology. 2013. Fu Qiang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A4/5 combined genotype analysis for predicting statin dose requirement for optimal lipid control. Drug metabolism and drug interactions. 2013. Kitzmiller Joseph Paul, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Amlodipine - Not a Significant Contributor to Clopidogrel Non-Response?. Heart (British Cardiac Society). 2013. Kreutz Rolf P, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Associations between the genotypes and phenotype of CYP3A and the lipid response to simvastatin in Chinese patients with hypercholesterolemia. Pharmacogenomics. 2013. Hu Miao, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A4*22: promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy. Pharmacogenomics. 2013. Elens Laure, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Correction: Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment. PloS one. 2013. Kaddurah-Daouk Rima, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Levels of cholesterol in small LDL particles predict atherosclerosis progression and incident CHD in the HDL-Atherosclerosis Treatment Study (HATS). PloS one. 2013. Williams Paul T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics in clinical practice and drug development. Nature biotechnology. 2012. Harper Andrew R, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
RHOA Is a Modulator of the Cholesterol-Lowering Effects of Statin. PLoS genetics. 2012. Medina Marisa W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Concomitant use of pazopanib and simvastatin increases the risk of transaminase elevations in patients with cancer. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2012. Xu C F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Literature based drug interaction prediction with clinical assessment using electronic medical records: novel myopathy associated drug interactions. PLoS computational biology. 2012. Duke Jon D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenetics and genomics. 2012. Lamba Jatinder, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Intronic variants in SLCO1B1 related to statin-induced myopathy are associated with the low-density lipoprotein cholesterol response to statins in Chinese patients with hyperlipidaemia. Pharmacogenetics and genomics. 2012. Hu Miao, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The Clinical Pharmacogenomics Implementation Consortium: CPIC Guideline for SLCO1B1 and Simvastatin-Induced Myopathy. Clinical pharmacology and therapeutics. 2012. Wilke R A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A clinically significant interaction between warfarin and simvastatin is unique to carriers of the CYP2C9*3 allele. Pharmacogenomics. 2012. Andersson Marine L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment. PloS one. 2012. Trupp Miles, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy. The pharmacogenomics journal. 2011. Becker M L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Novel CYP3A4 intron 6 single nucleotide polymorphism is associated with simvastatin-mediated cholesterol reduction in The Rotterdam Study. Pharmacogenetics and genomics. 2011. Elens Laure, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Disease-drug-drug interaction involving tocilizumab and simvastatin in patients with rheumatoid arthritis. Clinical pharmacology and therapeutics. 2011. Schmitt C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
No impact of KIF6 genotype on vascular risk and statin response among 18,348 randomized patients in the heart protection study. Journal of the American College of Cardiology. 2011. Hopewell Jemma C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics: the genetics of variable drug responses. Circulation. 2011. Roden Dan M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Transporter-Mediated Drug Uptake and Efflux: Important Determinants of Adverse Drug Reactions. Clinical pharmacology and therapeutics. 2011. Zolk O, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB: very important pharmacogene--HMGCR. Pharmacogenetics and genomics. 2011. Medina Marisa Wong, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin. The pharmacogenomics journal. 2011. Brunham L R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Enteric microbiome metabolites correlate with response to simvastatin treatment. PloS one. 2011. Kaddurah-Daouk Rima, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Effects of lipid-lowering drugs on reverse cholesterol transport gene expressions in peripheral blood mononuclear and HepG2 cells. Pharmacogenomics. 2010. Genvigir Fabiana Dalla Vecchia, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Combined influence of LDLR and HMGCR sequence variation on lipid-lowering response to simvastatin. Arteriosclerosis, thrombosis, and vascular biology. 2010. Mangravite Lara M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study. Metabolomics : Official journal of the Metabolomic Society. 2010. Kaddurah-Daouk Rima, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer. Cancer prevention research (Philadelphia, Pa.). 2010. Lipkin Steven M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influence of genetic variation in CYP3A4 and ABCB1 on dose decrease or switching during simvastatin and atorvastatin therapy. Pharmacoepidemiology and drug safety. 2010. Becker Matthijs L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A polymorphism in the VKORC1 regulator calumenin predicts higher warfarin dose requirements in African Americans. Clinical pharmacology and therapeutics. 2010. Voora D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic and clinical predictors of warfarin dose requirements in African Americans. Clinical pharmacology and therapeutics. 2010. Cavallari L H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics of membrane transporters: past, present and future. Pharmacogenomics. 2010. Yee Sook Wah, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. The pharmacogenomics journal. 2010. Wang D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenetics and genomics. 2010. Oshiro Connie, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Common sequence variants in pharmacodynamic and pharmacokinetic pathway-related genes conferring LDL cholesterol response to statins. Pharmacogenomics. 2010. Chien Kuo-Liong, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Transporter pharmacogenetics and statin toxicity. Clinical pharmacology and therapeutics. 2010. Niemi M. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genome-wide association of lipid-lowering response to statins in combined study populations. PloS one. 2010. Barber Mathew J, et al. PubMed
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Warfarin interactions with substances listed in drug information compendia and in the FDA-approved label for warfarin sodium. Clinical pharmacology and therapeutics. 2009. Anthony M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Anti-inflammatory effects of simvastatin on adipokines in type 2 diabetic patients with carotid atherosclerosis. Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease. 2009. Hu Yun, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The pharmacogenetics of statin therapy: when the body aches, the mind will follow. Journal of the American College of Cardiology. 2009. Rossi Joseph S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug discovery and natural products: end of an era or an endless frontier?. Science (New York, N.Y.). 2009. Li Jesse W-H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Statin regulation of CYP3A4 and CYP3A5 expression. Pharmacogenomics. 2009. Willrich Maria Alice Vieira, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Tissue factor +5466A>G polymorphism determines thrombin formation following vascular injury and thrombin-lowering effects of simvastatin in patients with ischemic heart disease. Atherosclerosis. 2009. Undas Anetta, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Impact of OATP transporters on pharmacokinetics. British journal of pharmacology. 2009. Kalliokoski A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Medicinal Chemistry of Drugs used in Diabetic Cardiomyopathy. Current medicinal chemistry. 2009. Adeghate E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
The 223A>G polymorphism of the leptin receptor gene and lipid-lowering efficacy of simvastatin in Chinese patients with coronary heart disease. European journal of clinical pharmacology. 2009. Sun Yan-Ming, et al. PubMed
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The SLCO1B1*5 genetic variant is associated with statin-induced side effects. Journal of the American College of Cardiology. 2009. Voora Deepak, et al. PubMed
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Common genetic variation in the ABCB1 gene is associated with the cholesterol-lowering effect of simvastatin in males. Pharmacogenomics. 2009. Becker Matthijs L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Different effects of the ABCG2 c.421C>A SNP on the pharmacokinetics of fluvastatin, pravastatin and simvastatin. Pharmacogenomics. 2009. Keskitalo Jenni E, et al. PubMed
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Impact of apolipoprotein A5 variants on statin treatment efficacy. Pharmacogenomics. 2009. Hubacek Jaroslav A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The role of HMGCR alternative splicing in statin efficacy. Trends in cardiovascular medicine. 2009. Medina Marisa Wong, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Data-driven methods to discover molecular determinants of serious adverse drug events. Clinical pharmacology and therapeutics. 2009. Chiang A P, et al. PubMed
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A paucimorphic variant in the HMG-CoA reductase gene is associated with lipid-lowering response to statin treatment in diabetes: a GoDARTS study. Pharmacogenetics and genomics. 2008. Donnelly Louise A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Effect of atorvastatin on paraoxonase1 (PON1) and oxidative status. Pharmacological reports : PR. 2009. Nagila Amar, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genetic variation at the LDL receptor and HMG-CoA reductase gene loci, lipid levels, statin response, and cardiovascular disease incidence in PROSPER. Atherosclerosis. 2008. Polisecki Eliana, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Association between a frequent allele of the gene encoding OATP1B1 and enhanced LDL-lowering response to fluvastatin therapy. Pharmacogenomics. 2008. Couvert Philippe, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Machine learning methods and docking for predicting human pregnane X receptor activation. Chemical research in toxicology. 2008. Khandelwal Akash, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1 alpha are associated with C-reactive protein. American journal of human genetics. 2008. Reiner Alexander P, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Alternative splicing of 3-hydroxy-3-methylglutaryl coenzyme A reductase is associated with plasma low-density lipoprotein cholesterol response to simvastatin. Circulation. 2008. Medina Marisa Wong, et al. PubMed
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Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is associated with racial differences in low-density lipoprotein cholesterol response to simvastatin treatment. Circulation. 2008. Krauss Ronald M, et al. PubMed
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Pharmacogenetic predictors of statin-mediated low-density lipoprotein cholesterol reduction and dose response. Circulation. Cardiovascular genetics. 2008. Voora Deepak, et al. PubMed
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Effect of statin therapy on plasma high-density lipoprotein-cholesterol levels is modified by paraoxonase 1 in Chinese patients with coronary heart disease. Clinical and experimental pharmacology & physiology. 2008. Fu Ran, et al. PubMed
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ABCB1 haplotypes differentially affect the pharmacokinetics of the acid and lactone forms of simvastatin and atorvastatin. Clinical pharmacology and therapeutics. 2008. Keskitalo J E, et al. PubMed
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CYP3A4*1G polymorphism is associated with lipid-lowering efficacy of atorvastatin but not of simvastatin. European journal of clinical pharmacology. 2008. Gao Yuan, et al. PubMed
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Polymorphism of the hepatic influx transporter organic anion transporting polypeptide 1B1 is associated with increased cholesterol synthesis rate. Pharmacogenetics and genomics. 2008. Pasanen Marja K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Statins inhibit toll-like receptor 4-mediated lipopolysaccharide signaling and cytokine expression. Pharmacogenetics and genomics. 2008. Hodgkinson Conrad P, et al. PubMed
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SLCO1B1 variants and statin-induced myopathy--a genomewide study. The New England journal of medicine. 2008. SEARCH Collaborative Group, et al. PubMed
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Simvastatin with or without ezetimibe in familial hypercholesterolemia. The New England journal of medicine. 2008. Kastelein John J P, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genetic analysis of fluvastatin response and dyslipidemia in renal transplant recipients. Journal of lipid research. 2007. Singer Jonathan B, et al. PubMed
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Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia. Journal of atherosclerosis and thrombosis. 2007. Davis Harry R, et al. PubMed
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Pharmacogenetic study of cholesteryl ester transfer protein gene and simvastatin treatment in hypercholesterolaemic subjects. Expert opinion on pharmacotherapy. 2007. Anagnostopoulou Katherine, et al. PubMed
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Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. Journal of clinical pharmacology. 2007. Kim Kyoung-Ah, et al. PubMed
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Physiogenomic association of statin-related myalgia to serotonin receptors. Muscle & nerve. 2007. Ruaño Gualberto, et al. PubMed
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CYP2D6*4 polymorphism is associated with statin-induced muscle effects. Pharmacogenetics and genomics. 2007. Frudakis Tony N, et al. PubMed
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Tolerability of statins is not linked to CYP450 polymorphisms, but reduced CYP2D6 metabolism improves cholesteraemic response to simvastatin and fluvastatin. Pharmacological research : the official journal of the Italian Pharmacological Society. 2007. Zuccaro Piergiorgio, et al. PubMed
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Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. The Journal of pharmacology and experimental therapeutics. 2007. Faucette Stephanie R, et al. PubMed
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Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle & nerve. 2006. Vladutiu Georgirene D, et al. PubMed
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Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clinical pharmacology and therapeutics. 2006. Neuvonen Pertti J, et al. PubMed
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Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart. Clinical pharmacology and therapeutics. 2006. Grube Markus, et al. PubMed
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SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenetics and genomics. 2006. Pasanen Marja K, et al. PubMed
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A beneficial effect of simvastatin on DNA damage in 242T allele of the NADPH oxidase p22phox in hypercholesterolemic patients. Clinica chimica acta; international journal of clinical chemistry. 2005. Shin Min-Jeong, et al. PubMed
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The role of common variants of ABCB1, CYP3A4, and CYP3A5 genes in lipid-lowering efficacy and safety of simvastatin treatment. Clinical pharmacology and therapeutics. 2005. Fiegenbaum Marilu, et al. PubMed
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Ile118Val genetic polymorphism of CYP3A4 and its effects on lipid-lowering efficacy of simvastatin in Chinese hyperlipidemic patients. European journal of clinical pharmacology. 2005. Wang An, et al. PubMed
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TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular disease in statin-treated patients with familial hypercholesterolemia. European journal of human genetics : EJHG. 2005. Mohrschladt Martina F, et al. PubMed
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The dependence of serum interleukin-6 level on PPAR-alpha polymorphism in men with coronary atherosclerosis. European journal of internal medicine. 2005. Skoczynska Anna, et al. PubMed
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The effect of statin therapy on plasma high-density lipoprotein cholesterol levels is modified by paraoxonase-1 in patients with familial hypercholesterolaemia. Journal of internal medicine. 2005. Himbergen T M, et al. PubMed
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An association study of 43 SNPs in 16 candidate genes with atorvastatin response. The pharmacogenomics journal. 2005. Thompson J F, et al. PubMed
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Determinants of variable response to simvastatin treatment: the role of common variants of SCAP, SREBF-1a and SREBF-2 genes. The pharmacogenomics journal. 2005. Fiegenbaum M, et al. PubMed
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Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA : the journal of the American Medical Association. 2004. Chasman Daniel I, et al. PubMed
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Lipid-lowering response to statins is affected by CYP3A5 polymorphism. Pharmacogenetics. 2004. Kivistö Kari T, et al. PubMed
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The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6. British journal of clinical pharmacology. 2003. Prueksaritanont Thomayant, et al. PubMed
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Leptin receptor polymorphism is associated with serum lipid levels and impairment of cholesterol lowering effect by simvastatin in Japanese men. Diabetes research and clinical practice. 2003. Takahashi-Yasuno Akiko, et al. PubMed
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Anti-atherosclerotic effect of simvastatin depends on the presence of apolipoprotein E. Atherosclerosis. 2002. Wang Yi Xin, et al. PubMed
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Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharmaceutics & drug disposition. 2000. Cohen L H, et al. PubMed
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The apolipoprotein epsilon4 allele determines prognosis and the effect on prognosis of simvastatin in survivors of myocardial infarction : a substudy of the Scandinavian simvastatin survival study. Circulation. 2000. Gerdes L U, et al. PubMed
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A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. The Journal of biological chemistry. 1999. Hsiang B, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
16714-681-01
DrugBank:
DB00641
PDB:
SIM
ChEBI:
9150
KEGG Drug:
D00434
PubChem Compound:
54454
PubChem Substance:
7847500
Drugs Product Database (DPD):
2253747
HET:
SIM
Therapeutic Targets Database:
DAP001519
FDA Drug Label at DailyMed:
0376351b-f1a0-43e5-a0b4-533072c49f39

Clinical Trials

These are trials that mention simvastatin and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, PubChem.