Generic placeholder image

Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

Review Article

A Combination of Novel HIV-1 Protease Inhibitor and Cytochrome P450 (CYP) Enzyme Inhibitor to Explore the Future Prospective of Antiviral Agents: Evotaz

Author(s): Abha Sharma, Poonam Sharma, Isha Kapila and Vikrant Abbot*

Volume 21, Issue 3, 2023

Published on: 26 June, 2023

Page: [149 - 159] Pages: 11

DOI: 10.2174/1570162X21666230522123631

Price: $65

Abstract

Viruses belong to the class of micro-organisms that are well known for causing infections in the human body. Antiviral medications are given out to prevent the spread of disease-causing viruses. When the viruses are actively reproducing, these agents have their greatest impact. It is particularly challenging to develop virus-specific medications since viruses share the majority of the metabolic functions of the host cell. In the continuous search for better antiviral agents, the United States Food and Drug Administration (USFDA) approved a new drug named Evotaz on January 29, 2015 for the treatment of human immunodeficiency virus (HIV). Evotaz is a combined once-daily fixed drug, containing Atazanavir, an HIV protease inhibitor, and cobicistat, an inhibitor of the human liver cytochrome P450 (CYP) enzyme. The medication is created such that it can kill viruses by concurrently inhibiting protease and CYP enzymes. The medicine is still being studied for a number of criteria, but its usefulness in children under the age of 12 is currently unknown. The preclinical and clinical characteristics of Evotaz, as well as its safety and efficacy profiles and a comparison of the novel drug with antiviral medications presently available in the market, are the main topics of this review paper.

Graphical Abstract

[1]
Harnden MR. Approaches to Antiviral Agents. Berlin: Springer 2016.
[2]
Chen Y, Chen HY, Lee CY. Inhibiting viral replication and prolonging survival of hosts by attenuating stress responses to viral infection. J Invertebr Pathol 2022; 190: 107753.
[http://dx.doi.org/10.1016/j.jip.2022.107753] [PMID: 35358596]
[3]
Granich R, Williams B. HIV treatment: Time to lean forward. Lancet 2016; 387(10013): 27.
[http://dx.doi.org/10.1016/S0140-6736(15)01293-3] [PMID: 26766341]
[4]
Shen Y, Zhang C, Valimaki M, Qian H, Mohammadi L, Chi Y, et al. Why do men who have sex with men practice condomless sex? A systematic review and meta-synthesis. BMC Infect Dis 2022; 22(1): 850.
[5]
Hiv C, Long H. AIDS. Med Care 2012; 916: 874-7720.
[6]
Razonable RR. Antiviral drugs for viruses other than human immunodeficiency virus. Mayo Clin Proc 2011; 86(10): 1009-26.
[7]
Narang B, Grewal G, Roy S, Bariwal J, Gupta M, Rawal R. A novel integrase targeting agent to explore the future prospective of HIV eradication: Dolutegravir. Curr HIV Res 2014; 12(5): 325-38.
[http://dx.doi.org/10.2174/1570162X12666140807150753] [PMID: 25106411]
[8]
Gallo RC, Montagnier L. The discovery of HIV as the cause of AIDS. N Engl J Med 2003; 349(24): 2283-5.
[http://dx.doi.org/10.1056/NEJMp038194] [PMID: 14668451]
[9]
Ferreira CMS, Sunada NMO, Casseb J. T-lymphocyte activation markers in patients with HIV-1-associated neurocognitive disorder. J Neurovirol 2022; 28(3): 404-9.
[http://dx.doi.org/10.1007/s13365-022-01075-2] [PMID: 35527311]
[10]
Jurkat T. Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors. Retrovirology 2013; 10: 101.
[11]
Broder S, Fauci AS. Progress in drug therapies for HIV infection. Public Health Rep 1988; 103(3): 224-9.
[PMID: 3131811]
[12]
Daluge SM, Martin MT, Sickles BR, Livingston DA. An efficient, scalable synthesis of the HIV reverse transcriptase inhibitor Ziagen (1592U89). Nucleosides Nucleotides Nucleic Acids 2000; 19(1-2): 297-327.
[http://dx.doi.org/10.1080/15257770008033011] [PMID: 10772717]
[13]
Perry CM, Noble S. Didanosine. Drugs 1999; 58(6): 1099-135.
[http://dx.doi.org/10.2165/00003495-199958060-00009] [PMID: 10651392]
[14]
Patel M, Ko SS, McHugh RJ Jr, et al. Synthesis and evaluation of analogs of Efavirenz (SUSTIVATM) as HIV-1 reverse transcriptase inhibitors. Bioorg Med Chem Lett 1999; 9(19): 2805-10.
[http://dx.doi.org/10.1016/S0960-894X(99)00486-2] [PMID: 10522695]
[15]
Boswell RF, Gupton BF, Lo YS. Method for making nevirapine. US6680383B1, 2004.
[16]
Intelence™(etravirine) tablets. US prescribing information [online]. 2022. Available From: http://www.intelence-info.com/intelence/assets/pdf/
[17]
Swainston Harrison T, Scott LJ. Atazanavir. Drugs 2005; 65(16): 2309-36.
[http://dx.doi.org/10.2165/00003495-200565160-00010] [PMID: 16266202]
[18]
U.S. Food and Drug Administration (FDA) approves PREZISTA once-daily as part of combination therapy for treatment-naive adults with HIV-1. 2008. Available From: https://www.natap.org/2008/HIV/102208_01.htm
[19]
Pham P. Drug profile: fosamprenavir (Lexiva). The Hopkins HIV Report 2003; 15(6): 10-1.
[20]
Williams IG. Enfuvirtide (Fuzeon): The first fusion inhibitor. Int J Clin Pract 2003; 57(10): 890-7.
[PMID: 14712892]
[21]
Kuritzkes D, Kar S, Kirkpatrick P. Maraviroc. Nat Rev Drug Discov 2008; 7(1): 15-6.
[http://dx.doi.org/10.1038/nrd2490] [PMID: 19008887]
[22]
Food and Drug Administration. Approval of Tybost (cobicistat) 150 mg tablets. HIV/AIDS Update [Internet]. 2014. Available From: https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/203094Orig2s000ltr.pdf
[23]
Lyseng-Williamson KA, Deeks ED. Cobicistat: A guide to its use as a pharmacokinetic enhancer of atazanavir and darunavir in HIV-1 infection. Drugs Ther Perspect 2014; 30(9): 309-15.
[http://dx.doi.org/10.1007/s40267-014-0143-3]
[24]
Podzamczer D, Ferrer E, Consiglio E, et al. A randomized clinical trial comparing nelfinavir or nevirapine associated to zidovudine/lamivudine in HIV-infected naive patients (the Combine Study). Antivir Ther 2002; 7(2): 81-90.
[http://dx.doi.org/10.1177/135965350200700202] [PMID: 12212928]
[25]
John M, McKinnon EJ, James IR, Nolan DA, Herrmann SE, Moore CB, et al. Randomized, controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in hiv-infected patients. JAIDS 2003; 33(2): 29-33.
[26]
Corbett AH, Lim ML, Kashuba ADM. Kaletra (lopinavir/ritonavir). Ann Pharmacother 2002; 36(7-8): 1193-203.
[http://dx.doi.org/10.1345/aph.1A363] [PMID: 12086554]
[27]
Seaton ORA, Fox R, Bodasing N, Peters SE, Gourlay Y. Effect of co-formulated zidovudine, lamivudine and abacavir (Trizivir) on antiretroviral-naive patients presenting with advanced HIV-1 infection. AIDS 2003; 17(3): 445-7.
[http://dx.doi.org/10.1097/00002030-200302140-00021] [PMID: 12556701]
[28]
Shey M, Kongnyuy EJ, Shang J, Wiysonge CS. A combination drug of abacavir-lamivudine-zidovudine (Trizivir) for treating HIV infection and AIDS. Cochrane Database Syst Rev 2009; (3): CD005481.
[PMID: 19588374]
[29]
Camp R. Epzicom Brand Abacavir-Lamivudine QD. 2004. Available From: https://www.treatmentactiongroup.org/publication/epzicom-brand-abacavir-lamivudine-qd/
[30]
James JS. FDA approves two combination pills, Epzicom and Truvada; comment on commercial race to once-a-day nucleosides. AIDS Treat News 2004; (403): 6.
[PMID: 15386855]
[31]
De Clercq E. From adefovir to Atripla™via tenofovir, Viread™ and Truvada™. Future Med 2006; 1(6): 709-15.
[32]
García-Lerma JG. Intermittent prophylaxis with oral truvada protects macaques from rectal SHIV infection. Sci Transl Med 2010; 2(14): 14ra4.
[33]
Deeks ED, Perry CM. Efavirenz/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen (Atripla®): A review of its use in the management of HIV infection. Drugs 2010; 70(17): 2315-38.
[http://dx.doi.org/10.2165/11203800-000000000-00000] [PMID: 21080746]
[34]
Food, Administration D. FDA approval of complera. 2011. Available From: mtricitabine/rilpivirine/tenofovir DF fixed dose combination
[35]
Bernardini C, Maggiolo F. Triple-combination rilpivirine, emtricitabine, and tenofovir (Complera™/Eviplera™) in the treatment of HIV infection. Patient Prefer Adherence 2013; 7: 531-42.
[PMID: 23814462]
[36]
Breeze S. Novel HIV-1 treatment Stribild™ gains regulatory approval. Expert Rev Clin Pharmacol 2012; 5(6): 613.
[PMID: 23234321]
[37]
Olin JL, Spooner LM, Klibanov OM. Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single tablet for HIV-1 infection treatment. Ann Pharmacother 2012; 46(12): 1671-7.
[http://dx.doi.org/10.1345/aph.1R468] [PMID: 23136357]
[40]
Clinical Review Report. Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (EVG/COBI/FTC/TAF) (Genvoya) Fixed-Dose Combination, Oral Tablet). Canada: Canadian Agency for Drugs and Technologies in Health 2015.
[41]
Alafenamide T. Genvoya: A new 4-drug combination for HIV. JAMA 2016; 316(2): 215-6.
[42]
Drug Database: Emtricitabine/Rilpiviprine/ Tenofovir Alfenamide. 2017. Available from: https://clinicalinfo.hiv.gov/en/drugs/emtricitabine-rilpivirine-tenofovir-alafenamide/patient
[43]
Kalapila AG, Marrazzo J. Antiretroviral therapy for prevention of Human Immunodeficiency Virus Infection. Med Clin North Am 2016; 100(4): 927-50.
[http://dx.doi.org/10.1016/j.mcna.2016.03.013] [PMID: 27235622]
[44]
Canadian AIDS Treatment Information Exchange. Descovy Approved in Canada-Key Information. 2016. Available from: https://www.catie.ca/sites/default/files/2021-09/descovy%20EN%202021%2008%2018.pdf
[45]
Antunes F. Atazanavir sulfate + cobicistat for the treatment of HIV infection. Expert Rev Anti Infect Ther 2017; 15(6): 569-76.
[http://dx.doi.org/10.1080/14787210.2017.1323634] [PMID: 28443391]
[46]
Orkin C, DeJesus E, Ramgopal M, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide coformulated with rilpivirine and emtricitabine in virally suppressed adults with HIV-1 infection: A randomised, double-blind, multicentre, phase 3b, non-inferiority study. Lancet HIV 2017; 4(5): e195-204.
[http://dx.doi.org/10.1016/S2352-3018(17)30031-0] [PMID: 28259777]
[47]
Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380–1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet 2017; 390(10107): 2073-82.
[http://dx.doi.org/10.1016/S0140-6736(17)32340-1] [PMID: 28867499]
[48]
Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): A double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet 2017; 390(10107): 2063-72.
[http://dx.doi.org/10.1016/S0140-6736(17)32299-7] [PMID: 28867497]
[49]
Deeks ED. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide: A review in HIV-1 infection. Drugs 2018; 78(10): 1013-24.
[http://dx.doi.org/10.1007/s40265-018-0934-2] [PMID: 29915897]
[50]
Johnson M, Kumar P, Molina J-M, Rizzardini G, Cahn P, Bickel M, et al. Brief Report: Switching to DOR/3TC/TDF maintains HIV-1 virologic suppression through week 144 in the DRIVE-SHIFT trial. J Acquir Immune Defic Syndr 2021; 87(2): 801-5.
[51]
SYMFI LO- efavirenz, lamivudine and tenofovir disoproxil fumarate tablet, film coated. 2018. Available From: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86aad85d-5460-4c38-9761-a225e6bce190
[52]
Joly V, Burdet C, Landman R, et al. Dolutegravir and lamivudine maintenance therapy in HIV-1 virologically suppressed patients: Results of the ANRS 167 trial (LAMIDOL). J Antimicrob Chemother 2019; 74(3): 739-45.
[http://dx.doi.org/10.1093/jac/dky467] [PMID: 30476165]
[53]
Markham A. Cabotegravir plus rilpivirine: First approval. Drugs 2020; 80(9): 915-22.
[http://dx.doi.org/10.1007/s40265-020-01326-8] [PMID: 32495274]
[54]
2015 PIPELINE REPORT. 2015. Available from: https://i-base.info/2015-pipeline-report-launched-at-ias/
[55]
Hossain MA. New drugs approval. Bangl Pharm J 2015; 18(1): 83-4.
[http://dx.doi.org/10.3329/bpj.v18i1.23524]
[56]
Artacho MÁ, Barreiro P, Fernández-Montero JV. Long-term treatment of patients with HIV-1: The role of atazanavir. HIV AIDS 2010; 2: 157-66.
[PMID: 22096394]
[57]
Babu VVR, Sharma PK, Singhvi I. A new gradient liquid chromatographic method for simultaneous estimation of tenofovir disoproxil fumarate, cobicistat, emtricitabine and elvitegravir in bulk drug and tablet dosage form. Asian J Chem 2014; 26(18): 6233-7.
[http://dx.doi.org/10.14233/ajchem.2014.17196]
[58]
Fan X, Song YL, Long YQ. An efficient and practical synthesis of the hiv protease inhibitor atazanavir via a highly diastereoselective reduction approach. Org Process Res Dev 2008; 12(1): 69-75.
[http://dx.doi.org/10.1021/op7001563]
[59]
Xu L, Liu H, Murray BP, et al. Cobicistat (GS-9350): A potent and selective inhibitor of human CYP3A as a novel pharmacoenhancer. ACS Med Chem Lett 2010; 1(5): 209-13.
[http://dx.doi.org/10.1021/ml1000257] [PMID: 24900196]
[60]
Chaves OA, Sacramento CQ, Ferreira AC, et al. Atazanavir is a competitive inhibitor of SARS-CoV-2 Mpro, impairing variants replication in vitro and in vivo. Pharmaceuticals 2021; 15(1): 21.
[http://dx.doi.org/10.3390/ph15010021] [PMID: 35056078]
[61]
Cabrera FA, Romacho JU, Peralta AJ, Vaquero DG, Garcia MA, Rosa AM, et al. 5PSQ-048 Darunavir/cobicistat pharmacological interactions: Clinical relevance and action mechanism. In: Eur J Hosp Pharm 2018; 25(Suppl 1): A186.
[62]
López-Cortés LF. Pharmacology, pharmacokinetic features and interactions of atazanavir. Enferm Infecc Microbiol Clin 2008; 26 (Suppl. 17): 2-8.
[PMID: 20116610]
[63]
Sherman EM, Worley MV, Unger NR, Gauthier TP, Schafer JJ. Cobicistat: Review of a pharmacokinetic enhancer for HIV infection. Clin Ther 2015; 37(9): 1876-93.
[http://dx.doi.org/10.1016/j.clinthera.2015.07.022] [PMID: 26319088]
[64]
Busti AJ, Hall RG II, Margolis DM. Atazanavir for the treatment of human immunodeficiency virus infection. Pharmacotherapy 2004; 24(12): 1732-47.
[http://dx.doi.org/10.1592/phco.24.17.1732.52347] [PMID: 15585441]
[65]
Shiomi M, Matsuki S, Ikeda A, et al. Effects of a protein‐rich drink or a standard meal on the pharmacokinetics of elvitegravir, cobicistat, emtricitabine and tenofovir in healthy Japanese male subjects: A randomized, three-way crossover study. J Clin Pharmacol 2014; 54(6): 640-8.
[http://dx.doi.org/10.1002/jcph.283] [PMID: 24615728]
[66]
Le Tiec C, Barrail A, Goujard C, Taburet AM. Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir. Clin Pharmacokinet 2005; 44(10): 1035-50.
[http://dx.doi.org/10.2165/00003088-200544100-00003] [PMID: 16176117]
[67]
Marin RC, Behl T, Negrut N, Bungau S. Management of antiretroviral therapy with boosted protease inhibitors—darunavir/ritonavir or darunavir/cobicistat. Biomedicines 2021; 9(3): 313.
[http://dx.doi.org/10.3390/biomedicines9030313] [PMID: 33803812]
[68]
Gammal RS, Court MH, Haidar CE, et al. Clinical pharmacogenetics implementation consortium (CPIC) guideline for UGT1A1 and atazanavir prescribing. Clin Pharmacol Ther 2016; 99(4): 363-9.
[http://dx.doi.org/10.1002/cpt.269] [PMID: 26417955]
[69]
Cattaneo D, Cossu MV, Rizzardini G. Pharmacokinetic drug evaluation of ritonavir (versus cobicistat) as adjunctive therapy in the treatment of HIV. Expert Opin Drug Metab Toxicol 2019; 15(11): 927-35.
[http://dx.doi.org/10.1080/17425255.2019.1685495] [PMID: 31668105]
[70]
Mikus G, Foerster KI, Schaumaeker M, Lehmann ML, Burhenne J, Haefeli WE. Application of a microdosed cocktail of 3 oral factor Xa inhibitors to study drug–drug interactions with different perpetrator drugs. Br J Clin Pharmacol 2020; 86(8): 1632-41.
[http://dx.doi.org/10.1111/bcp.14277] [PMID: 32159869]
[71]
Croom KF, Dhillon S, Keam SJ. Atazanavir: A review of its use in the management of HIV-1 infection. Drugs 2009; 69(8): 1107-40.
[http://dx.doi.org/10.2165/00003495-200969080-00009] [PMID: 19496633]
[72]
Perry CM. Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen (Stribild®): A review of its use in the management of HIV-1 infection in adults. Drugs 2014; 74(1): 75-97.
[http://dx.doi.org/10.1007/s40265-013-0158-4] [PMID: 24338165]
[73]
Klibanov OM, Phan D, Ferguson K. Atazanavir and cobicistat (Evotaz). Nurse Pract 2015; 40(12): 35.
[PMID: 26545091]
[74]
Branning G. Once-fatal conditions have become chronic: Early trends in the FDA's 2015 lrovals. Am Health Drug Benefits 2015; 8(Spec Feature): 167-70.
[75]
Rakemann T. Comparative study of the different approaches for approval of new HIV drugs to guidelines of the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) including possible implications on future drug development. Masters Thesis. Germany: Rbeimische Friedrich Wilhelms Universitat 2015. 2015.
[76]
Huhn GD, Wilkin A, Mussini C, et al. Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen in antiretroviral treatment (ART)-naïve and -experienced, virologically-suppressed adults living with HIV-1. HIV Res Clin Pract 2020; 21(6): 151-67.
[http://dx.doi.org/10.1080/25787489.2020.1844520] [PMID: 33528318]
[77]
NIH. A Phase 3, randomized, double-blind study to evaluate the safety and efficacy of gs-9350-boosted atazanavirversus ritonavir-boosted atazanavir each administered with emtricitabine/tenofovir disoproxil fumarate in HIV-1 infected, antiretroviral treatment-naive adults. 2022. Available From: https://adisinsight.springer.com/trials/700055741
[78]
Bailey H, Zash R, Rasi V, Thorne C. HIV treatment in pregnancy. Lancet HIV 2018; 5(8): e457-67.
[http://dx.doi.org/10.1016/S2352-3018(18)30059-6] [PMID: 29958853]
[79]
Talukdar D, Jain V, Balaramnavar V, Srivastava SP, Sivanandy P, Gupta MM. Potential drugs for COVID-19 treatment management with their contraindications and drug-drug interaction. Med Pharmacol 2021; 1: 1-34.
[http://dx.doi.org/10.20944/preprints202105.0690.v1]
[80]
Vanangamudi M, Priya GR, Engels M. Current and Promising multiclass drug regimens and long-acting formulation drugs in HIV therapy. Frontiers in Clinical Drug Research: HIV 2021; 5: 95-139.
[http://dx.doi.org/10.2174/9789811464454121050005]
[81]
Garland JM, Levinson A, Wing E. Care of critically ill patients with human immunodeficiency virus. Ann Am Thorac Soc 2020; 17(6): 659-69.
[http://dx.doi.org/10.1513/AnnalsATS.201909-694CME] [PMID: 32216642]
[82]
Crutchley RD, Cheng A, Guduru R. Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection. HIV AIDS (Auckl) 2016; 8: 47-65.
[http://dx.doi.org/10.2147/HIV.S99063] [PMID: 27022304]
[83]
Giguère P, Nhean S, Tseng AL, Hughes CA, Angel JB. Getting to the heart of the matter: A review of drug interactions between HIV antiretrovirals and cardiology medications. Can J Cardiol 2019; 35(3): 326-40.
[http://dx.doi.org/10.1016/j.cjca.2018.12.020] [PMID: 30825953]
[84]
Dionne B. Key principles of antiretroviral pharmacology. Infectious Disease Clinics 2019; 33(3): 787-805.
[PMID: 31395145]
[85]
Tseng A, Hughes CA, Wu J, Seet J, Phillips EJ. Cobicistat versus ritonavir: Similar pharmacokinetic enhancers but some important differences. Ann Pharmacother 2017; 51(11): 1008-22.
[http://dx.doi.org/10.1177/1060028017717018] [PMID: 28627229]
[86]
Khan MM. Acquired immune deficiency syndrome. Immunobiology: The immune system in health and disease. (5th ed.). New York: Garland Science 2001; pp. 293-330.
[87]
Glassman R, Berry M, Libman PH. Primary care HIV manual September, 2020. 2020. Available From: https://aidsetc.org/topic/hiv-primary-care
[88]
Melissa EB. HIV Treatment and prophylaxis. Pharmacy Tech topics 2020; 25(4): 1-24.
[89]
Datta S, Kumar U. Human immunodeficiency virus and contraception. Mind the gaps: Cases in gynaecology Sexual and reproductive health. Amsterdam: Elsevier 2021; p. 165.
[90]
Gutierrez MM, Mateo MG, Corbacho N, Vidal F, Domingo P. Drug-drug interactions when treating HIV-related metabolic disorders. Expert Opin Drug Metab Toxicol 2019; 15(10): 787-802.
[http://dx.doi.org/10.1080/17425255.2019.1667334] [PMID: 31512529]
[91]
Gellissen R. Case study: Battle of the CQUINS. HIV Nursing 2017; 17(4): 145-7.
[92]
Pett SL, Emery S. AtazanavirKucers’ The Use of Antibiotics. United States: CRC Press 2017; pp. 4142-55.
[93]
Agency EM. Important medical event terms list version (MedDRA)–version 24.0. 2021. Available From: https://www.alims.gov.rs/wp-content/uploads/2022/02/IME_list_version_241.pdf

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy