Drug/Small Molecule:
mycophenolic acid

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PharmGKB annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency, Japan (PMDA). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.

Sources:

  • FDA Information is gathered from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" and from FDA-approved labels brought to our attention. Please note that drugs may be removed from or added to the FDA's Table without our knowledge. We periodically check the Table for changes and update PharmGKB accordingly. Drugs listed on the Table to our knowledge are tagged with the Biomarker icon. A drug label that has been removed from the Table will not have the Biomarker icon but will continue to have an annotation on PharmGKB stating the label has been removed from the FDA's Table. We acquire label PDF files from DailyMed.
  • EMA European Public Assessment Reports (EPARs) that contain PGx information were identified from [Article:24433361] and also by searching for drugs for which we have PGx-containing FDA drug labels.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA, PMDA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for mycophenolic acid and HPRT1

Actionable PGx

Summary

Myfortic is an IMPDH Inhibitor that should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.

Annotation

The FDA Pharmacogenomic Biomarkers in Drug Labels table lists HGPRT as a biomarker for mycophenolic acid, with information contained in the Precautions section.

Excerpts from the mycophenolic acid (Myfortic) drug label:

Myfortic is an inosine monophosphate dehydrogenase inhibitor (IMPDH Inhibitor). Myfortic should be avoided in patients with rare hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes because it may cause an exacerbation of disease symptoms characterized by the overproduction and accumulation of uric acid leading to symptoms associated with gout such as acute arthritis, tophi, nephrolithiasis or urolithiasis and renal disease including renal failure.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the mycophenolic acid (Myfortic) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Leukopenia
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • HPRT1
    • Warnings and precautions section, toxicity
    • source: FDA Label

Pharmaceuticals and Medical Devices Agency, Japan (PMDA) Label for mycophenolic acid and HPRT1

Actionable PGx

Summary

The PMDA package insert for mycophenolic acid notes that it should be avoided in patients with hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndromes, due to the risk for exacerbation of hyperuricemia.

Annotation

Please note that the information contained within this drug label annotation is sourced from Shimazawa and Ikeda (2013), whose paper provided a translation of the pharmacogenetic information contained in the PMDA package insert.

Excerpt from the package insert for mycophenolic acid:

Mycophenolic Acid is an inosine monophosphate dehydrogenase (IMPDH) inhibitor. Therefore, it should be avoided in patients with hereditary deficiencies of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome, because hyperuricemia could be exacerbated by mycophenolic acid.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the mycophenolic acid package insert (in Japanese).

*Disclaimer: The contents of this page have not been endorsed by the PMDA and are the sole responsibility of PharmGKB.

Genes and/or phenotypes found in this label

  • HPRT1
    • Precautions section, toxicity
    • source: Pharmaceuticals and Medical Devices Agency, Japan (PMDA) Label

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

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?

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 mycophenolic acid variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs10187694 234545583G>A, 415G>A, 491842G>A, 52194G>A, 855+18375G>A, Glu139Lys
G > A
Missense
Glu139Lys
No VIP available No Clinical Annotations available VA
rs1042597 234526871C>G, 234526871C>T, 33482C>G, 33482C>T, 473130C>G, 473130C>T, 518C>G, 518C>T, Ala173Gly, Ala173Val, UGT1A8*2
C > G
C > T
Missense
Ala173Val
Ala173Gly
No VIP available CA VA
rs11706052 49004110A>G, 49064110A>G, 7766T>C, 819+10T>C, IMPDH2:IVS7+10T>C
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs17863762 234527183G>A, 33794G>A, 473442G>A, 830G>A, Cys277Tyr, UGT1A8: UGT1A8*3
G > A
Missense
Cys277Tyr
No VIP available No Clinical Annotations available VA
rs17863778 234590974C>A, 391C>A, 537233C>A, 855+44951C>A, 855+63766C>A, 855+9539C>A, 97585C>A, Arg131=
C > A
Intronic
Arg131Arg
No VIP available No Clinical Annotations available VA
rs17868320 234578428C>T, 524687C>T, 85039C>T, 855+32405C>T, 855+51220C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs17868323 234590970T>G, 387T>G, 537229T>G, 855+44947T>G, 855+63762T>G, 855+9535T>G, 97581T>G, Asn129Lys, UGT1A7:N129K, rs17868323
T > G
Intronic
Asn129Lys
No VIP available CA VA
rs2273697 101563815G>A, 1249G>A, 26353G>A, 52368279G>A, ABCC2: c.1249G>A, ABCC2:1249G>A, ABCC2:V417I, ABCC2:c.1249G>A, Val417Ile, p.V417I
G > A
Missense
Val417Ile
No VIP available No Clinical Annotations available VA
rs2278293 128040752C>T, 14285G>A, 250-159G>A, 309+134G>A, 324+119G>A, 471+119G>A, 480+119G>A, 549+119G>A, 579+119G>A, 66073595C>T, IMPDH1:IVS7+125G4A
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2278294 128040699C>T, 14338G>A, 250-106G>A, 310-106G>A, 325-106G>A, 472-106G>A, 481-106G>A, 550-106G>A, 580-106G>A, 66073542C>T, IMPDH1:IVS8-106G4A
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2306283 14089862A>G, 21329738A>G, 388A>G, 50611A>G, Asn130Asp, SLCO1B1*1B
A > G
Missense
Asn130Asp
No VIP available No Clinical Annotations available VA
rs2741045 -441C>T, 234580140C>T, 526399C>T, 855+34117C>T, 855+52932C>T, 86751C>T
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs2741046 -332T>C, 234580249T>C, 526508T>C, 855+34226T>C, 855+53041T>C, 86860T>C
T > C
5' Flanking
No VIP available No Clinical Annotations available VA
rs3740066 101604207C>T, 3972C>T, 52408671C>T, 66745C>T, ABCC2:3972C>T, I1324I, Ile1324=
C > T
Synonymous
Ile1324Ile
No VIP available No Clinical Annotations available VA
rs3832043 -127delT, 10, 234580454delT, 526713delT, 855+34431delT, 855+53246delT, 87065delT, 9/, T, UGT1A9*22, UGT1A9:
T > -
5' Flanking
No VIP available No Clinical Annotations available VA
rs4149056 14091673T>C, 21331549T>C, 521T>C, 52422T>C, SLCO1B1*5, Val174Ala
T > C
Missense
Val174Ala
No VIP available No Clinical Annotations available VA
rs6714486 -276T>A, 234580305T>A, 526564T>A, 855+34282T>A, 855+53097T>A, 86916T>A
T > A
5' Flanking
No VIP available No Clinical Annotations available 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 No Clinical Annotations available VA
rs73823859 -138G>A, 10172768G>A, 69962101G>A
G > A
5' Flanking
No VIP available No Clinical Annotations available VA
rs7439366 10175005T>C, 69964338T>C, 802T>C, Tyr268His, UGT2B7*2, UGT2B7:802C>T, UGT2B7:H268Y, UGT2B7Y
T > C
Missense
Tyr268His
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Mycophenoic acid
Trade Names
  • Melbex
  • Myfortic
Brand Mixture Names

PharmGKB Accession Id:
PA164748728

Description

Mycophenolic acid is an an immunosuppresant drug and potent anti-proliferative, and can be used in place of the older anti-proliferative azathioprine. It is usually used as part of triple therapy including a calcineurin inhibitor (ciclosporin or tacrolimus) and prednisolone. It is also useful in research for the selection of animal cells that express the E. coli gene coding for XGPRT (xanthine guanine phosphoribosyltransferase).

Source: Drug Bank

Indication

For the prophylaxis of organ rejection in patients receiving allogeneic renal transplants, administered in combination with cyclosporine and corticosteroids.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Mycophenolic acid is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Because T- and B-lymphocytes are critically dependent for their proliferation on de novo synthesis of purines, whereas other cell types can utilize salvage pathways, mycophenolic acid has potent cytostatic effects on lymphocytes. Mycophenolic acid inhibits proliferative responses of T- and B-lymphocytes to both mitogenic and allospecific stimulation. Addition of guanosine or deoxyguanosine reverses the cytostatic effects of mycophenolic acid on lymphocytes. Mycophenolic acid also suppresses antibody formation by B-lymphocytes. Mycophenolic acid prevents the glycosylation of lymphocyte and monocyte glycoproteins that are involved in intercellular adhesion to endothelial cells and may inhibit recruitment of leukocytes into sites of inflammation and graft rejection.

Source: Drug Bank

Pharmacology

Mycophenolic acid is an antibiotic substance derived from Penicillium stoloniferum. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Mycophenolic acid is metabolized mainly by glucuronyl transferase to glucuronidated metabolites, predominantly the phenolic glucuronide, mycophenolic acid glucuronide (MPAG). MPAG does not manifest pharmacological activity. The acyl glucuronide minor metabolite has pharmacological activity similar to mycophenolic acid. The AUC ratio of Mycophenolic acid:MPAG:acyl glucuronide is approximately 1:24:0.28 at steady state.

Source: Drug Bank

Protein Binding

>98%

Source: Drug Bank

Absorption

Bioavailability following oral administration of Myfortic delayed-release tablet ranges from 70-95%

Source: Drug Bank

Half-Life

The mean elimination half-life for mycophenolic acid ranges from 8-16 hours, while that of the MPAG metabolite ranges from 13-17 hours.

Source: Drug Bank

Toxicity

Oral (LD50): Acute: 352 mg/kg Rat, 1000 mg/kg Mouse, and >6000 mg/kg Rabbit. Possible signs and symptoms of acute overdose could include the following: hematological abnormalities such as leukopenia and neutropenia, and gastrointestinal symptoms such as abdominal pain, diarrhea, nausea and vomiting, and dyspepsia.

Source: Drug Bank

Clearance

Source: Drug Bank

Volume of Distribution

  • 54 ┬▒ 25 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C17H20O6

Source: Drug Bank

Isomeric SMILES

CC1=C2COC(=O)C2=C(C(=C1OC)C/C=C(\C)/CCC(=O)O)O

Source: Drug Bank

COC1=C(C)C2=C(C(=O)OC2)C(O)=C1C\C=C(/C)CCC(O)=O

Source: Drug Bank

Canonical SMILES

COC1=C(C\C=C(/C)CCC(O)=O)C(O)=C2C(=O)OCC2=C1C

Source: Drug Bank

Average Molecular Weight

320.3371

Source: Drug Bank

Monoisotopic Molecular Weight

320.125988372

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics
    Schematic representation of mycophenolic acid metabolism.

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
IMPDH1 (source: Drug Bank)
IMPDH2 (source: Drug Bank)
No related drugs are available.

Curated Information ?

Publications related to mycophenolic acid: 20

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Population pharmacogenetic pharmacokinetic modeling for flip-flop phenomenon of enteric-coated mycophenolate sodium in kidney transplant recipients. European journal of clinical pharmacology. 2014. Han Nayoung, 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 cytochrome P450, family 2, subfamily C, polypeptide 8. Pharmacogenetics and genomics. 2013. Aquilante Christina L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Population pharmacokinetics of unbound mycophenolic acid in adult allogeneic haematopoietic cell transplantation: effect of pharmacogenetic factors. British journal of clinical pharmacology. 2013. Frymoyer Adam, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Inosine monophosphate dehydrogenase polymorphisms and renal allograft outcome. Transplantation. 2012. Shah Sapna, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Mycophenolic acid-related anemia and leucopenia in renal transplant recipients are related to genetic polymorphisms in CYP2C8. Transplantation. 2012. Bouamar Rachida, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Lymphocyte counts in kidney allograft recipients are associated with IMPDH2 3757T>C gene polymorphism. Transplantation proceedings. 2011. Pazik J, 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
Mycophenolic acid response biomarkers: A cell line model system-based genome-wide screen. International immunopharmacology. 2011. Wu Tse-Yu, 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
Seasonal variation in blood drug concentrations and a potential relationship to vitamin D. Drug metabolism and disposition: the biological fate of chemicals. 2011. Lindh Jonatan D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Genetic determinants of mycophenolate-related anemia and leukopenia after transplantation. Transplantation. 2011. Jacobson Pamala A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
SLCO1B1 genetic polymorphism influences mycophenolic acid tolerance in renal transplant recipients. Pharmacogenomics. 2010. Michelon Hugues, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Polymorphisms in type I and II inosine monophosphate dehydrogenase genes and association with clinical outcome in patients on mycophenolate mofetil. Pharmacogenetics and genomics. 2010. Gensburger Olivier, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Correlation of IMPDH1 gene polymorphisms with subclinical acute rejection and mycophenolic acid exposure parameters on day 28 after renal transplantation. Basic & clinical pharmacology & toxicology. 2010. Kagaya Hideaki, 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 No Variant Annotation available No VIP available No VIP available
Pharmacogenetic influences on mycophenolate therapy. Pharmacogenomics. 2010. Barraclough Katherine A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
An inosine 5'-monophosphate dehydrogenase 2 single-nucleotide polymorphism impairs the effect of mycophenolic acid. The pharmacogenomics journal. 2010. Winnicki W, 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 organic anion-transporting polypeptides and their common genetic variants in mycophenolic acid pharmacokinetics. Clinical pharmacology and therapeutics. 2010. Picard 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
Increased mycophenolic acid exposure in stable kidney transplant recipients on tacrolimus as compared with those on sirolimus: implications for pharmacokinetics. Clinical pharmacology and therapeutics. 2009. Braun F, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Interpatient variability in IMPDH activity in MMF-treated renal transplant patients is correlated with IMPDH type II 3757T > C polymorphism. Pharmacogenetics and genomics. 2009. Sombogaard Ferdi, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Influence of uridine diphosphate (UDP)-glucuronosyltransferases and ABCC2 genetic polymorphisms on the pharmacokinetics of mycophenolic acid and its metabolites in Chinese renal transplant recipients. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhang W-X, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Association of four DNA polymorphisms with acute rejection after kidney transplantation. Transplant international : official journal of the European Society for Organ Transplantation. 2008. Griny├│ Josep, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0078-0386-66
DrugBank:
DB01024
PDB:
MOA
ChEBI:
168396
PubChem Compound:
446541
PubChem Substance:
46504559
602720
Drugs Product Database (DPD):
2264560
BindingDB:
19264
ChemSpider:
393865
HET:
MOA
Therapeutic Targets Database:
DAP000784
FDA Drug Label at DailyMed:
eed26501-890d-4ff6-88e7-6dbea4726e53

Clinical Trials

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

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.