maraviroc

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 477499940

| image = Maraviroc.svg

| image_class = skin-invert-image

| width = 275

| alt = Structural formula of maraviroc

| image2 = Maraviroc molecule ball.png

| width2 = 250

| alt2 = Ball-and-stick model of the maraviroc molecule

| pronounce = {{IPAc-en|m|ə|ˈ|r|æ|v|ᵻ|r|ɒ|k}} {{respell|mə|RAV|i-rok}} Selzentry: {{IPAc-en|s|ɛ|l|ˈ|z|ɛ|n|t|r|i}}

| tradename = Selzentry, Celsentri

| Drugs.com = {{drugs.com|monograph|maraviroc}}

| DailyMedID = Maraviroc

| MedlinePlus = a607076

| pregnancy_AU = B1

| pregnancy_category =

| routes_of_administration = By mouth

| ATC_prefix = J05

| ATC_suffix = AX09

| legal_AU = S4

| legal_AU_comment = {{cite web | title=Maraviroc Waymade (Waymade Australia Pty Limited) | website=Therapeutic Goods Administration (TGA) | date=14 January 2025 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/maraviroc-waymade-waymade-australia-pty-limited | access-date=20 January 2025}}

| legal_CA =

| legal_UK = POM

| legal_US = Rx-only

| legal_US_comment =

| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Celsentri EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/celsentri | access-date=31 July 2020}}

| legal_status =

| bioavailability = 23%{{cite journal |vauthors=Abel S, Russell D, Whitlock LA, Ridgway CE, Nedderman AN, Walker DK | title = Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects | journal = British Journal of Clinical Pharmacology | volume = 65 | issue = Suppl 1 | pages = 60–7 |date=April 2008 | pmid = 18333867 | pmc = 2311408 | doi = 10.1111/j.1365-2125.2008.03137.x}}

| protein_bound = ~76%{{cite web | title=Selzentry- maraviroc tablet, film coated Selzentry- maraviroc solution | website=DailyMed | date=18 July 2018 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=46f30ac5-c96b-429e-976d-8c5ee1c0761b | access-date=31 July 2020}}

| metabolism = Liver (CYP, predominantly CYP3A)

| metabolites = Secondary amine formed by N-dealkylation (major)

| elimination_half-life = 14–18 hours (mean 16 hours){{cite journal |vauthors=Abel S, Back DJ, Vourvahis M | title = Maraviroc: pharmacokinetics and drug interactions | journal = Antiviral Therapy | volume = 14 | issue = 5 | pages = 607–18 | year = 2009 | doi = 10.1177/135965350901400514 | pmid = 19704163| s2cid = 29064286 | doi-access = free }}

| excretion = Feces (76%), urine (20%)

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 376348-65-1

| PubChem = 3002977

| IUPHAR_ligand = 806

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB04835

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 20078004

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = MD6P741W8A

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 63608

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1201187

| NIAID_ChemDB = 104834

| IUPAC_name = 4,4-Difluoro-N-{(1S)-3-[3-(3-isopropyl- 5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1-phenylpropyl}cyclohexanecarboxamide

| C=29 | H=41 | F=2 | N=5 | O=1

| SMILES = Cc5nnc(n5[C@@H]1C[C@H]4CC[C@@H](C1)N4CC[C@H](NC(=O)C2CCC(F)(F)CC2)c3ccccc3)C(C)C

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C29H41F2N5O/c1-19(2)27-34-33-20(3)36(27)25-17-23-9-10-24(18-25)35(23)16-13-26(21-7-5-4-6-8-21)32-28(37)22-11-14-29(30,31)15-12-22/h4-8,19,22-26H,9-18H2,1-3H3,(H,32,37)/t23-,24+,25-,26-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = GSNHKUDZZFZSJB-QYOOZWMWSA-N

| synonyms = UK-427857, 4,4-Difluoro-N-[(1S)-3-{(1R,3s,5S)-3-[3-methyl-5-(propan-2-yl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]octan-8-yl}-1-phenylpropyl]
cyclohexanecarboxamide

}}

Maraviroc, sold under the brand names Selzentry (US) and Celsentri (EU), is an antiretroviral medication used to treat HIV infection. It is taken by mouth. It is in the CCR5 receptor antagonist class.

It was approved for medical use in the United States in August 2007, and in the European Union in September 2007.

Medical uses

Maraviroc is indicated, in combination with other antiretroviral medications, for the treatment of only CCR5-tropic HIV-1 infection.

Side effects

Maraviroc can cause serious, life-threatening side effects. These include liver problems, skin reactions, and allergic reactions. An allergic reaction may happen before liver problems occur.{{cite web|url=https://aidsinfo.nih.gov/drugs/408/maraviroc--hiv-treatment/0/patient|title=Maraviroc (HIV treatment) Dosage, Side Effects|website=AIDSinfo|access-date=6 June 2019|archive-date=20 February 2020|archive-url=https://web.archive.org/web/20200220023821/https://aidsinfo.nih.gov/drugs/408/maraviroc--hiv-treatment/0/patient|url-status=dead}} Official labeling of Selzentry has black box warning for hepatotoxicity. The MOTIVATE trials showed no clinically relevant differences in safety between the maraviroc and placebo groups.

Mechanism of action

Maraviroc is an entry inhibitor. Specifically, maraviroc is a negative allosteric modulator of the CCR5 receptor, which is found on the surface of certain human cells. The chemokine receptor CCR5 is an essential co-receptor for most HIV strains and necessary for the entry process of the virus into the host cell. The drug binds to CCR5, thereby blocking the HIV protein gp120 from associating with the receptor. HIV is then unable to enter human macrophages and T cells.{{cite journal |author=Levy JA |title=HIV pathogenesis: 25 years of progress and persistent challenges |journal=AIDS |volume=23 |issue=2 |pages=147–60 |date=January 2009 |pmid=19098484 |doi=10.1097/QAD.0b013e3283217f9f|s2cid=10571856 |doi-access=free }} Because HIV can also use other coreceptors, such as CXCR4, an HIV tropism test such as a trofile assay must be performed to determine if the drug will be effective.{{cite journal |vauthors=Biswas P, Tambussi G, Lazzarin A |title=Access denied? The status of co-receptor inhibition to counter HIV entry |journal=Expert Opinion on Pharmacotherapy |volume=8 |issue=7 |pages=923–33 |date=May 2007 |pmid=17472538 |doi=10.1517/14656566.8.7.923|s2cid=32675897 }}

History

Maraviroc, originally designated UK-427857, was developed by the drug company Pfizer in its UK labs located in Sandwich. On 24 April 2007 the U.S. Food and Drug Administration advisory panel reviewing maraviroc's New Drug Application unanimously recommended approval for the new drug,[http://365gay.com/Newscon07/04/042407hiv.htm Gay News From 365Gay.com] and the drug received full FDA approval on 6 August 2007 for use in treatment experienced patients.{{cite news |url=https://www.reuters.com/article/ousiv/idUSN0642522320070806 |title=Pfizer wins U.S. approval for new HIV drug | work=Reuters |access-date=6 August 2007 | first=Lewis | last=Krauskopf | date=6 August 2007}}

Two randomized, placebo-controlled clinical trials, compared 209 people receiving optimized therapy plus a placebo to 426 people receiving optimized therapy plus 150 mg maraviroc once daily and 414 patients receiving optimized therapy plus 150 mg maraviroc twice daily. At 48 weeks, 55% of participants receiving maraviroc once daily and 60% of participants receiving the drug twice daily achieved a viral load of less than 400 copies/mL compared with 26% of those taking placebo; about 44% of the once-daily and 45% of the twice-daily maraviroc group had a viral load of less than 50 copies/mL compared with about 23% of those who received placebo. In addition, those who received the entry inhibitor had a mean increase in CD4⁺ cells of 110 cells/μL in the once-daily group, 106 cells/μL in the twice-daily group, and 56 cells/μL in the placebo group.{{cite journal |author=Stephenson J |title=Researchers buoyed by novel HIV drugs: will expand drug arsenal against resistant virus |journal=JAMA |volume=297 |issue=14 |pages=1535–6 |date=April 2007 |pmid=17426263 |doi=10.1001/jama.297.14.1535}}{{cite journal |vauthors=Emmelkamp JM, Rockstroh JK |title=CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature |journal=European Journal of Medical Research |volume=12 |issue=9 |pages=409–17 |date=October 2007 |pmid=17933722}}{{cite journal |title=Maraviroc reduces viral load in naive patients at 48 weeks |journal=AIDS Patient Care and STDs |volume=21 |issue=9 |pages=703–4 |date=September 2007 |pmid=17941136}} Maraviroc was approved for medical use in the European Union in September 2007.

Names

Maraviroc is the International nonproprietary name (INN).{{cite journal | vauthors=((World Health Organization)) | year=2005 | title=International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 53 | journal=WHO Drug Information | volume=19 | issue=1 | pages=84–5 | hdl=10665/73323 | hdl-access=free | id=License: CC BY-NC-SA 3.0 IGO }}

Research

Maraviroc appears to reduce graft-versus-host disease in people treated with allogeneic bone marrow transplantation for leukemia, in a Phase I/II study.{{cite journal |vauthors=Reshef R, Luger SM, Hexner EO, Loren AW, Frey NV, Nasta SD, Goldstein SC, Stadtmauer EA, Smith J, Bailey S, Mick R, Heitjan DF, Emerson SG, Hoxie JA, Vonderheide RH, Porter DL | display-authors=6 |title=Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease |journal=N. Engl. J. Med. |volume=367 |issue=2 |pages=135–45 |date=July 2012 |pmid=22784116 |pmc=3568501 |doi=10.1056/NEJMoa1201248 }}{{cite press release |url=https://www.pennmedicine.org/news/news-releases/2012/july/hiv-drug-reduces-graftversusho|title=HIV Drug Reduces Graft-versus-Host Disease in Bone Marrow Transplant Patients, Penn Study Shows|website=Penn Medicine}}