Drug/Small Molecule:
simvastatin

last updated 05/23/2012

CPIC Dosing 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

Guidelines regarding the use of pharmacogenomic tests in dosing for simvastatin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

Download: article and supplement

Excerpt from the simvastatin dosing guidelines:

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. Our recommended approach (Table 2 and Figure 1) begins with product-label changes recently implemented by the FDA. (The agency's recommendations are further summarized in Supplementary Table S1 online.) Decision-support tools are already being used to direct providers away from initiating the 80-mg simvastatin dose. At many of our institutions, SLCO1B1 genotype is further used to underscore this warning (i.e., myopathy risk for 80 mg of simvastatin) for subjects with a C allele at rs4149056 (see details in Supplementary Material).

The table below summarizes the therapeutic CPIC guidelines for simvastatin based on SLCO1B1 genotypes. These guidelines have been limited to the SLCO1B1*5 allele (rs4149056). At lower simvastatin doses (e.g., 40 mg daily), it is our position that this information should be used to warn providers about modest increases in myopathy risk for subjects with a C allele at rs4149056 (Figure 1). Under these circumstances, we also highlight the potential utility of routine creatine kinase (CK) surveillance (Table 2). If subjects with a C allele at rs4149056 do not achieve optimal low-density lipoprotein cholesterol-lowering efficacy with a lower dose of simvastatin, we recommend that the prescribing physician consider an alternative statin based on (i) potency differences, (ii) kinetic differences, (iii) comedications, (iv) hepatic function, (v) renal function, and (vi) relevant comorbidities.

Dosing recommendations for simvastatin, when rs4149056 genotype (or phenotype) is available (Table 2):

At the time of the development of this recommendation, there are no data available on the possible role of SLCO1B1 in simvastatin-induced myopathies in pediatric patient populations; however, there is no reason to suspect that SLCO1B1 variant alleles would affect simvastatin hepatic uptake differently in children compared to adults. Please see below for full details of these guidelines, with supporting evidence and disclaimers.

Genotype at rs4149056 Anticipated phenotype Implications for simvastatin Therapeutic recommendations Classification of recommendations
TT Normal activity Normal myopathy risk FDA recommends against 80 mg (unless already tolerated 12 months). Prescribe desired starting dose and adjust doses of simvastatin based on disease-specific guidelines. Strong
TC Intermediate activity Intermediate myopathy risk FDA recommends against 80 mg. Consider a lower dose; if suboptimal efficacy, consider an alternative statin. Strong
CC Low activity High myopathy risk FDA recommends against 80 mg. Prescribe a lower dose or consider an alternative statin; consider routine creatine kinase (CK) surveillance. Strong



Figure 1: PREDICT (Pharmacogenomics Resource for Enhanced Decisions in Clinical Care and Treatment) decision support algorithm for simvastatin. CK, creatine kinase.


PharmGKB contains no drug labels with pharmacogenomic information for this drug/small molecule. To report a drug label with PGx, click here.

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.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
DMET Plus (Affymetrix, Inc) Variant in SLCO1B1
VeraCode ADME Core Panel (Illumina, Inc) Variant in SLCO1B1
QPS SLCO1B1 SLCO1B1*15, SLCO1B1*1B, SLCO1B1*5 , rs2306283 , rs4149056

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.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? 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 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 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 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
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
No VIP available CA No Variant Annotations available
rs1057910 1075A>C, 47545517A>C, 47639A>C, 96741053A>C, CYP2C9*3, CYP2C9*3:Ile359Leu, CYP2C9: I359L, CYP2C9:359Ile>Leu, CYP2C9:Ile359Leu, Ile359Leu, mRNA 11A>C
A > C
Missense
Ile359Leu
No VIP available No Clinical Annotations available VA
rs1128503 1236T>C, 167964T>C, 25212444A>G, 87179601A>G, ABCB1 1236C>T, ABCB1*8, ABCB1: c.1236T>C, ABCB1:1236C>T, ABCB1:1236T>C, Gly412=, Gly412Gly, mRNA 1654T>C, p.Gly412Gly
A > G
Synonymous
Gly412Gly
No VIP available CA VA
rs1137101 177266A>G, 36030431A>G, 66058513A>G, 668A>G, Gln223Arg
A > G
Missense
Gln223Arg
No VIP available No Clinical Annotations available VA
rs1150226 -256A>G, -489A>G, 113845541A>G, 17407957A>G, 4745A>G
A > G
5' Flanking
No VIP available No Clinical Annotations available VA
rs11807862 2757900T>A, 298527T>A, 3279268T>A, 439-22448T>A
T > A
Intronic
No VIP available CA VA
rs12003906 107645477G>C, 107645477G>T, 303-39C>A, 303-39C>G, 36810009G>C, 36810009G>T, 49960C>A, 49960C>G
G > T
G > C
Intronic
No VIP available CA VA
rs12487736 2392G>A, 47399679C>T, 47459679C>T, Val798Ile
C > T
Missense
Val798Ile
No VIP available CA VA
rs1346268 16463586T>C, 2952A>G, 45673029T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs140700 24566G>A, 28543389C>T, 3280383C>T, 838-155G>A
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs1440451 154868879G>C, 498245G>C, 741+5529G>C
G > C
Intronic
No VIP available CA VA
rs1719247 16411542C>T, 45620985C>T
C > T
Not Available
rs17238540 2298+117T>G, 2457+117T>G, 25249857T>G, 27506T>G, 74655498T>G, HMGCR:SNP 29
T > G
Intronic
No VIP available CA VA
rs17244841 14863A>T, 25237214A>T, 451-174A>T, 74642855A>T, HMGCR:SNP 12
A > T
Intronic
No VIP available No Clinical Annotations available VA
rs1800588 -557C>T, 29514232C>T, 4501C>T, 58723675C>T
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs1805054 19992513C>T, 267C>T, 6672601C>T, Tyr89=
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs1891311 -1188T>C, 4056T>C, 43423080A>G, 92618616A>G
A > G
5' Flanking
No VIP available CA VA
rs1935349 28329G>A, 43398807C>T, 539+22547G>A, 92594343C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2020933 -221+876T>A, 28561755A>T, 3298749A>T, 6200T>A
A > T
Intronic
No VIP available CA VA
rs2032582 186947T>A, 186947T>G, 25193461A>C, 25193461A>T, 2677A, 2677G, 2677T, 2677T>A, 2677T>G, 3095G>T/A, 87160618A>C, 87160618A>T, 893 Ala, 893 Ser, 893 Thr, ABCB1*7, ABCB1: 2677G>T/A, ABCB1: 2677T/A>G, ABCB1: A893S, ABCB1: G2677T/A, ABCB1: c.2677G>T/A, ABCB1:2677G>A/T, ABCB1:2677G>T/A, ABCB1:A893T, Ala893Ser/Thr, MDR1, MDR1 G2677T/A, Ser893Ala, Ser893Thr, mRNA 3095G>T/A, p.Ala893Ser/Thr
A > C
A > T
Missense
Ser893Ala
Ser893Thr
No VIP available No Clinical Annotations available VA
rs20455 2155T>C, 39265078A>G, 39325078A>G, KIF6:Trp719Arg, Trp719Arg
A > G
Missense
Trp719Arg
No VIP available No Clinical Annotations available VA
rs2228314 1784G>C, 21667311G>C, 42276742G>C, Gly595Ala
G > C
Missense
Gly595Ala
No VIP available CA VA
rs2231142 13600044G>T, 32689C>A, 421C>A, 89052323G>T, ABCG2: Q141K, ABCG2:421C>A, ABCG2:Q141K, ABCG2:c.421C>A, Gln141Lys, rs2231142
G > T
Missense
Gln141Lys
No VIP available CA VA
rs2276307 113803887A>G, 17366303A>G, 33299A>G, 696+72A>G
A > G
Intronic
rs2306283 14089862A>G, 21329738A>G, 388A>G, 50611A>G, Asn130Asp, SLCO1B1*1B
A > G
Missense
Asn130Asp
No VIP available No Clinical Annotations available VA
rs2740574 -392G>A, 37414939C>T, 4713G>A, 5'-flanking region -392A>G, 99382096C>T, CYP3A4*1B, CYP3A4-V, CYP3A4:-392A>G
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs35599367 20493C>T, 37399159G>A, 522-191C>T, 99366316G>A, CYP3A4*22
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs3758987 -381T>C, 113775275T>C, 17337691T>C, 4687T>C
T > C
5' Flanking
rs3846662 1564-106A>G, 1722+45A>G, 23092A>G, 25245443A>G, 74651084A>G
A > G
Intronic
No VIP available CA VA
rs3917643 10547A>G, 213-147A>G, 64973785T>C, 95001867T>C
T > C
Intronic
VIP No Clinical Annotations available No Variant Annotations available
rs4149015 -910G>A, 14043446G>A, 21283322G>A, 4195G>A, SLCO1B1:11187G>A, SLCO1B1:G-11187A
G > A
5' Flanking
rs4149056 14091673T>C, 21331549T>C, 521T>C, 52422T>C, SLCO1B1*5, Val174Ala
T > C
Missense
Val174Ala
No VIP available No Clinical Annotations available VA
rs4149081 14138145G>A, 1865+248G>A, 21378021G>A, 98894G>A, OATP1B1: intronic A/G
G > A
Intronic
No VIP available CA VA
rs4253728 209-1003G>A, 26000636G>A, 46610067G>A, 68569G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs4363657 14128846T>C, 1498-1331T>C, 21368722T>C, 89595T>C
T > C
Intronic
No VIP available CA VA
rs4673 214T>C, 273853A>G, 88713236A>G, 9222T>C, His72Tyr polymorphism in the p22phox subunit, Tyr72His
A > G
Missense
Tyr72His
No VIP available No Clinical Annotations available VA
rs4693075 18900C>G, 779-1022C>G, 84192168G>C, 8739889G>C
G > C
Intronic
No VIP available CA VA
rs4823613 208+3819A>G, 25988876A>G, 46598307A>G, 56809A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs539748 -147+2217T>C, -238+2217T>C, 113821349T>C, 253681T>C, 7799T>C
C > T
Intronic
No VIP available CA VA
rs5882 10630291G>A, 1264G>A, 25258G>A, 57016092G>A, CETP:I405V, CETP:Ile405Val, CETP:rs5882 A>G
G > A
Missense
Val422Ile
No VIP available No Clinical Annotations available VA
rs60282872 -34delG, 17343539delC, 17740165delC, 5161delG, NC_000017.10:g.17740165delC, NM_001005291.2:c.-34delG, NM_004176.4:c.-34delG, del abolished ApaI restriction site
C > -
5' UTR
No VIP available No Clinical Annotations available VA
rs6312 -344G>A, 145G>A, 28450824C>T, 47470824C>T, 5346G>A, Asp49Asn
C > T
Missense
Asp49Asn
No VIP available No Clinical Annotations available VA
rs6318 113965735G>C, 152185G>C, 398067G>C, 68G>C, Cys23Ser, HTR2C:23Ser, HTR2C:Cys23Ser
C > G
Missense
Cys23Ser
No VIP available No Clinical Annotations available VA
rs659734 28415283G>A, 362-25509C>T, 40887C>T, 47435283G>A, 614-25509C>T
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs662 21439A>G, 32970289T>C, 575A>G, 94937446T>C, Gln192Arg
T > C
Missense
Gln192Arg
No VIP available CA VA
rs662799 -620C>T, -644C>T, 116663707G>A, 20226123G>A, 4430C>T
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs676643 -628C>T, 10201428G>A, 23521340G>A
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs705379 -108C>T, 32986738G>A, 4990C>T, 94953895G>A
G > A
5' Flanking
No VIP available CA VA
rs708272 10610487G>A, 118+279G>A, 5454G>A, 56996288G>A, A allele = B2 = not cut by TaqI, CETP:Taq1B, G allele = B1 = cut by TaqI
G > A
Intronic
No VIP available CA VA
rs717620 -24C>T, 101542578C>T, 5116C>T, 52347042C>T, ABCC2: 5'UTR, ABCC2:(-24)C>T, mRNA 118C>T
C > T
5' UTR
No VIP available CA VA
rs7412 17680297C>T, 45412079C>T, 526C>T, 8041C>T, APOE epsilon 2, ApoE2, Arg176Cys
C > T
Missense
Arg176Cys
rs776746 12083G>A, 219-237G>A, 321-1G>A, 37303382C>T, 581-237G>A, 689-1G>A, 99270539C>T, CYP3A5*1, CYP3A5*3, CYP3A5*3C, CYP3A5:6986A>G, g.6986A>G, intron 3 splicing defect, rs776746 A>G
C > T
Acceptor
No VIP available No Clinical Annotations available VA
rs8014194 76720678T>A, 83-24208A>T, 95720678T>A
T > A
Intronic
No VIP available CA VA
rs9806699 16530949G>A, 45740392G>A
G > A
Not Available
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

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

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

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.
  1. Statin Pathway, Pharmacodynamics
    Genes involved in mediating statin effects on hepatic cholesterol metabolism and consequent effects on plasma lipoprotein transport.

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)
F2 (source: Drug Bank)
HMGCR (source: Drug Bank)
ICAM1 (source: Drug Bank)
IFNG (source: Drug Bank)
IL6 (source: Drug Bank)
IL8 (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

Drug Description
simvastatin Increased risk of rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of rhabdomyolysis (source: Drug Bank)
simvastatin Amprenavir can possibly increase the statin toxicity (source: Drug Bank)
simvastatin Amprenavir can possibly increase the statin toxicity (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Bosentan could decrease the statin effect (source: Drug Bank)
simvastatin Bosentan could decrease the statin effect (source: Drug Bank)
simvastatin Decreases the effect of the statin (source: Drug Bank)
simvastatin Decreases the effect of the statin (source: Drug Bank)
simvastatin The macrolide possibly increases the statin toxicity (source: Drug Bank)
simvastatin The macrolide, clarithromycin, may increase the toxicity of the statin, simvastatin. (source: Drug Bank)
simvastatin Increased risk of rhabdomyolysis with this combination (source: Drug Bank)
simvastatin Increased risk of rhabdomyolysis with this combination (source: Drug Bank)
simvastatin Possible myopathy and rhabdomyolysis (source: Drug Bank)
simvastatin Possible myopathy and rhabdomyolysis (source: Drug Bank)
simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
simvastatin Increases the effect and toicity of simvastatin (source: Drug Bank)
simvastatin Increases the effect and toicity of simvastatin (source: Drug Bank)
simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
simvastatin The macrolide possibly increases the statin toxicity (source: Drug Bank)
simvastatin The macrolide, erythromycin, may increase the toxicity of the statin, simvastatin. (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Amprenavir can possibly increase the statin toxicity (source: Drug Bank)
simvastatin Amprenavir can possibly increase the statin toxicity (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Imatinib increases the effect and toxicity of statin (source: Drug Bank)
simvastatin Imatinib increases the effect and toxicity of statin (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Increased risk of myopathy/rhabdomyolysis (source: Drug Bank)
simvastatin Nefazodone increases the effect and toxicity of the statin drug (source: Drug Bank)
simvastatin Nefazodone increases the effect and toxicity of the statin drug (source: Drug Bank)
simvastatin Nelfinavir increases the effect and toxicity of the statin (source: Drug Bank)
simvastatin Nelfinavir increases the effect and toxicity of the statin (source: Drug Bank)
simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
simvastatin The NNRT inhibitor increases the effect and toxicity of the statin (source: Drug Bank)
simvastatin This combination presents an increased risk of toxicity (source: Drug Bank)
simvastatin Ranolazine increases the statin level (source: Drug Bank)
simvastatin The rifamycin decreases the effect of the statin drug (source: Drug Bank)
simvastatin The rifamycin decreases the effect of the statin drug (source: Drug Bank)
simvastatin The rifamycin decreases the effect of the statin drug (source: Drug Bank)
simvastatin The rifamycin decreases the effect of the statin drug (source: Drug Bank)
simvastatin Telithromycin may possibly increase statin toxicity (source: Drug Bank)
simvastatin Telithromycin may reduce clearance of Simvastatin. Concomitant therapy is contraindicated. (source: Drug Bank)
simvastatin Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Simvastatin. Concomitant therapy is contraindicated. (source: Drug Bank)
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)
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

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Clinically actionable genotypes among 10,000 patients with preemptive pharmacogenomic testing. Clinical pharmacology and therapeutics. 2013. Van Driest Sara L, et al. PubMed
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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
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Applied Pharmacogenomics in Cardiovascular Medicine. Annual review of medicine. 2013. Weeke Peter, et al. PubMed
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Characterization of Statin Dose-response within Electronic Medical Records. Clinical pharmacology and therapeutics. 2013. Wei Wei-Qi, et al. PubMed
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Statin induced changes in gene expression in EBV-transformed and native B-cells. Human molecular genetics. 2013. Bolotin Eugene, et al. PubMed
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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
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A statin-dependent QTL for GATM expression is associated with statin-induced myopathy. Nature. 2013. Mangravite Lara M, et al. PubMed
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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
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International transporter consortium commentary on clinically important transporter polymorphisms. Clinical pharmacology and therapeutics. 2013. Giacomini K M, et al. PubMed
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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
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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
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Amlodipine - Not a Significant Contributor to Clopidogrel Non-Response?. Heart (British Cardiac Society). 2013. Kreutz Rolf P, et al. PubMed
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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
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CYP3A4*22: promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy. Pharmacogenomics. 2013. Elens Laure, et al. PubMed
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Correction: Enteric Microbiome Metabolites Correlate with Response to Simvastatin Treatment. PloS one. 2013. Kaddurah-Daouk Rima, et al. PubMed
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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
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Pharmacogenomics in clinical practice and drug development. Nature biotechnology. 2012. Harper Andrew R, et al. PubMed
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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
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PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenetics and genomics. 2012. Lamba Jatinder, et al. PubMed
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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
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The Clinical Pharmacogenomics Implementation Consortium: CPIC Guideline for SLCO1B1 and Simvastatin-Induced Myopathy. Clinical pharmacology and therapeutics. 2012. Wilke R A, et al. PubMed
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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
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Metabolomics reveals amino acids contribute to variation in response to simvastatin treatment. PloS one. 2012. Trupp Miles, et al. PubMed
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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
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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
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Disease-drug-drug interaction involving tocilizumab and simvastatin in patients with rheumatoid arthritis. Clinical pharmacology and therapeutics. 2011. Schmitt C, et al. PubMed
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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
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Pharmacogenomics: the genetics of variable drug responses. Circulation. 2011. Roden Dan M, et al. PubMed
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Transporter-Mediated Drug Uptake and Efflux: Important Determinants of Adverse Drug Reactions. Clinical pharmacology and therapeutics. 2011. Zolk O, et al. PubMed
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Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
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PharmGKB: very important pharmacogene--HMGCR. Pharmacogenetics and genomics. 2011. Medina Marisa Wong, et al. PubMed
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Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. PubMed
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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
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Enteric microbiome metabolites correlate with response to simvastatin treatment. PloS one. 2011. Kaddurah-Daouk Rima, et al. PubMed
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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
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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
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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
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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
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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
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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
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Genetic and clinical predictors of warfarin dose requirements in African Americans. Clinical pharmacology and therapeutics. 2010. Cavallari L H, et al. PubMed
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Pharmacogenomics of membrane transporters: past, present and future. Pharmacogenomics. 2010. Yee Sook Wah, et al. PubMed
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Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. The pharmacogenomics journal. 2010. Wang D, et al. PubMed
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PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenetics and genomics. 2010. Oshiro Connie, et al. PubMed
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Common sequence variants in pharmacodynamic and pharmacokinetic pathway-related genes conferring LDL cholesterol response to statins. Pharmacogenomics. 2010. Chien Kuo-Liong, et al. PubMed
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Transporter pharmacogenetics and statin toxicity. Clinical pharmacology and therapeutics. 2010. Niemi M. PubMed
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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
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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
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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
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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
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Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Hauswald Stefanie, et al. PubMed
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Statin regulation of CYP3A4 and CYP3A5 expression. Pharmacogenomics. 2009. Willrich Maria Alice Vieira, et al. PubMed
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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
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Impact of OATP transporters on pharmacokinetics. British journal of pharmacology. 2009. Kalliokoski A, et al. PubMed
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Medicinal Chemistry of Drugs used in Diabetic Cardiomyopathy. Current medicinal chemistry. 2009. Adeghate E, et al. PubMed
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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
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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
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Genetic determinants of response to clopidogrel and cardiovascular events. The New England journal of medicine. 2009. Simon Tabassome, et al. PubMed
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The role of HMGCR alternative splicing in statin efficacy. Trends in cardiovascular medicine. 2009. Medina Marisa Wong, et al. PubMed
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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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Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities. Antioxidants & redox signaling. 2009. Kuo Macus Tien. PubMed
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Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008. Luna-Tortós Carlos, 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
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Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
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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
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Machine learning methods and docking for predicting human pregnane X receptor activation. Chemical research in toxicology. 2008. Khandelwal Akash, et al. PubMed
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Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhou S-F. PubMed
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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
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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
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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
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Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008. Uhr Manfred, et al. PubMed
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Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacological research : the official journal of the Italian Pharmacological Society. 2008. Nikisch Georg, et al. PubMed
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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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Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2007. Marguerite Véronique, et al. PubMed
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Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. Molecular pharmaceutics. 2007. Collnot Eva-Maria, 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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Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer research. 2006. Leggas Markos, 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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Impact of P-glycoprotein on clopidogrel absorption. Clinical pharmacology and therapeutics. 2006. Taubert Dirk, 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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Single nucleotide polymorphisms in human P-glycoprotein: its impact on drug delivery and disposition. Expert opinion on drug delivery. 2006. Dey Surajit. 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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Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenetics and genomics. 2005. Kameyama Yoshio, et al. PubMed
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
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA : the journal of the American Medical Association. 2004. Chasman Daniel I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Influence of lipid lowering fibrates on P-glycoprotein activity in vitro. Biochemical pharmacology. 2004. Ehrhardt Manuela, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharmaceutical research. 2004. Hochman Jerome H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Lipid-lowering response to statins is affected by CYP3A5 polymorphism. Pharmacogenetics. 2004. Kivistö Kari T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clinical pharmacology and therapeutics. 2004. Marzolini Catia, 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 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
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Genetic polymorphisms of the human MDR1 drug transporter. Annual review of pharmacology and toxicology. 2003. Schwab Matthias, 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-atherosclerotic effect of simvastatin depends on the presence of apolipoprotein E. Atherosclerosis. 2002. Wang Yi Xin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. The Journal of biological chemistry. 2001. Tirona R G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn-Schmiedeberg's archives of pharmacology. 2001. Pauli-Magnus 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
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. The Journal of clinical investigation. 1999. Greiner 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
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annual review of pharmacology and toxicology. 1999. Ambudkar S V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Competitive, non-competitive and cooperative interactions between substrates of P-glycoprotein as measured by its ATPase activity. Biochimica et biophysica acta. 1997. Litman T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
P-glycoprotein structure and evolutionary homologies. Cytotechnology. 1993. Croop J M. 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, Open Eye Scientific Software.