Drug/Small Molecule:
maraviroc

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

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


last updated 10/25/2013

FDA Label for maraviroc and CCR5

This label is on the FDA Biomarker List
Genetic testing required

Summary

The drug labeling for maraviroc is not related to genetic testing of the patient, rather testing of the HIV-1 strain that has infected the patient. The FDA-approved label states that HIV tropism testing be carried out before treatment with Maraviroc. This drug is indicated only for CCR5-tropic HIV-1 infection, and due to its mechanism of action, is not effective against CXCR4-tropic and dual-tropic HIV-1.

Annotation

Maraviroc (Selzentry) is a CCR5 antagonist, and works by preventing HIV-1 from entering cells via the CCR5 cell surface receptor. The drug labeling information demonstrates why a sensitive HIV tropism assay should be used to diagnose CCR5-tropic HIV-1, in order to avoid treating individuals with CXCR4- or Dual/ Mixed- tropic virus (discussed in section 14.3).

Maraviroc is principally metabolized by CYP3A enzymes. Drug labeling information also includes Maraviroc dosage recommendations if CYP3A inhibitors or CYP3A inducers are taken concomitantly.

Excerpt from the maraviroc drug label:

SELZENTRY, in combination with other antiretroviral agents, is indicated for adult
patients infected with only CCR5-tropic HIV-1.


The following points should be considered when initiating therapy with SELZENTRY:

  • Adult patients infected with only CCR5-tropic HIV-1 should use SELZENTRY.
  • Tropism testing must be conducted with a highly sensitive tropism assay that has demonstrated the ability to identify patients appropriate for use of SELZENTRY. Outgrowth of pre-existing low-level CXCR4-or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on SELZENTRY

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Maraviroc drug label.

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

Genes and/or phenotypes found in this label

  • CCR5
    • Indications & usage section, Information for patients section, Description section, Clinical studies section, Mechanism of action section, Pharmacokinetics section, Warnings and precautions section, Microbiology section, efficacy
    • source: FDA Label
  • CYP3A4
    • Dosage & administration section, Contraindications section, Drug interactions section, Overdosage section, Pharmacokinetics section, Use in specific populations section, Warnings and precautions section, dosage
    • source: FDA Label
  • CYP3A5
    • Dosage & administration section, Contraindications section, Drug interactions section, Overdosage section, Pharmacokinetics section, Use in specific populations section, Warnings and precautions section, dosage
    • source: FDA Label

European Medicines Agency (EMA) Label for maraviroc and CCR5

Genetic testing required

Summary

The drug labeling for maraviroc is not related to genetic testing of the patient, rather testing of the HIV-1 strain that has infected the patient. The EMA European Public Assessment Report (EPAR) for Maraviroc (CELSENTRI) contains information regarding its indication only in patients with CCR5-tropic HIV-1 and not CXCR4- or dual/mixed tropic virus, due to its mechanism of action as a CCR5 antagonist.

Annotation

The EPAR details that a test on newly drawn blood should be carried out prior to treatment to confirm only CCR5-tropic HIV-1 virus is detectable and treatment should be started soon after the test. Under safety data, the EPAR states that no significant adverse consequences in humans that lack CCR5 expression due to genetic deletion have been reported.

Excerpts from the Maraviroc (CELSENTRI) EPAR:

Maraviroc selectively binds to the human chemokine receptor CCR5, preventing CCR5-tropic HIV-1 from entering cells.


Maraviroc has no antiviral activity in vitro against viruses which can use CXCR4 as their entry co-receptor (dual-tropic or CXCR4-tropic viruses).


Before taking CELSENTRI it has to be confirmed that only CCR5-tropic HIV-1 is detectable (i.e. CXCR4 or dual/mixed tropic virus not detected) using an adequately validated and sensitive detection method on a newly drawn blood sample. The Monogram Trofile assay was used in the clinical studies of CELSENTRI (see sections 4.4 and 5.1). Other phenotypic and genotypic assays are currently being evaluated. The viral tropism cannot be safely predicted by treatment history and assessment of stored samples.

This information is highlighted in the following sections:
Therapeutic indications, posology and method of administration, tropism, pharmacodynamic properties, preclinical safety data, package leaflet - information for the user.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Maraviroc (CELSENTRI) EMA drug label.

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


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?
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • maraviroc
Trade Names
  • Celsentri
  • Selzentry
Brand Mixture Names

PharmGKB Accession Id:
PA164768835

Description

Maraviroc (brand-named Selzentry, or Celsentri outside the U.S.) is a chemokine receptor antagonist drug developed by the drug company Pfizer that is designed to act against HIV by interfering with the interaction between HIV and CCR5. It was originally labelled as UK-427857 during development but was assigned the Maraviroc name as it entered trials. It was approved for use by the FDA in August, 2007.

Source: Drug Bank

Indication

For treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Maraviroc is an entry inhibitor and works by blocking HIV from entering human cells. Specifically maraviroc is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR5 and HIV-1 gp120. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the membrane of CD4 cells (T-cells), preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.

Source: Drug Bank

Pharmacology

Maraviroc is a chemokine receptor antagonist drug developed by the drug company Pfizer that is designed to act against HIV by interfering with the interaction between HIV and CCR5.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

In vitro studies indicate that CYP3A is the major enzyme responsible for maraviroc metabolism.

Source: Drug Bank

Protein Binding

Approximately 76% bound to human plasma proteins, with moderate affinity for albumin and alpha-1 acid glycoprotein.

Source: Drug Bank

Absorption

The absolute oral bioavailability of a 100 mg dose is 23% and is predicted to be 33% at 300 mg. Coadministration of a 300mg tablet with a high fat breakfast reduced maraviroc Cmax and AUC by 33% in healthy volunteers.

Source: Drug Bank

Half-Life

14-18 hours

Source: Drug Bank

Volume of Distribution

  • 194 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C29H41F2N5O

Source: Drug Bank

Isomeric SMILES

CC1=NN=C(N1[C@@H]2C[C@H]3CC[C@@H](C2)N3CC[C@@H](C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C

Source: Drug Bank

[H][C@]12CC[C@]([H])(CC(C1)N1C(C)=NN=C1C(C)C)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)C1=CC=CC=C1

Source: Drug Bank

Canonical SMILES

CC(C)C1=NN=C(C)N1C1C[C@@H]2CC[C@H]

Source: Drug Bank

Average Molecular Weight

513.6655

Source: Drug Bank

Monoisotopic Molecular Weight

513.327917369

Source: Drug Bank

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 ?

EvidenceGene
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CCR5
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A4
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A5

Drug Targets

Gene Description
CCR5 (source: Drug Bank)

Drug Interactions

Drug Description
maraviroc Telithromycin may reduce clearance of Maraviroc. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Maraviroc if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank)
maraviroc Topiramate, a CYP3A4 inducer, may decrease the serum concentration of Maraviroc by increasing Maraviroc metabolism and clearance. A dose adjustment of Maraviroc may be required. Monitor for changes in Maraviroc therapeutic and adverse effects if Topiramate is initiated, discontinued or dose changed. (source: Drug Bank)
maraviroc Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of maraviroc by decreasing its metabolism. A dose reduction in maraviroc is warranted. Monitor for changes in the therapeutic and adverse effects of maraviroc if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank)
No related diseases are available

Publications related to maraviroc: 3

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, 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 Dual Role of Pharmacogenetics in HIV Treatment: Mutations and Polymorphisms Regulating Antiretroviral Drug Resistance and Disposition. Pharmacological reviews. 2012. Michaud Veronique, 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
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0069-0807-60
DrugBank:
DB04835
PubChem Compound:
3002977
PubChem Substance:
12015618
46508040
IUPHAR Ligand:
803
806
ChemSpider:
2273675
Therapeutic Targets Database:
DNC001487
FDA Drug Label at DailyMed:
a94a9a2b-337b-4c13-8622-fc392194dc21

Clinical Trials

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

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