Maraviroc is indicated, in combination with other antiretroviral medications, for the treatment of only CCR5-tropic HIV-1 infection.[2][3]
Side effectsedit
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.[6] Official labeling of Selzentry has black box warning for hepatotoxicity.[2] The MOTIVATE trials showed no clinically relevant differences in safety between the maraviroc and placebo groups.[7]
Mechanism of actionedit
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.[8] 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.[9]
Historyedit
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,[10] and the drug received full FDA approval on 6 August 2007 for use in treatment experienced patients.[11]
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.[7][12][13] Maraviroc was approved for medical use in the European Union in September 2007.[3]
^"FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
^ abcdefghijk"Selzentry- maraviroc tablet, film coated Selzentry- maraviroc solution". DailyMed. 18 July 2018. Retrieved 31 July 2020.
^Abel S, Russell D, Whitlock LA, Ridgway CE, Nedderman AN, Walker DK (April 2008). "Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects". British Journal of Clinical Pharmacology. 65 (Suppl 1): 60–7. doi:10.1111/j.1365-2125.2008.03137.x. PMC2311408. PMID 18333867.
^Abel S, Back DJ, Vourvahis M (2009). "Maraviroc: pharmacokinetics and drug interactions". Antiviral Therapy. 14 (5): 607–18. doi:10.1177/135965350901400514. PMID 19704163. S2CID 29064286.
^"Maraviroc (HIV treatment) Dosage, Side Effects". AIDSinfo.
^ abStephenson J (April 2007). "Researchers buoyed by novel HIV drugs: will expand drug arsenal against resistant virus". JAMA. 297 (14): 1535–6. doi:10.1001/jama.297.14.1535. PMID 17426263.
^Levy JA (January 2009). "HIV pathogenesis: 25 years of progress and persistent challenges". AIDS. 23 (2): 147–60. doi:10.1097/QAD.0b013e3283217f9f. PMID 19098484. S2CID 10571856.
^Biswas P, Tambussi G, Lazzarin A (May 2007). "Access denied? The status of co-receptor inhibition to counter HIV entry". Expert Opinion on Pharmacotherapy. 8 (7): 923–33. doi:10.1517/14656566.8.7.923. PMID 17472538. S2CID 32675897.
^Krauskopf, Lewis (6 August 2007). "Pfizer wins U.S. approval for new HIV drug". Reuters. Retrieved 6 August 2007.
^Emmelkamp JM, Rockstroh JK (October 2007). "CCR5 antagonists: comparison of efficacy, side effects, pharmacokinetics and interactions--review of the literature". European Journal of Medical Research. 12 (9): 409–17. PMID 17933722.
^"Maraviroc reduces viral load in naive patients at 48 weeks". AIDS Patient Care and STDs. 21 (9): 703–4. September 2007. PMID 17941136.
^World Health Organization (2005). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 53". WHO Drug Information. 19 (1): 84–5. hdl:10665/73323. License: CC BY-NC-SA 3.0 IGO.
^Reshef R, Luger SM, Hexner EO, Loren AW, Frey NV, Nasta SD, et al. (July 2012). "Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease". N. Engl. J. Med. 367 (2): 135–45. doi:10.1056/NEJMoa1201248. PMC3568501. PMID 22784116.
^"HIV Drug Reduces Graft-versus-Host Disease in Bone Marrow Transplant Patients, Penn Study Shows". Penn Medicine (Press release).
Further readingedit
Dean L (2015). "Maraviroc Therapy and CCR5 Genotype". In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.). Medical Genetics Summaries. National Center for Biotechnology Information (NCBI). PMID 28520358. Bookshelf ID: NBK279895.
External linksedit
"Maraviroc". Drug Information Portal. U.S. National Library of Medicine.
maraviroc, sold, under, brand, names, selzentry, celsentri, antiretroviral, medication, used, treat, infection, taken, mouth, ccr5, receptor, antagonist, class, clinical, datapronunciation, selzentry, trade, namesselzentry, celsentriother, namesuk, 427857, dif. Maraviroc sold under the brand names Selzentry US and Celsentri EU is an antiretroviral medication used to treat HIV infection 2 3 It is taken by mouth 2 3 It is in the CCR5 receptor antagonist class 2 3 MaravirocClinical dataPronunciation m e ˈ r ae v ɪ r ɒ k me RAV i rok Selzentry s ɛ l ˈ z ɛ n t r i Trade namesSelzentry CelsentriOther namesUK 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 cyclohexanecarboxamideAHFS Drugs comMonographMedlinePlusa607076License dataEU EMA by INN US FDA MaravirocPregnancycategoryAU B1Routes ofadministrationBy mouthATC codeJ05AX09 WHO Legal statusLegal statusUK POM Prescription only US WARNING 1 Rx only 2 EU Rx only 3 Pharmacokinetic dataBioavailability23 4 Protein binding 76 2 MetabolismLiver CYP predominantly CYP3A 2 MetabolitesSecondary amine formed by N dealkylation major Elimination half life14 18 hours 2 mean 16 hours 5 ExcretionFeces 76 urine 20 2 IdentifiersIUPAC 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 cyclohexanecarboxamideCAS Number376348 65 1 YPubChem CID3002977IUPHAR BPS806DrugBankDB04835 YChemSpider20078004 NUNIIMD6P741W8AChEBICHEBI 63608 NChEMBLChEMBL1201187 NNIAID ChemDB104834CompTox Dashboard EPA DTXSID8048949ECHA InfoCard100 124 927Chemical and physical dataFormulaC 29H 41F 2N 5OMolar mass513 678 g mol 13D model JSmol Interactive imageSMILES Cc5nnc n5 C H 1C C H 4CC C H C1 N4CC C H NC O C2CCC F F CC2 c3ccccc3 C C CInChI InChI 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 NKey GSNHKUDZZFZSJB QYOOZWMWSA N N N Y what is this verify It was approved for medical use in the United States in August 2007 2 and in the European Union in September 2007 3 Contents 1 Medical uses 2 Side effects 3 Mechanism of action 4 History 5 Names 6 Research 7 References 8 Further reading 9 External linksMedical uses editMaraviroc is indicated in combination with other antiretroviral medications for the treatment of only CCR5 tropic HIV 1 infection 2 3 Side effects editMaraviroc 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 6 Official labeling of Selzentry has black box warning for hepatotoxicity 2 The MOTIVATE trials showed no clinically relevant differences in safety between the maraviroc and placebo groups 7 Mechanism of action editMaraviroc 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 8 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 9 History editMaraviroc 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 10 and the drug received full FDA approval on 6 August 2007 for use in treatment experienced patients 11 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 mL in the once daily group 106 cells mL in the twice daily group and 56 cells mL in the placebo group 7 12 13 Maraviroc was approved for medical use in the European Union in September 2007 3 Names editMaraviroc is the International nonproprietary name INN 14 Research editMaraviroc appears to reduce graft versus host disease in people treated with allogeneic bone marrow transplantation for leukemia in a Phase I II study 15 16 References edit FDA sourced list of all drugs with black box warnings Use Download Full Results and View Query links nctr crs fda gov FDA Retrieved 22 October 2023 a b c d e f g h i j k Selzentry maraviroc tablet film coated Selzentry maraviroc solution DailyMed 18 July 2018 Retrieved 31 July 2020 a b c d e f g Celsentri EPAR European Medicines Agency EMA 17 September 2018 Retrieved 31 July 2020 Abel S Russell D Whitlock LA Ridgway CE Nedderman AN Walker DK April 2008 Assessment of the absorption metabolism and absolute bioavailability of maraviroc in healthy male subjects British Journal of Clinical Pharmacology 65 Suppl 1 60 7 doi 10 1111 j 1365 2125 2008 03137 x PMC 2311408 PMID 18333867 Abel S Back DJ Vourvahis M 2009 Maraviroc pharmacokinetics and drug interactions Antiviral Therapy 14 5 607 18 doi 10 1177 135965350901400514 PMID 19704163 S2CID 29064286 Maraviroc HIV treatment Dosage Side Effects AIDSinfo a b Stephenson J April 2007 Researchers buoyed by novel HIV drugs will expand drug arsenal against resistant virus JAMA 297 14 1535 6 doi 10 1001 jama 297 14 1535 PMID 17426263 Levy JA January 2009 HIV pathogenesis 25 years of progress and persistent challenges AIDS 23 2 147 60 doi 10 1097 QAD 0b013e3283217f9f PMID 19098484 S2CID 10571856 Biswas P Tambussi G Lazzarin A May 2007 Access denied The status of co receptor inhibition to counter HIV entry Expert Opinion on Pharmacotherapy 8 7 923 33 doi 10 1517 14656566 8 7 923 PMID 17472538 S2CID 32675897 Gay News From 365Gay com Krauskopf Lewis 6 August 2007 Pfizer wins U S approval for new HIV drug Reuters Retrieved 6 August 2007 Emmelkamp JM Rockstroh JK October 2007 CCR5 antagonists comparison of efficacy side effects pharmacokinetics and interactions review of the literature European Journal of Medical Research 12 9 409 17 PMID 17933722 Maraviroc reduces viral load in naive patients at 48 weeks AIDS Patient Care and STDs 21 9 703 4 September 2007 PMID 17941136 World Health Organization 2005 International nonproprietary names for pharmaceutical substances INN recommended INN list 53 WHO Drug Information 19 1 84 5 hdl 10665 73323 License CC BY NC SA 3 0 IGO Reshef R Luger SM Hexner EO Loren AW Frey NV Nasta SD et al July 2012 Blockade of lymphocyte chemotaxis in visceral graft versus host disease N Engl J Med 367 2 135 45 doi 10 1056 NEJMoa1201248 PMC 3568501 PMID 22784116 HIV Drug Reduces Graft versus Host Disease in Bone Marrow Transplant Patients Penn Study Shows Penn Medicine Press release Further reading editDean L 2015 Maraviroc Therapy and CCR5 Genotype In Pratt VM McLeod HL Rubinstein WS et al eds Medical Genetics Summaries National Center for Biotechnology Information NCBI PMID 28520358 Bookshelf ID NBK279895 External links edit Maraviroc Drug Information Portal U S National Library of Medicine Maraviroc at the U S National Library of Medicine Medical Subject Headings MeSH Portals nbsp Medicine nbsp Viruses Retrieved from https en wikipedia org w index php title Maraviroc amp oldid 1220384518, wikipedia, wiki, book, books, library,
