{"id":5309,"date":"2021-12-13T18:02:30","date_gmt":"2021-12-13T15:02:30","guid":{"rendered":"https:\/\/www.klimik.org.tr\/koronavirus\/?p=5309"},"modified":"2021-12-23T21:08:57","modified_gmt":"2021-12-23T18:08:57","slug":"eriskinlerde-covid-19un-anti-viral-tedavisi","status":"publish","type":"post","link":"https:\/\/www.klimik.org.tr\/koronavirus\/eriskinlerde-covid-19un-anti-viral-tedavisi\/","title":{"rendered":"KL\u0130M\u0130K Derne\u011fi&#8217;nden Eri\u015fkinlerde COVID-19\u2019un Antiviral Tedavisi \u0130\u00e7in \u00d6neriler (G\u00fcncelleme Tarihi: 23.12.2021)"},"content":{"rendered":"<p><img decoding=\"async\" loading=\"lazy\" class=\"alignnone wp-image-5416 size-full\" src=\"https:\/\/www.klimik.org.tr\/koronavirus\/wp-content\/uploads\/2021\/12\/Tablo-2-2.jpg\" alt=\"\" width=\"2162\" height=\"2410\" \/><div id=\"accordions-5310\" class=\"accordions-5310 accordions\" data-accordions={&quot;lazyLoad&quot;:true,&quot;id&quot;:&quot;5310&quot;,&quot;event&quot;:&quot;click&quot;,&quot;collapsible&quot;:&quot;true&quot;,&quot;heightStyle&quot;:&quot;content&quot;,&quot;animateStyle&quot;:&quot;swing&quot;,&quot;animateDelay&quot;:1000,&quot;navigation&quot;:true,&quot;active&quot;:999,&quot;expandedOther&quot;:&quot;no&quot;}>\n                <div id=\"accordions-lazy-5310\" class=\"accordions-lazy\" accordionsId=\"5310\">\n                    <\/div>\n\n    <div class=\"items\"  style=\"display:none\" >\n    \n            <div post_id=\"5310\" itemcount=\"0\"  header_id=\"header-1600776266850\" id=\"header-1600776266850\" style=\"\" class=\"accordions-head head1600776266850 border-none\" toggle-text=\"\" main-text=\"G\u0130R\u0130\u015e\">\n                                    <span id=\"accordion-icons-1600776266850\" class=\"accordion-icons\">\n                        <span class=\"accordion-icon-active accordion-plus\"><i class=\"fas fa-chevron-up\"><\/i><\/span>\n                        <span class=\"accordion-icon-inactive accordion-minus\"><i class=\"fas fa-chevron-right\"><\/i><\/span>\n                    <\/span>\n                    <span id=\"header-text-1600776266850\" class=\"accordions-head-title\">G\u0130R\u0130\u015e<\/span>\n                            <\/div>\n            <div class=\"accordion-content content1600776266850 \">\n                <p>COVID-19 patogenezinde erken d\u00f6nemde virusun, sonras\u0131ndaysa konak savunmas\u0131n\u0131n rol ald\u0131\u011f\u0131 bilinmektedir. Bu nedenle g\u00fcn\u00fcm\u00fczde COVID-19 tedavisinde hastal\u0131\u011f\u0131n ilk 7-10 g\u00fcn\u00fcnde virusun kendisi veya konak h\u00fccredeki \u00e7o\u011falma s\u00fcre\u00e7leri; 7-10 g\u00fcnden sonraysa virusa kar\u015f\u0131 kona\u011f\u0131n verdi\u011fi dengesiz ba\u011f\u0131\u015f\u0131k yan\u0131t ve bunun sonucunda geli\u015fen hiperinflamasyon ve koag\u00fclasyon sistemlerini hedefleyen ajanlar kullan\u0131lmaktad\u0131r. Anti-viral tedavilerin COVID-19\u2019un\u00a0 erken d\u00f6neminde, yani hastal\u0131\u011f\u0131n hen\u00fcz hafif -orta semptomlarla seyretti\u011fi evrede\u00a0 etkili olmas\u0131 beklenmektedir (<span style=\"color: #ff0000;\"><a style=\"color: #ff0000;\" href=\"https:\/\/www.klimik.org.tr\/koronavirus\/wp-content\/uploads\/2021\/12\/Tablo1.pdf\" target=\"_blank\" rel=\"noopener\">Tablo1<\/a><\/span>).<\/p>\n<p>Virusun kendisini veya konak h\u00fccresinde \u00e7o\u011falmas\u0131n\u0131 inhibe etmek amac\u0131yla \u00e7al\u0131\u015f\u0131lm\u0131\u015f veya halen \u00e7al\u0131\u015fmas\u0131 devam eden \u00e7ok say\u0131da ila\u00e7 bulunmaktad\u0131r. Virus ve virusun h\u00fccrede \u00e7o\u011falma s\u00fcreci daha iyi anla\u015f\u0131ld\u0131k\u00e7a etkili olabilecek ba\u015fka ila\u00e7 \u00e7al\u0131\u015fmalar\u0131 da g\u00fcndeme gelmektedir. Bu ila\u00e7lar esas olarak\u00a0 SARS-CoV-2 proteinlerini hedefleyenler ve SARS-CoV-2\u2019nin konak h\u00fccresinde \u00e7o\u011falmas\u0131na yard\u0131m eden konak proteinlerini hedefleyenler olarak iki gruba ayr\u0131labilir.<\/p>\n<p>Burada SARS-CoV-2\u2019yi hedefleyen tedaviler i\u00e7inde yer alan, SARS-CoV-2\u2019nin spike proteinini hedefleyen konvalesan plazma ve monoklonal antikorlar, SARS-CoV-2\u2019nin RNA\u2019ya ba\u011f\u0131ml\u0131 RNA polimeraz\u0131n\u0131 hedefleyen favipiravir, remdesivir ve molnupiravir ve SARS-CoV-2\u2019nin ana proteaz\u0131n\u0131 hedefleyen pakslovid\u2019in (PF- 07321332) COVID-19\u2019daki etkinli\u011fi konusundaki g\u00fcncel geli\u015fmeler \u00a0\u00f6zetlenerek, mevcut kan\u0131tlarla \u00f6nerilerde bulunulacakt\u0131r (<span style=\"color: #ff0000;\"><a style=\"color: #ff0000;\" href=\"https:\/\/www.klimik.org.tr\/koronavirus\/wp-content\/uploads\/2021\/12\/Tablo-2-2.jpg\" target=\"_blank\" rel=\"noopener\">Tablo 2<\/a><\/span>).<\/p>\n<p>Metinde ge\u00e7en, \u201cA\u011f\u0131r COVID-19 a\u00e7\u0131s\u0131ndan risk yaratan durumlar ve hastal\u0131klar\u201d \u015funlard\u0131r:<\/p>\n<ul>\n<li><strong>Ya\u015fl\u0131l\u0131k (<\/strong>\u226565 ya\u015f)<\/li>\n<li>Gebelik<\/li>\n<li>Ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 bask\u0131layan hastal\u0131k varl\u0131\u011f\u0131 veya ila\u00e7 kullan\u0131m\u0131<\/li>\n<li>Diabetes mellitus<\/li>\n<li>Obezite (VK\u0130 >30kg\/m<sup>2<\/sup>)<\/li>\n<li>Kronik b\u00f6brek yetmezli\u011fi<\/li>\n<li>Kronik karaci\u011fer hastal\u0131\u011f\u0131 (siroz)<\/li>\n<li>Hipertansiyon (pregestasyonel veya gestasyonel)<\/li>\n<li>Di\u011fer kardiovask\u00fcler hastal\u0131klar (konjenital kalp hastal\u0131klar\u0131, kapak hst dahil)<\/li>\n<li>Kronik akci\u011fer hastal\u0131klar\u0131 (\u00f6rn.KOAH, orta-a\u011f\u0131r \u015fiddetli ast\u0131m, kistik fibroz, interstisyel akci\u011fer hastal\u0131\u011f\u0131, pulmoner hipertansiyon)<\/li>\n<li>Orak h\u00fccreli anemi<\/li>\n<li>N\u00f6rolojik geli\u015fimsel hastal\u0131klar (\u00f6rn.serebral palsi)<\/li>\n<li>Down sendromu<\/li>\n<li>Di\u011fer t\u0131bbi kompleks durumlar\u0131 (\u00f6rn.genetik veya metabolik sendromlar veya a\u011f\u0131r konjental anomaliler)<\/li>\n<li>Medikal teknolojik destek alanlar (trakeostomi, gastrostomi, solunum deste\u011fi vb)<\/li>\n<\/ul>\n            <\/div>\n    \n            <div post_id=\"5310\" itemcount=\"1\"  header_id=\"header-1600776373704\" id=\"header-1600776373704\" style=\"\" class=\"accordions-head head1600776373704 border-none\" toggle-text=\"\" main-text=\"KONVALESAN PLAZMA\">\n                                    <span id=\"accordion-icons-1600776373704\" class=\"accordion-icons\">\n                        <span class=\"accordion-icon-active accordion-plus\"><i class=\"fas fa-chevron-up\"><\/i><\/span>\n                        <span class=\"accordion-icon-inactive accordion-minus\"><i class=\"fas fa-chevron-right\"><\/i><\/span>\n                    <\/span>\n                    <span id=\"header-text-1600776373704\" class=\"accordions-head-title\">KONVALESAN PLAZMA<\/span>\n                            <\/div>\n            <div class=\"accordion-content content1600776373704 \">\n                <p>Toplam 11782 hasta i\u00e7eren on randomize kontroll\u00fc \u00e7al\u0131\u015fman\u0131n meta-analizinde, COVID-19\u2019dan iyile\u015fmi\u015f hastalardan elde edilen konvalesan plazma uygulamas\u0131n\u0131n, COVID-19 hastalar\u0131nda mortalite (RR:1.02 , %95CI:0.92 -1.12), hastane yat\u0131\u015f s\u00fcresi (HR:1.07, %95CI:0.79 \u2013 1.45), mekanik ventilasyon s\u00fcresi \u00a0(RR:0.81, %95CI:0.42 -1.58)\u00a0 \u00fczerine olumlu bir etkisinin olmad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (1). Ancak bir randomize kontroll\u00fc (2) ve bir g\u00f6zlemsel \u00e7al\u0131\u015fmada (3), y\u00fcksek anti-SARS-CoV-2 S antikoru olan don\u00f6rden, ilk 3-5 g\u00fcnde verilmesi halinde konvalesan plazma tedavisinin etkili olabilece\u011fine dair veriler elde edilmesiyle, bu konuda ek \u00e7al\u0131\u015fmalar\u0131n gerekti\u011fi d\u00fc\u015f\u00fcn\u00fclm\u00fc\u015ft\u00fcr. Bunu izleyen s\u00fcre\u00e7te a\u011f\u0131r COVID-19 riski olan, >50 ya\u015f, ayaktan izlenen 511 COVID-19 hastas\u0131nda yap\u0131lan randomize,\u00a0 plasebo kontroll\u00fc bir \u00e7al\u0131\u015fmada, erken d\u00f6nemde (semptom s\u00fcresi ortalama 4 g\u00fcn), y\u00fcksek\u00a0 antikor titreli\u00a0 konvalesan plazma (ortalama n\u00f6tralizan antikor titresi 1\/641) kullan\u0131m\u0131n\u0131n, hastal\u0131\u011f\u0131n ilerlemesi anlam\u0131nda bir fark yaratmad\u0131\u011f\u0131 (%30\u2019a kar\u015f\u0131l\u0131k\u00a0 %31.9) \u00a0g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (4). Bu verilerle DS\u00d6, COVD-19 tedavisi amac\u0131yla konvalesan plazma kullan\u0131lmamas\u0131n\u0131 \u00f6nermi\u015ftir (5).<\/p>\n<p><strong><em>\u00d6neri <\/em><\/strong><\/p>\n<p><strong><em>Yap\u0131lan \u00e7ok say\u0131da randomize kontroll\u00fc \u00e7al\u0131\u015fmada COVID-19 tedavisinde konvalesan plazma tedavisinin, erken d\u00f6nemde ve y\u00fcksek antikor titresi i\u00e7eren plazma uygulamas\u0131 dahil olmak \u00fczere, etkisiz oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu nedenle\u00a0 COVID-19 tedavisi amac\u0131yla konvalesan plazma kullan\u0131m\u0131 \u00f6nerilmemektedir. <\/em><\/strong><\/p>\n<p><strong>Kaynaklar<\/strong><\/p>\n<ol>\n<li>Janiaud P, Axfors C, Schmitt AM, Gloy V, Ebrahimi F, Hepprich M, et al. Association of Convalescent Plasma Treatment With Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis. JAMA. 2021;325(12):1185-1195. doi: 10.1001\/jama.2021.2747. PMID: 33635310; PMCID: PMC7911095.<\/li>\n<li>Libster R, P\u00e9rez Marc G, Wappner D, Coviello S, Bianchi A, Braem V, et al. Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults. N Engl J Med. 2021;384(7):610-618. doi: 10.1056\/NEJMoa2033700. Epub 2021 Jan 6. PMID: 33406353; PMCID: PMC7793608.<\/li>\n<li>Joyner MJ, Carter RE, Senefeld JW, Klassen SA, Mills JR, Johnson PW, et al. Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19. N Engl J Med. 2021;384(11):1015-1027. doi: 10.1056\/NEJMoa2031893. Epub 2021 Jan 13. PMID: 33523609; PMCID: PMC7821984.<\/li>\n<li>Korley FK, Durkalski-Mauldin V, Yeatts SD, Schulman K, Davenport RD, Dumont LJ, El Kassar N, et al. Early Convalescent Plasma for High-Risk Outpatients with Covid-19. N Engl J Med. 2021;385(21):1951-1960. doi: 10.1056\/NEJMoa2103784. Epub 2021 Aug 18. PMID: 34407339; PMCID: PMC8385553.<\/li>\n<li><em>Therapeutics and COVID-19 WHO Living guideline; <\/em><a href=\"https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-therapeutics-2021.4\"><em>https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-therapeutics-2021.4<\/em><\/a><\/li>\n<\/ol>\n            <\/div>\n    \n            <div post_id=\"5310\" itemcount=\"2\"  header_id=\"header-1600777320887\" id=\"header-1600777320887\" style=\"\" class=\"accordions-head head1600777320887 border-none\" toggle-text=\"\" main-text=\"SARS-COV-2\u2019YE \u00d6ZG\u00dc MONOKLONAL ANT\u0130KORLAR\">\n                                    <span id=\"accordion-icons-1600777320887\" class=\"accordion-icons\">\n                        <span class=\"accordion-icon-active accordion-plus\"><i class=\"fas fa-chevron-up\"><\/i><\/span>\n                        <span class=\"accordion-icon-inactive accordion-minus\"><i class=\"fas fa-chevron-right\"><\/i><\/span>\n                    <\/span>\n                    <span id=\"header-text-1600777320887\" class=\"accordions-head-title\">SARS-COV-2\u2019YE \u00d6ZG\u00dc MONOKLONAL ANT\u0130KORLAR<\/span>\n                            <\/div>\n            <div class=\"accordion-content content1600777320887 \">\n                <p>Bu ajanlarla,\u00a0 \u00e7ok say\u0131da hasta i\u00e7eren, randomize \u00e7ift-k\u00f6r\u00a0 plasebo kontroll\u00fc, genel olarak eri\u015fkinlerde yap\u0131lan\u00a0 \u00e7al\u0131\u015fmalarda \u015fu sonu\u00e7lar elde edilmi\u015ftir :<\/p>\n<p><strong>Ayaktan izlenen hastalar\u0131n tedavisinde:<\/strong> Hastal\u0131\u011f\u0131n\u0131n ilk 7-10 g\u00fcn\u00fcnde olan ve a\u011f\u0131r hastal\u0131k i\u00e7in risk fakt\u00f6r\u00fc bulunan COVID-19 hastalar\u0131nda\u00a0 \u0130V yoldan uygulanan bamlavinimab\/etesevimab, kasirivimab\/imdevimab (subkutan da uygulanab\u015flmektedir), sotrovimab, regdenvimab ve BRII-196\/BRII-198\u00a0 isimli SARS-CoV-2\u2019ye \u00f6zg\u00fc monoklonal antikorlar\u0131n \u00f6l\u00fcm ve hastane yat\u0131\u015f\u0131n\u0131 >%70-85 azaltt\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (1-6). Ayaktan izlenen, %90\u2019\u0131 a\u011f\u0131r hastal\u0131k i\u00e7in riskli, hafif\/orta seyirli semptomatik COVID-19 hastalar\u0131n\u0131n tedavisinde de intramuskuler yoldan verilen tiksagevimab\/silgavimab\u0131n hastane yat\u0131\u015f\u0131 ve \u00f6l\u00fcm\u00fc, semptomlar\u0131n ilk 5 g\u00fcn\u00fcnde verildi\u011finde %67, ilk 7 g\u00fcnde verildi\u011findeyse %50 oran\u0131nda azaltt\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (7).<\/p>\n<p><strong>Hastanede yatan hastalar\u0131n tedavisinde:<\/strong> Oksijen almayan veya d\u00fc\u015f\u00fck ak\u0131mda alan ve seronegatif\u00a0 olan COVID-19 hastalar\u0131nda kasirivimab-imdevimab\u0131n \u00f6l\u00fcm-mekanik ventilasyonu\u00a0 %47 azaltt\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (8).<\/p>\n<p><strong>Temas sonras\u0131 profilakside:<\/strong> Ev i\u00e7i temastan sonraki ilk 96 saatte ba\u015fvuranlarda subkutan uygulanan kasirivimab-imdevimab\u0131n semptomatik hastal\u0131\u011f\u0131 %92 azaltt\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (9).<\/p>\n<p><strong>Temas \u00f6ncesi profilakside:<\/strong> SARS-CoV-2 ge\u00e7irmemi\u015f, a\u015f\u0131s\u0131z, a\u015f\u0131 yan\u0131t\u0131n\u0131n yetersiz olma riski veya SARS-CoV-2 temas riski y\u00fcksek eri\u015fkinlerde\u00a0 intramusk\u00fcler uygulanan, uzun etkili tiksagevimab<strong>-<\/strong>silgavimab kombinasyonunun ilk 6 ayda\u00a0 SARS-CoV-2 RT-PCR-pozitif semptomatik hastal\u0131\u011f\u0131 %77 azaltt\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir (10).<\/p>\n<p>COVID-19 tedavisi i\u00e7in kan\u0131ta dayal\u0131 \u00f6neriler sunan ABD NIH, IDSA ve ESCMID rehberleri\u2019nde hafif-orta seyirli COVID-19 nedeniyle ayaktan izlenen ve a\u011f\u0131r hastal\u0131\u011fa ilerleme riski y\u00fcksek olan hastalarda\u00a0 bamlavinimab\/etesevimab, kasirivimab\/imdevimab veya sotrovimab tedavileri \u00f6nerilmektedir. Yine yatan, a\u011f\u0131r hastal\u0131k riski bulunan seronegatif hastalara kasirivimab-imdevimab \u00f6nerilmi\u015ftir (11-14).\u00a0\u00a0 A\u011f\u0131r hastal\u0131\u011fa ilerleme riski y\u00fcksek olan gruplar i\u00e7inde il<strong>eri ya\u015f (<\/strong>\u226565), obezite (eri\u015fkinde BMI >25 kg\/m<sup>2<\/sup>, 12-17 ya\u015f aras\u0131nda BMI\u2019nin\u00a0 ya\u015f ve cinse g\u00f6re\u2265 85. persantil\u00a0 olmas\u0131), kronik b\u00f6brek yetmezli\u011fi, diabetes mellitus, ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 bask\u0131layan hastal\u0131k varl\u0131\u011f\u0131 veya ila\u00e7 kullan\u0131m\u0131\u00a0 , kardiovask\u00fcler hastal\u0131klar (konjenital kalp hastal\u0131klar\u0131 veya hipertansiyon dahil), kronik akci\u011fer hastal\u0131klar\u0131 (\u00f6rn.KOAH, orta-a\u011f\u0131r \u015fiddetli ast\u0131m, kistik fibroz, interstisyel akci\u011fer hastal\u0131\u011f\u0131, pulmoner hipertansiyon), n\u00f6rolojik geli\u015fimsel hastal\u0131klar (\u00f6rn.serebral palsi), orak h\u00fccreli anemi, di\u011fer t\u0131bbi kompleks durumlar (\u00f6rn.genetik veya metabolik sendromlar veya a\u011f\u0131r konjental anomaliler) ile birlikte gebelik de yer alm\u0131\u015ft\u0131r (12). Monoklonal antikor uygulamas\u0131n\u0131n yarar\u0131n\u0131 g\u00f6steren klinik \u00e7al\u0131\u015fmalarda tam temsil edilmemi\u015f olsalar da a\u011f\u0131r hastal\u0131k a\u00e7\u0131s\u0131ndan risk grubunda bulunmalar\u0131 nedeniyle gebelerde mAb tedavisine ABD FDA taraf\u0131ndan acil kullan\u0131m onay\u0131 verilmi\u015ftir. Bu ajanlar\u0131n, \u015fu ana kadar kullan\u0131lm\u0131\u015f oldu\u011fu gebelerdeki sonu\u00e7lar\u0131na bak\u0131larak da, gebelerde etkili ve g\u00fcvenli oldu\u011fu s\u00f6ylenebilir (16).<\/p>\n<p>Onay alm\u0131\u015f veya geli\u015ftirilmekte olan t\u00fcm mAb\u2019lar, S proteinin ACE-2 resept\u00f6r\u00fcne ba\u011flanan\u00a0 Resept\u00f6r Ba\u011flayan B\u00f6lgesini (RBD) hedeflemektedir. Bu nedenle virusun RBD\u2019sinde geli\u015fen mutasyonlar mAb\u2019lar\u0131n etkisini azaltabilir. Pandeminin ba\u015f\u0131ndan beri ba\u011f\u0131\u015f\u0131kl\u0131ktan ka\u00e7abilen SARS-CoV-2 varyantlar\u0131 ortaya \u00e7\u0131kmaktad\u0131r ve infeksiyon zinciri k\u0131r\u0131lmad\u0131k\u00e7a \u00e7\u0131kmaya da devam edecektir. Bu durumun mAb tedavileri \u00fczerine olumsuz etkisi olabilir. Bu nedenle bir \u00fclkede veya b\u00f6lgede kullan\u0131lacak mAb\u2019lara karar verilirken, o b\u00f6lgede yayg\u0131n olan varyantlar\u0131n duyarl\u0131l\u0131\u011f\u0131n\u0131n da dikkate al\u0131nmas\u0131 \u00f6nerilmektedir. Ayn\u0131 nedenle RBD\u2019nin mutasyona kolay u\u011frayan b\u00f6lgerine kar\u015f\u0131 geli\u015ftirilen mAb\u2019lar tek ba\u015flar\u0131na de\u011fil ikili kombinasyonlar halinde kullan\u0131lmaktad\u0131r. Nitekim artm\u0131\u015f varyant direnci nedeniyle tek ba\u015f\u0131na bamlanivimab uyulamas\u0131n\u0131n acil kullan\u0131m onay\u0131 Nisan 2021\u2019de geri \u00e7ekilmi\u015ftir.\u00a0 Bununla birlikte \u00a0sotrovimab gibi \u00a0baz\u0131 mAb\u2019lar mutasyondan korunmu\u015f b\u00f6lgeleri hedef almalar\u0131 nedeniyle mevcut VOC\/VOI\u2019lere\u00a0 <em>in vitro <\/em>ve <em>in vivo<\/em>\u00a0 olarak etkilerini korumaktad\u0131rlar. Bu t\u00fcr mAb\u2019lar\u0131n kombinasyon halinde kullan\u0131lmas\u0131na da gerek olmad\u0131\u011f\u0131 bildirilmektedir.\u00a0 Ancak her durumda kullan\u0131mdaki mAb\u2019lara kar\u015f\u0131 dola\u015f\u0131mdaki varyantlarda diren\u00e7 geli\u015fimi yak\u0131ndan izlenmelidir (17).<\/p>\n<p>Var olan mAb\u2019lar i\u00e7inde \u00fclkemizde \u015fu anda bask\u0131n olan\u00a0 deltaya kar\u015f\u0131 etkinli\u011fini devam ettirenler bamlavinimab\/etesevimab, kasirivimab\/imdevimab,\u00a0 sotrovimab ve tiksagevimab \/silgavimabd\u0131r (18). Ancak yeni ortaya \u00e7\u0131kan omikron varyant\u0131n\u0131n, mAb\u2019lardan ka\u00e7abilece\u011fi kayg\u0131s\u0131 bulunmaktad\u0131r ve \u00f6zellikle bamlavinimab\/etesevimab, kasirivimab\/imdevimab\u0131n etkinli\u011finin ciddi \u015fekilde azalabilece\u011fi tahmin edilmekte, sotrovimab\u0131n ise etkinli\u011finin devam edece\u011fi \u00f6ng\u00f6r\u00fclmektedir.<\/p>\n<p>Monoklonal antikorlar\u0131n en \u00f6nemli dezavantajlar\u0131 genellikle \u0130V (baz\u0131lar\u0131n\u0131n \u0130M veya SC) uygulanmas\u0131, fiyatlar\u0131n\u0131n \u00e7ok y\u00fcksek olmas\u0131 ve d\u00fcnyada COVID-19\u2019un halen \u00e7ok fazla g\u00f6r\u00fcl\u00fcyor olmas\u0131 nedeniyle \u00fcretici firmalar\u0131n \u00fcr\u00fcnleri yeterli miktarda ve hemen sa\u011flayamamas\u0131d\u0131r.\u00a0 \u00dclkemizde hen\u00fcz bulunmayan ve kullan\u0131lamayan bu SARS-CoV-2\u2019ye mAb\u2019lara ula\u015f\u0131labilmesi, \u00f6zellikle riskli gruplarda \u00f6l\u00fcm oranlar\u0131n\u0131n azalt\u0131lmas\u0131na katk\u0131 sa\u011flayacakt\u0131r.<\/p>\n<p><strong><em>\u00d6neri<\/em><\/strong><\/p>\n<p><strong><em>Ayaktan izlenen veya ba\u015fka nedenlerle hastanede yatarken orta-hafif seyirli do\u011frulanm\u0131\u015f COVID-19 tan\u0131s\u0131 konulan, SARS-CoV-2\u2019ye kar\u015f\u0131 TAM A\u015eILAMASI YAPILMAMI\u015e ki\u015filerde, semptomlar\u0131n ba\u015flamas\u0131ndan itibaren \u0130LK 10 G\u00dcN \u0130\u00c7\u0130NDE, a\u015fa\u011f\u0131da tan\u0131mlanm\u0131\u015f R\u0130SK FAKT\u00d6RLER\u0130NDEN EN AZ B\u0130R\u0130N\u0130N OLMASI HAL\u0130NDE bamlanivimab\/etesevimab, kasirivimab\/imdevimab,\u00a0 sotrovimab ve onay almas\u0131 halinde<\/em><\/strong><strong>\u00a0 <\/strong><strong><em>tiksagevimab \/<\/em><\/strong><strong><em>silgavimab<\/em><\/strong><strong><em> tedavilerinden birinin uygulanmas\u0131 \u00f6nerilir. Kaynaklar\u0131n s\u0131n\u0131rl\u0131 olmas\u0131 halinde a\u015fa\u011f\u0131daki gruplar\u0131n s\u0131rayla \u00f6nceliklendirilmesi \u00f6nerilir. FDA, 3 Aral\u0131k itibariyle bebekler dahil olmak \u00fczere t\u00fcm ya\u015f gruplar\u0131nda kasirivimab\/imdevimab kullan\u0131m\u0131n\u0131 onaylam\u0131\u015f olmakla birlikte 18 ya\u015f alt\u0131nda olan y\u00fcksek riskli hastalarda mAb\u2019lar\u0131n etkinli\u011fi konusunda s\u0131n\u0131rl\u0131 veri vard\u0131r. <\/em><\/strong><\/p>\n<ol>\n<li><strong><em>Gebelik<\/em><\/strong><\/li>\n<li><strong><em>Ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 bask\u0131lanm\u0131\u015f ve a\u015f\u0131yla Anti-SARS-CoV-2 antikoru olu\u015fmad\u0131\u011f\u0131 g\u00f6sterilen hastalar (bu hastalarda ilk 10 g\u00fcn ko\u015fulu aranmaz)<\/em><\/strong><\/li>\n<li><strong><em>Ba\u011f\u0131\u015f\u0131kl\u0131\u011f\u0131 bask\u0131layan hastal\u0131k varl\u0131\u011f\u0131 veya ila\u00e7 kullan\u0131m\u0131 <\/em><\/strong><\/li>\n<li><strong><em>Ya\u015f <\/em><\/strong><strong><em>\u226565<\/em><\/strong><\/li>\n<li><strong><em>Di\u011fer komorbiditeleri olanlar<\/em><\/strong>\n<ol>\n<li><strong><em>Diabetes mellitus <\/em><\/strong><\/li>\n<li><strong><em>Obezite (<\/em><\/strong><strong><em>BMI >30kg\/m<sup>2<\/sup>)<\/em><\/strong><\/li>\n<li><strong><em>Kronik b\u00f6brek yetmezli\u011fi<\/em><\/strong><\/li>\n<li><strong><em>Hipertansiyon (pregestasyonel veya gestasyonel) <\/em><\/strong><\/li>\n<li><strong><em>Di\u011fer kardiovask\u00fcler hastal\u0131klar (konjenital kalp hastal\u0131klar\u0131, kapak hst. dahil) <\/em><\/strong><\/li>\n<li><strong><em>Kronik akci\u011fer hastal\u0131klar\u0131 (\u00f6rn.KOAH, orta-a\u011f\u0131r \u015fiddetli ast\u0131m, kistik fibroz, interstisyel akci\u011fer hastal\u0131\u011f\u0131, pulmoner hipertansiyon) <\/em><\/strong><\/li>\n<li><strong><em>Orak h\u00fccreli anemi <\/em><\/strong><\/li>\n<li><strong><em>N\u00f6rolojik geli\u015fimsel hastal\u0131klar (\u00f6rn.serebral palsi)<\/em><\/strong><\/li>\n<li><strong><em>Di\u011fer t\u0131bbi kompleks durumlar\u0131 (\u00f6rn.genetik veya metabolik sendromlar veya a\u011f\u0131r konjental anomaliler)<\/em><\/strong><\/li>\n<\/ol>\n<\/li>\n<\/ol>\n<p><strong>Kaynaklar<\/strong><\/p>\n<ol>\n<li><em>Chen P, Nirula A, Heller B, Gottlieb RL, Boscia J, et al. SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19. New England Journal of Medicine 2021;384(3):229-237. doi: 10.1056\/NEJMoa2029849.<\/em><\/li>\n<li><em>Investor\/Lilly. Lilly's bamlanivimab and etesevimab together reduced hospitalizations and death in Phase 3 trial for early COVID-19 Website <\/em><a href=\"https:\/\/investor.lilly.com\/news-releases\/news-release-details\/lillys-bamlanivimab-and-etesevimab-together-reduced\"><em>https:\/\/investor.lilly.com\/news-releases\/news-release-details\/lillys-bamlanivimab-and-etesevimab-together-reduced<\/em><\/a> <em>[accessed 16 June 2021].<\/em><\/li>\n<li><em>Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, et al. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. New England Journal of Medicine 2021;384(3):238-251. doi: 10.1056\/NEJMoa2035002. <\/em><\/li>\n<li><em>Gupta A, Gonzalez-Rojas Y, Juarez E, Casal MC, Moya J, at al. Covid-19 Treatment With SARS-CoV-2 Neutralizing Antibody Sotrovimab. medRxiv preprint 2021; doi: <\/em><a href=\"https:\/\/doi.org\/10.1101\/2021.05.27.21257096\"><em>https:\/\/doi.org\/10.1101\/2021.05.27.21257096<\/em><\/a><em>[accessed 16 June 2021].<\/em><\/li>\n<li><em>Ison MG<\/em><em>.<\/em><em> Therapeutic effect of regdanvimab in patients with mild to moderate COVID-19: Day 28 results of a multicenter, randomized, controlled, pivotal trial.<\/em><em> IDWeek 2021 Poster Session; September 29 \u2013October 3, 2021.<\/em><\/li>\n<li>O'Brien MP, Forleo-Neto E, Sarkar N, Isa F, Hou P, Chan KC, et al. Subcutaneous REGEN-COV Antibody Combination in Early SARS-CoV-2 Infection. medRxiv [Preprint]. 2021:2021.06.14.21258569. doi: 10.1101\/2021.06.14.21258569. PMID: 34159343; PMCID: PMC8219113.<\/li>\n<li><em>https:\/\/www.astrazeneca.com\/media-centre\/press-releases\/2021\/azd7442-phiii-trial-positive-in-covid-outpatients.html<\/em><\/li>\n<li><em>RECOVERY Collaborative Group. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. medRxiv preprint 2021; doi: https:\/\/doi.org\/10.1101\/2021.06.15.21258542.<\/em><em> [accessed 16 June 2021].<\/em><\/li>\n<li>O'Brien MP, Forleo-Neto E, Musser BJ, Isa F, Chan KC, Sarkar N, et al. Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19. N Engl J Med. 2021 ;385(13):1184-1195. doi: 10.1056\/NEJMoa2109682. Epub 2021 Aug 4. PMID: 34347950; PMCID: PMC8362593.<\/li>\n<li><em>Levin MJ.Phase 3 study of efficacy and safety of AZD7442 for pre-exposure prophylaxis of COVID-19 in adults. IDWeek 2021 ; Late Breaker Abstract 5; September 29 \u2013October 3, 2021<\/em><\/li>\n<li><em>COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https:\/\/www.covid19treatmentguidelines.nih.gov\/ <\/em><em>[accessed 16 September 2021]<\/em><\/li>\n<li><em>Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Infectious Diseases Society of America\u00a02021; Version 4.3.0. Website\u00a0<\/em><a href=\"https:\/\/www.idsociety.org\/practice-guideline\/covid-19-guideline-treatment-and-management\/\"><em>https:\/\/www.idsociety.org\/practice-guideline\/covid-19-guideline-treatment-and-management\/<\/em><\/a><em>. <\/em><em>[accessed 16 June 2021]<\/em><\/li>\n<li>Bartoletti M, Azap O, Barac A, Bussini L, Ergonul O, Krause R, et al. ESCMID COVID-19 Living guidelines: drug treatment and clinical management. Clin Microbiol Infect. 2021:S1198-743X(21)00634-0. doi: 10.1016\/j.cmi.2021.11.007. Epub ahead of print. PMID: 34823008; PMCID: PMC8606314.<\/li>\n<li><em>Therapeutics and COVID-19 WHO Living guideline; <\/em><a href=\"https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-therapeutics-2021.4\"><em>https:\/\/www.who.int\/publications\/i\/item\/WHO-2019-nCoV-therapeutics-2021.4<\/em><\/a><\/li>\n<li><em>https:\/\/www.fda.gov\/media\/145802\/download<\/em><\/li>\n<li><em>Thilagar BP,\u00a0 Ghosh AK,\u00a0\u00a0Nguyen J,\u00a0et <\/em><em>Outcomes of Anti-Spike Monoclonal Antibody Therapy in Pregnant Women with Mild to Moderate COVID-19. <\/em><em>medRxiv\u00a02021.11.27.21266942;\u00a0doi:\u00a0https:\/\/doi.org\/10.1101\/2021.11.27.2126694<\/em><\/li>\n<li>Corti D, Purcell LA, Snell G, Veesler D. Tackling COVID-19 with neutralizing monoclonal antibodies. Cell 2021;184(12):3086-3108. doi: 10.1016\/j.cell.2021.05.005<\/li>\n<li><a href=\"https:\/\/covdb.stanford.edu\/page\/susceptibility-data\/\"><em>https:\/\/covdb.stanford.edu\/page\/susceptibility-data\/<\/em><\/a><\/li>\n<\/ol>\n            <\/div>\n    \n            <div post_id=\"5310\" itemcount=\"3\"  header_id=\"header-1600777387000\" id=\"header-1600777387000\" style=\"\" class=\"accordions-head head1600777387000 border-none\" toggle-text=\"\" main-text=\"FAV\u0130P\u0130RAV\u0130R\">\n                                    <span id=\"accordion-icons-1600777387000\" class=\"accordion-icons\">\n                        <span class=\"accordion-icon-active accordion-plus\"><i class=\"fas fa-chevron-up\"><\/i><\/span>\n                        <span class=\"accordion-icon-inactive accordion-minus\"><i class=\"fas fa-chevron-right\"><\/i><\/span>\n                    <\/span>\n                    <span id=\"header-text-1600777387000\" class=\"accordions-head-title\">FAV\u0130P\u0130RAV\u0130R<\/span>\n                            <\/div>\n            <div class=\"accordion-content content1600777387000 \">\n                <p>Favipiravirin COVID-19\u2019da etkinli\u011fini ara\u015ft\u0131ran ve kar\u015f\u0131la\u015ft\u0131rma grubu olan 9 klinik \u00e7al\u0131\u015fman\u0131n (8\u2019i randomize kontroll\u00fc) meta-analizinde, favipiravir grubunda 7.g\u00fcnde klinik iyile\u015fmenin belirgin olarak daha fazla (RR:1.24, 95%CI: 1.09-1.41; P=0.001) oldu\u011fu g\u00f6r\u00fclm\u00fc\u015f; istatistiksel olarak anlaml\u0131 olmamakla birlikte 14.g\u00fcndeki viral klirens oranlar\u0131n\u0131n daha y\u00fcksek\u00a0 (RR:1.11, %95CI: 0.98-1.25; P=0.094);\u00a0 oksijen gereksiniminin %7 daha az (RR:0.93, %95CI: 0.67-1.28; P=0.664) ve mortalitenin %30 daha d\u00fc\u015f\u00fck (RR:0.709, %95CI: 0.262-1.920, P=0.499) oldu\u011fu belirlenmi\u015ftir (1). K\u0131sa s\u00fcre \u00f6nce yay\u0131mlanm\u0131\u015f ve kar\u015f\u0131la\u015ft\u0131rma grubu olan 12 \u00e7al\u0131\u015fman\u0131n dahil edildi\u011fi\u00a0 bir di\u011fer meta-analiz \u00e7al\u0131\u015fmas\u0131nda da\u00a0 COVID-19 hastalar\u0131nda favipiravirin \u00f6l\u00fcm\u00fc ve mekanik ventilasyon gereksinimini azaltmad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (2).<\/p>\n<p>Ancak her iki meta-analize dahil edilen \u00e7al\u0131\u015fmalar\u0131n tasar\u0131mlar\u0131, \u00e7al\u0131\u015fmada kar\u015f\u0131la\u015ft\u0131r\u0131lan ajanlar olduk\u00e7a farkl\u0131d\u0131r, randomize \u00e7al\u0131\u015fmalar a\u00e7\u0131k etiketlidir ve plasebo kontroll\u00fc de\u011fildir, \u00e7al\u0131\u015fmalara al\u0131nm\u0131\u015f hasta gruplar\u0131 da heterojendir, t\u00fcm bu nedenlerle favipiravirin COVID-19 tedavisindeki yerinin belirlenmesini sa\u011flamak \u00fczere \u00e7ift k\u00f6r, randomize, plasebo kontroll\u00fc \u00e7al\u0131\u015fmalar gerekmektedir.<\/p>\n<p>Yukar\u0131da belirtilmi\u015f \u00e7al\u0131\u015fmalara ek olarak Japonya\u2019da \u00fcretici firman\u0131n yapt\u0131\u011f\u0131 plasebo kontroll\u00fc, tek k\u00f6r Faz-3 \u00e7al\u0131\u015fmas\u0131nda a\u011f\u0131r olmayan pn\u00f6monili 156 COVID-19 olgusunda\u00a0 SARS-CoV-2 viral klirensi, favipiravir grubu i\u00e7in 11.9 g\u00fcnken, placebo grubu i\u00e7in 14.7 olarak belirlenmi\u015f ve aradaki fark istatistiksel olarak anlaml\u0131 bulunmu\u015ftur (P = 0.013) (3). Ancak bu sonu\u00e7lar\u0131 Aral\u0131k 2020\u2019de de\u011ferlendiren Japon \u0130la\u00e7 ve T\u0131bbi\u00a0 Cihaz Kurumu (PMDA), ek de\u011ferlendirmelere gereksinim oldu\u011funu bildirerek favipiravirn Japonya\u2019da COVID-19 tedavisinde kullan\u0131m\u0131na onay vermemi\u015ftir. Onay vermeme nedenleri olarak; bu Faz-3 \u00e7al\u0131\u015fmas\u0131n\u0131n sonlan\u0131m noktas\u0131 olan \u201csemptomlar\u0131n iyile\u015fmesi\u201d nin de\u011ferlendirilmesinin \u00a0subjektiviteden etkilenme potansiyeli ta\u015f\u0131mas\u0131, tasar\u0131m\u0131n\u0131n tek-k\u00f6r olmas\u0131 ve\u00a0 gruplar aras\u0131nda yanl\u0131l\u0131\u011f\u0131n\u00a0 etkinli\u011fi g\u00f6stermek a\u00e7\u0131s\u0131ndan \u00e7ok sorunlu olmas\u0131n\u0131 belirtmi\u015flerdir. Kurul, \u00fclkede yap\u0131lan klinik \u00e7al\u0131\u015fman\u0131n verilerinin yetersiz olmas\u0131 nedeniyle Kuveyt ve ABD\u2019de devam eden klinik \u00e7al\u0131\u015fmalar\u0131n sonu\u00e7lar\u0131na g\u00f6re onay\u0131n tekrar de\u011ferlendirilmesini uygun bulmu\u015ftur (4).\u00a0 Kuveyt\u2019te devam eden \u00e7ift-k\u00f6r faz-3 \u00e7al\u0131\u015fman\u0131n 353 hastay\u0131 i\u00e7eren ve 27 Ocak 2021\u2019de yap\u0131lan ara analizinde, favipiravir ve plasebo gruplar\u0131 aras\u0131nda\u00a0 primer sonlan\u0131m a\u00e7\u0131s\u0131ndan (hipoksinin d\u00fczelme s\u00fcresi) istatistiksel olarak anlaml\u0131 bir fark bulunmam\u0131\u015f\u00a0 (7 vs. 8 g\u00fcn, P > 0.05)\u00a0 ve \u00e7al\u0131\u015fman\u0131n bu nedenle sonland\u0131r\u0131ld\u0131\u011f\u0131 duyurulmu\u015ftur. Bu \u00e7al\u0131\u015fman\u0131n, 181 a\u011f\u0131r olmayan\u00a0 hastay\u0131 (ba\u015fvuruda NEWS skoru d\u00fc\u015f\u00fck olan) i\u00e7eren alt grup analizlerinde favipiravir verilenlerde taburculuk s\u00fcresi 8 g\u00fcnken, plasebo grubunda 11 g\u00fcn oldu\u011fu (P=0.006) g\u00f6r\u00fclerek, favipiravirin COVID-19 hastalar\u0131nda erken ba\u015flanmas\u0131n\u0131n yararl\u0131 olaca\u011f\u0131 ve ge\u00e7 evrelerde ba\u015fland\u0131\u011f\u0131nda etkili olmayaca\u011f\u0131 hipotezinin desteklendi\u011fi bildirilmi\u015ftir (5).<\/p>\n<p>Favipirivirin COVID-19\u2019daki etkinli\u011fini ara\u015ft\u0131ran yukar\u0131da \u00f6zetlenmi\u015f \u00e7al\u0131\u015fmalara g\u00f6re \u00e7ok daha g\u00fc\u00e7l\u00fc kan\u0131tlar sa\u011flayacak olan ve \u00a0Apiili Therapeutics sponsorlu\u011funda ABD, Meksika ve Brezilya\u2019da y\u00fcr\u00fct\u00fclen PRESECO \u00e7al\u0131\u015fmas\u0131n\u0131n sonu\u00e7lar\u0131 12 Kas\u0131m 2021 tarihinde a\u00e7\u0131klanm\u0131\u015ft\u0131r (6): \u00a0Bu \u00e7al\u0131\u015fma. favipiravirin, ayaktan hafif-orta COVID-19 hastalar\u0131nda etkinli\u011fini ara\u015ft\u0131ran randomize, \u00e7ift k\u00f6r,\u00a0 plasebo kontroll\u00fc bir faz-3 \u00e7al\u0131\u015fmas\u0131 olup, \u00e7al\u0131\u015fmaya dahil edilen 1231 hastada\u00a0 favipiravirin\u00a0 klinik iyile\u015fme s\u00fcresi \u00fczerine anlaml\u0131 bir etkisinin olmad\u0131\u011f\u0131 bildirilmi\u015ftir.<\/p>\n<p>K\u0131sa s\u00fcre \u00f6nce yay\u0131mlanm\u0131\u015f a\u00e7\u0131k etiketli, bir di\u011fer randomize klinik \u00e7al\u0131\u015fmada da, Malezya\u2019da 14 hastanede izlenmi\u015f \u226550 ya\u015f,\u00a0 \u22651 komorbiditesi olan ve hastal\u0131\u011f\u0131n\u0131n ilk 7 g\u00fcn\u00fcnde hastaneye yat\u0131r\u0131lm\u0131\u015f 500 hafif\/orta (oksijen almayan hastalar) COVID-19 hastas\u0131nda hipoksik olma, mekanik ventilasyon veya YB\u00dc\u2019ye gereksinim duyma ve \u00f6l\u00fcm oranlar\u0131, favipiravir alan ve almayan hastalar aras\u0131nda farkl\u0131 bulunmam\u0131\u015ft\u0131r (7).<\/p>\n<p>Son olarak favipiravir ayaktan izlenen, a\u011f\u0131r hastal\u0131k riski bulunan ki\u015filerdeki COVID-19\u2019un tedavisinde, PRINCIPLE (The Platform Randomised trial of Interventions Against COVID-19 In Older People) \u00e7al\u0131\u015fmas\u0131n\u0131n bir kolu olarak denenmektedir.\u00a0 Bu \u00e7al\u0131\u015fman\u0131n sonu\u00e7lar\u0131n\u0131n y\u0131l sonuna kadar a\u00e7\u0131klanmas\u0131 beklenmektedir (8).<\/p>\n<p><strong>\u00d6neri<\/strong><\/p>\n<p><strong><em>K\u0131sa s\u00fcre \u00f6nce sonu\u00e7lar\u0131 a\u00e7\u0131klanm\u0131\u015f ve yay\u0131mlanm\u0131\u015f randomize\u00a0 kontroll\u00fc \u00e7al\u0131\u015fmalar\u0131n sonu\u00e7lar\u0131yla birlikte, favipiravirin COVID-19\u2019da \u00f6l\u00fcm\u00fc ve hastane yat\u0131\u015f\u0131n\u0131 azaltma gibi \u00f6nemli klinik sonu\u00e7lara istenen etkinli\u011finin olmad\u0131\u011f\u0131 g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. Bu nedenle COVID-19 tedavisinde favipiravir rutin olarak kullan\u0131lmamal\u0131, \u00a0sadece farkl\u0131 doz se\u00e7eneklerini de i\u00e7eren,\u00a0 iyi tasarlanm\u0131\u015f klinik ara\u015ft\u0131rmalar kapsam\u0131nda kullan\u0131lmal\u0131d\u0131r. \u00a0<\/em><\/strong><\/p>\n<p><strong>Kaynaklar<\/strong><\/p>\n<ol>\n<li><em>Hassanipour S, Arab-Zozani M, Amani B, Heidarzad F, Fathalipour M, et al. The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials. Scientific Reports 2021;11:11022. doi: 10.1038\/s41598-021-90551-6.<br \/>\n<\/em><\/li>\n<li><em>\u00d6zl\u00fc\u015fen, B., Kozan, \u015e., Akcan, R.E.\u00a0et al.\u00a0Effectiveness of favipiravir in COVID-19: a live systematic review.\u00a0Eur J Clin Microbiol Infect Dis\u00a040,\u00a02575\u20132583 (2021). <\/em><a href=\"https:\/\/doi.org\/10.1007\/s10096-021-04307-1\"><em>https:\/\/doi.org\/10.1007\/s10096-021-04307-1<\/em><\/a><em>.<\/em><\/li>\n<\/ol>\n<ol>\n<li><em>FUJIFILM Toyama Chemical Co., Ltd. Anti- influenza drug Avigan\u00ae tablet meets primary endpoint in phase III clinical trial in Japan for COVID- 19 patients. , June 5, 2021. Website https:\/\/www.com\/jp\/en\/news\/hq\/5451?_ga=2.10224 8257.19488 31102.1612073055 - 48278 478.16120 73055.<\/em><em> [accessed 16 June 2021].<\/em><\/li>\n<li><em>Ueda M, Tanimoto T, Murayama A, Ozaki A, Kami M. Japan's Drug Regulation During the COVID-19 Pandemic: Lessons From a Case Study of Favipiravir. Clinical Pharmacological Therapy 2021. doi: 10.1002\/cpt.2251. <\/em><\/li>\n<li><em> Reddy\u2019s and GRA announce Avigan Pivotal Studies Update Study for hospitalized moderate to severe cases in Kuwait terminated, while study for out-patient mild to moderate cases continues in North America. June 5, 2021 . Website <\/em><a href=\"https:\/\/www.drreddys.com\/media\/928938\/2021-01-avigan-trial-update_v1.pdf\"><em>https:\/\/www.drreddys.com\/media\/928938\/2021-01-avigan-trial-update_v1.pdf<\/em><\/a><em>.<\/em><em> [accessed 16 June 2021].<\/em><\/li>\n<li><a href=\"https:\/\/www.appilitherapeutics.com\/newsfeed\/Appili-Therapeutics-Provides-Update-on-Phase-3-PRESECO-Clinical-Trial-Evaluating-Avigan%C2%AE%2FReeqonus%E2%84%A2\"><em>https:\/\/www.appilitherapeutics.com\/newsfeed\/Appili-Therapeutics-Provides-Update-on-Phase-3-PRESECO-Clinical-Trial-Evaluating-Avigan%C2%AE%2FReeqonus%E2%84%A2<\/em><\/a><em> .<\/em><em> [accessed 11 Dec 2021].<\/em><\/li>\n<li><em>Chuan Huan Chuah, Ting Soo Chow, Chee Peng Hor, Joo Thye Cheng, Hong Bee Ker, Heng Gee Lee, Kok Soon Lee, Noridah Nordin, Tiang Koi Ng, Masliza Zaid, Nor Zaila Zaidan, Suhaila Abdul Wahab, Nurul Ashikin Adnan, Noorlina Nordin, Tze Yuan Tee, Su Miin Ong, Suresh Kumar Chidambaram, Mahiran Mustafa, Malaysian Favipiravir Study Group, Efficacy of Early Treatment with Favipiravir on Disease Progression among High Risk COVID-19 Patients: A Randomized, Open-Label Clinical Trial,\u00a0Clinical Infectious Diseases, 2021; ciab962,\u00a0<\/em><a href=\"https:\/\/doi.org\/10.1093\/cid\/ciab962\"><em>https:\/\/doi.org\/10.1093\/cid\/ciab962<\/em><\/a><\/li>\n<li><em> Favipiravir to be investigated as a possible COVID-19 treatment for at-home recovery in the PRINCIPLE trial. 8 April 2021. Website <\/em><a href=\"https:\/\/www.principletrial.org\/news\/favipiravir-to-be-investigated-as-a-possible-covid-19-treatment-for-at-home-recovery-in-the-principle-trial\"><em>https:\/\/www.principletrial.org\/news\/favipiravir-to-be-investigated-as-a-possible-covid-19-treatment-for-at-home-recovery-in-the-principle-trial<\/em><\/a><em>. <\/em><em>[accessed 16 June 2021].<\/em><\/li>\n<\/ol>\n            <\/div>\n    \n            <div post_id=\"5310\" itemcount=\"4\"  header_id=\"header-1600777470625\" id=\"header-1600777470625\" style=\"\" class=\"accordions-head head1600777470625 border-none\" toggle-text=\"\" main-text=\"REMDESIVIR \">\n                                    <span id=\"accordion-icons-1600777470625\" class=\"accordion-icons\">\n                        <span class=\"accordion-icon-active accordion-plus\"><i class=\"fas fa-chevron-up\"><\/i><\/span>\n                        <span class=\"accordion-icon-inactive accordion-minus\"><i class=\"fas fa-chevron-right\"><\/i><\/span>\n                    <\/span>\n                    <span id=\"header-text-1600777470625\" class=\"accordions-head-title\">REMDESIVIR <\/span>\n                            <\/div>\n            <div class=\"accordion-content content1600777470625 \">\n                <p>Remdesivirin COVID-19 tedavisinde etkinli\u011fini ara\u015ft\u0131ran, 7333 hasta verisini i\u00e7eren 4 randomize kontroll\u00fc \u00e7al\u0131\u015fman\u0131n meta-analizinde, bu ilac\u0131n hastalarda mortaliteyi ve mekanik ventilasyon gereksinimini azaltmad\u0131\u011f\u0131 ve klinik iyile\u015fmeyi h\u0131zland\u0131rmad\u0131\u011f\u0131 sonucuna ula\u015f\u0131lm\u0131\u015ft\u0131r (1). Ancak mevcut verilerin kesin bir sonuca varabilmek i\u00e7in yeterli olmad\u0131\u011f\u0131 da belirtilmi\u015ftir. Bu nedenlerle remdesivirin COVID-19\u2019daki kullan\u0131m\u0131 konusunda da bir uzla\u015f\u0131ya var\u0131lamam\u0131\u015f, DS\u00d6 hastaneye yatan hastalarda remdesivir kullan\u0131m\u0131n\u0131 \u00f6nermezken, ABD IDSA ve NIH rehberleri oksijen ihtiyac\u0131 olup, mekanik ventilasyon deste\u011fi gerekmeyen yatan hastalarda 5 g\u00fcnl\u00fck IV remdesivir tedavisi \u00f6nermektedir (2, 3). Asl\u0131nda IDSA\u2019n\u0131n analizlerinde de remdesivirin hastalar\u0131n 28. G\u00fcn\u00fcndeki klinik iyile\u015fme ve mortalite oranlar\u0131 (RR:0.92; %95CI: 0.77-1.10) \u00fczerine \u00f6nemli bir etkisinin olmad\u0131\u011f\u0131\u00a0 \u00a0\u00a0g\u00f6zlenmi\u015f olmakla birlikte, remdesivir alan hastalarda 28.g\u00fcnde klinik iyile\u015fmenin daha fazla olma e\u011filiminde oldu\u011fu\u00a0 (RR:1.13; % 95CI 0.91-1.41) ve ek olarak a\u011f\u0131r COVID-19\u2019lu hastalar\u0131n post-hoc analizinde remdesivir alan hastalarda ortalama iyile\u015fme s\u00fcresinin k\u0131sald\u0131\u011f\u0131\u00a0 (ortanca 11\u2019e kar\u015f\u0131l\u0131k\u00a0 18 g\u00fcn; RR:1.31; 95%CI: 1.12-1.52) ve mekanik ventilasyona\u00a0 daha az gereksinim duyduklar\u0131\u00a0 (RR: 0.57; 95%CI: 0.42-0.79) g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (3).<\/p>\n<p>Remdesivir \u0130V yolla uyguland\u0131\u011f\u0131 i\u00e7in, yukar\u0131da s\u00f6z\u00fc edilen \u00e7al\u0131\u015fmalar\u0131n hepsinde hastaneye yat\u0131r\u0131lan, dolay\u0131s\u0131yla genellikle viral d\u00f6nemi ge\u00e7ip, immunolojik d\u00f6nemde bulunan a\u011f\u0131r\u00a0 hastalarda denenmi\u015ftir. Oysa antiviral ila\u00e7lar\u0131n, hastal\u0131\u011f\u0131n erken d\u00f6nemlerinde ba\u015flanmas\u0131 halinde etkili olmas\u0131 beklenmektedir. Bu nedenle ayaktan izlenen ve a\u011f\u0131r COVID-19 geli\u015fme riski olan 562 hastada, tedavinin hastal\u0131\u011f\u0131n ilk 3 g\u00fcn\u00fcnde ba\u015fland\u0131\u011f\u0131 randomize kontroll\u00fc bir \u00e7al\u0131\u015fmada, 28.g\u00fcnde \u00f6l\u00fcm veya hastaneye yat\u0131\u015f oran\u0131 remdesivir verilenlerde %0.7 iken plasebo verilenlerde %5.3 (p=0.008) bulunmu\u015ftur. Bu umut vadeden verilerden sonra Gilead remdesivirin oral formunu geli\u015ftirmek \u00fczere \u00e7al\u0131\u015fmalara ba\u015flam\u0131\u015ft\u0131r (4).<\/p>\n<p><strong><em>\u00d6neri<\/em><\/strong><\/p>\n<p><strong><em>Elde edilen veriler remdesivirin, COVID-19\u2019da erken d\u00f6nemde ba\u015fland\u0131\u011f\u0131nda etkili olabilece\u011fini d\u00fc\u015f\u00fcnd\u00fcrmektedir. Bu nedenle daha etkili olan monoklonal antikorlar veya a\u011f\u0131zdan al\u0131nabilecek \u00a0molnupiravir vb ajanlara ula\u015f\u0131lamamas\u0131 halinde ve semptomlar\u0131n ilk 7 g\u00fcn\u00fcnde olan, a\u011f\u0131r COVID-19 a\u00e7\u0131s\u0131ndan risk fakt\u00f6r\u00fc bulunan ki\u015filerde \u0130V remdesivir\u00a0 kullan\u0131lmas\u0131 \u00f6nerilir.<\/em><\/strong><\/p>\n<p><strong><em>\u00a0<\/em><\/strong><\/p>\n<p><strong>Kaynaklar<\/strong><\/p>\n<ol>\n<li><em>WHO, Therapeutics and COVID-19: living guideline - World Health Organization (WHO), 31 March 2021. <\/em><em>[accessed 16 June 2021].<\/em><\/li>\n<li><em>COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https:\/\/www.covid19treatmentguidelines.nih.gov\/ <\/em><em>[accessed 16 September 2021]<\/em><\/li>\n<li><em>Bhimraj A, Morgan RL, Shumaker AH, Lavergne V, Baden L, et al. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Infectious Diseases Society of America\u00a02021; Version 4.3.0. Website\u00a0<\/em><a href=\"https:\/\/www.idsociety.org\/practice-guideline\/covid-19-guideline-treatment-and-management\/\"><em>https:\/\/www.idsociety.org\/practice-guideline\/covid-19-guideline-treatment-and-management\/<\/em><\/a><em>. <\/em><em>[accessed 16 June 2021]<\/em><\/li>\n<li><em>Hill JA. Remdesivir for the treatment of high-risk non-hospitalized individuals with COVID-19: A randomized, double blind, placebo-controlled trial. <\/em><em>IDWeek 2021 ; Late Breaker Abstract 1; September 29 \u2013October 3, 2021<\/em><\/li>\n<li><em>Willyard C. Nature 2021; \u00a0<\/em><a href=\"https:\/\/doi.org\/10.1038\/d41586-021-02783-1\"><em>https:\/\/doi.org\/10.1038\/d41586-021-02783-1<\/em><\/a><\/li>\n<li>Gottlieb LG, Vaca CE, Paredes R, et al. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. New England Journal of Medicine2021; DOI: 10.1056\/NEJMoa2116846<\/li>\n<\/ol>\n            <\/div>\n    \n            <div post_id=\"5310\" itemcount=\"5\"  header_id=\"header-1600777496917\" id=\"header-1600777496917\" style=\"\" class=\"accordions-head head1600777496917 border-none\" toggle-text=\"\" main-text=\"MOLNUP\u0130RAV\u0130R \">\n                                    <span id=\"accordion-icons-1600777496917\" class=\"accordion-icons\">\n                        <span class=\"accordion-icon-active accordion-plus\"><i class=\"fas fa-chevron-up\"><\/i><\/span>\n                        <span class=\"accordion-icon-inactive accordion-minus\"><i class=\"fas fa-chevron-right\"><\/i><\/span>\n                    <\/span>\n                    <span id=\"header-text-1600777496917\" class=\"accordions-head-title\">MOLNUP\u0130RAV\u0130R <\/span>\n                            <\/div>\n            <div class=\"accordion-content content1600777496917 \">\n                <p>Molnupiravir (MK-4482\/EIDD-2801), n\u00fckleozid analo\u011fu olan N<sup>4<\/sup>-hidroksisitidin (NHC)\u2019in oral kullan\u0131labilen bir \u00f6n ilac\u0131d\u0131r. NHC\u2019nin RNA viruslar\u0131na kar\u015f\u0131 geni\u015f spektrumlu bir etkisi vard\u0131r ve <em>in-vitro<\/em> olarak Ebola virus, koronaviruslar, respiratuar sinsityum virusu (RSV) ve Venezuella at ensefaliti virusu (VEEV)\u2019na kar\u015f\u0131 etkili oldu\u011fu g\u00f6sterilmi\u015ftir. NHC varl\u0131\u011f\u0131nda farkl\u0131 viruslarla yap\u0131lan seri pasajlarda, bu ajan\u0131n diren\u00e7 bariyerinin y\u00fcksek oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr. NHC,\u00a0 SARS-CoV-2\u2019ye kar\u015f\u0131 Calu-3 ve insan hava yollar\u0131 h\u00fccrelerinde yap\u0131lan testlerde olduk\u00e7a etkili antiviral etkinlik g\u00f6stermi\u015f olup,\u00a0 IC50 de\u011ferleri\u00a0 s\u0131ras\u0131yla 0.08 mM ve 0.024 mM olarak belirlenmi\u015ftir. Ek olarak MERS-CoV, SARS-CoV ve SARS\u2019la ili\u015fkili di\u011fer zoonotik grup 2b ve 2c yarasa koronaviruslar\u0131na ve remdesivir diren\u00e7 mutasyonu ta\u015f\u0131yan koronaviruslara kar\u015f\u0131 da etkili oldu\u011fu g\u00f6sterilmi\u015ftir. Anti-viral etkinli\u011finin esas olarak viral \u00a0mutasyon s\u0131kl\u0131\u011f\u0131nda art\u0131\u015fa yol a\u00e7mas\u0131ndan kaynakland\u0131\u011f\u0131 bilinmektedir. Ger\u00e7ekle\u015fen \u00e7ok say\u0131daki mutasyon (mutasyon f\u0131rt\u0131nas\u0131) virusun \u00e7o\u011falamayacak ve b\u00fct\u00fcnl\u00fc\u011f\u00fcn\u00fc koruyamayacak kadar de\u011fi\u015fmesine neden olmaktad\u0131r. \u0130lac\u0131n konak h\u00fccre RNA\u2019s\u0131nda ise mutasyona yol a\u00e7mad\u0131\u011f\u0131 bildirilmi\u015ftir (1).<\/p>\n<p>Molnupiravirin SARS-CoV-2 ile infekte farelerde hem profilaktik, hem de terap\u00f6tik uygulanmas\u0131 etkili bulunmu\u015f, akci\u011fer fonksiyonlar\u0131n\u0131 iyile\u015ftirdi\u011fi, akci\u011ferdeki virus titrelerini d\u00fc\u015f\u00fcrd\u00fc\u011f\u00fc g\u00f6sterilmi\u015ftir. Bu \u00f6zellikleriyle gelecekte ortaya \u00e7\u0131kabilecek zoonotik koronaviruslar i\u00e7in de alternatif olabilece\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir (2). Gelincik modelinde, g\u00fcnde 2 kez uygulanan molnupiravir tedavisi \u00fcst solunum yollar\u0131ndaki SARS-CoV-2 viral y\u00fck\u00fcn\u00fc belirgin olarak azaltm\u0131\u015f ve tedavi almayan hayvanlara infeksiyon bula\u015fmas\u0131n\u0131 engellemi\u015ftir. Bu \u00e7al\u0131\u015fmada erken d\u00f6nemde ba\u015flanan molnupiravirin daha etkili olabildi\u011fi g\u00f6r\u00fclm\u00fc\u015ft\u00fcr (3).<\/p>\n<p>Faz 1 klinik \u00e7al\u0131\u015fmada molnupiravirin\u00a0 tek doz ve \u00e7ok say\u0131da doz uygulanmas\u0131n\u0131n sa\u011fl\u0131kl\u0131 g\u00f6n\u00fcll\u00fclerde iyi tolere edildi\u011fi ve dozla orant\u0131l\u0131 bir farmakokineti\u011fi oldu\u011fu g\u00f6sterilmi\u015f,\u00a0 Faz-2\u2019de\u00a0 ideal doz olarak 2X800mg\/g\u00fcn, 5 g\u00fcn s\u00fcreyle uygulanmas\u0131n\u0131n uygun oldu\u011fu sonucuna var\u0131lm\u0131\u015ft\u0131r (4).<\/p>\n<p>Molnupiravirin yatan (MOVeIN)\u00a0 ve ayaktan (MOVeOUT) hastalarda y\u00fcr\u00fct\u00fclen faz II\/III klinik \u00e7al\u0131\u015fmalar\u0131n\u0131n ara analizinde, yatan hastalarda herhangi olumlu bir etkisi g\u00f6r\u00fclmedi\u011fi MOVeIN \u00e7al\u0131\u015fmas\u0131 sonland\u0131r\u0131lm\u0131\u015f ve\u00a0 ayaktan hastalardaki\u00a0 MOVeOUT \u00e7al\u0131\u015fmas\u0131na devam edilmesi kararla\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r (5).<\/p>\n<p>Hindistan\u2019da hafif seyirli 741 COVID-19 olgusunda yap\u0131lm\u0131\u015f bir di\u011fer randomize kontroll\u00fc \u00e7al\u0131\u015fmada, tek ba\u015f\u0131na standard bak\u0131mla kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda, ek olarak\u00a0 800 mg X2\/g\u00fcn, 5 g\u00fcn molnupiravir verilen hastalarda\u00a0 5, 10 ve 14. g\u00fcnlerde daha y\u00fcksek oranda klinik iyile\u015fme (s\u0131ras\u0131yla %63 vs % 22; P<0.0001; %79\u00a0 vs\u00a0 %49.5; P<0.0001; %81.5 vs %73.2; P=0.015) g\u00f6r\u00fclm\u00fc\u015f ve klinik iyile\u015fme s\u00fcresi molnupiravir grubunda 8 g\u00fcnken kontrol grubunda 12 g\u00fcn (P=0.0001)\u00a0olarak belirlenmi\u015ftir. Bu \u00e7al\u0131\u015fmada 5., 10. ve 14.g\u00fcnde SARS CoV-2 RT-PCR negatifli\u011fi molnupiravir grubunda belirgin olarak daha y\u00fcksek olmu\u015f (P<0.0001), son olarak hastane ba\u015fvurusu da molnupiravir grubunda %1.89, kontrol grubunda ise %6.22 olarak belirlenmi\u015ftir\u00a0 (P=0.0027) (6). Yine Hindistan\u2019da yap\u0131lan bir ba\u015fka \u00e7al\u0131\u015fmada ise orta a\u011f\u0131rl\u0131ktaki COVID-19 hastalar\u0131nda etkisiz bulundu\u011fu a\u00e7\u0131klanm\u0131\u015ft\u0131r (7).\n\nA\u011f\u0131r COVID-19 a\u00e7\u0131s\u0131ndan risk grubunda olan, semptomlar\u0131n\u0131n ilk 5 g\u00fcn\u00fcnde olup ayaktan izlenen hastalarla devam edilen MOVe-OUT \u00e7al\u0131\u015fmas\u0131na toplam 1850 hasta al\u0131nmas\u0131 planlanmaktayd\u0131. Ancak 1 Ekim 2021\u2019de sonu\u00e7lar\u0131 a\u00e7\u0131klanan ara analizde, 29 g\u00fcn sonunda hastane yat\u0131\u015f gerektirecek a\u011f\u0131rla\u015fma ve \u00f6l\u00fcm oran\u0131n\u0131n molnupiravirle tedavi edilen grupta %7.3 (28\/385), plasebo grubunda ise %14.1 (53\/377), (%50\u2019lik azalma, P=0.0012)\u00a0 oldu\u011funun g\u00f6r\u00fclmesi \u00fczerine (8), ba\u011f\u0131ms\u0131z\u00a0 komite ve FDA\u00a0 \u00e7al\u0131\u015fman\u0131n erken sonland\u0131r\u0131lmas\u0131n\u0131 \u00f6nermi\u015ftir.\n\nKas\u0131m 2021 tarihinde MOVe-OUT \u00e7al\u0131\u015fmas\u0131na dahil edilmi\u015f toplam 1433 hastan\u0131n son analiz sonu\u00e7lar\u0131 duyurulmu\u015ftur. Buna g\u00f6re ayaktan, riskli hasta grubunda \u00f6l\u00fcm ve hastane yat\u0131\u015f\u0131 oran\u0131n\u0131n\u00a0 molnupiravir grubunda\u00a0 %6.8 (48\/709), plasebo grubunda %9.7 oldu\u011fu, %3\u2019l\u00fck mutlak risk azalmas\u0131 (%95CI: 0.1-5.9; nominal P=0.0218) g\u00f6zlendi\u011fi,\u00a0 relatif risk azalmas\u0131n\u0131nsa\u00a0 %30 (RR: 0.70; %95CI: 0.49-0.99) oldu\u011fu bildirilmi\u015ftir. Molnupiravir alan grupta \u00a01 hasta kaybedilirken, plasebo alan grupta 9 hastan\u0131n hayat\u0131n\u0131 kaybetti\u011fi; 3. ve 5.g\u00fcndeki viral klirens oranlar\u0131n\u0131n molnupiravir grubunda belirgin olarak daha y\u00fcksek oldu\u011fu ve istenmeyen ve ciddi istenmeyen etkilerin gruplar aras\u0131nda benzer oldu\u011fu duyurulmu\u015ftur (9, 10).\n\n11 Ekim 2021 tarihinde ilgili firma FDA\u2019ya molnupiravirin COVID-19 tedavisinde kullan\u0131m onay\u0131n\u0131 almak \u00fczere ba\u015fvurmu\u015f (11), \u00a04 Kas\u0131m 2021 tarihinde ise \u0130ngiltere, COVID-19 tedavisinde\u00a0 molnupiravire kullan\u0131m onay\u0131 veren ilk \u00fclke olmu\u015ftur (12).\n\n19 Kas\u0131m 2021 tarihinde ise EMA uzman dan\u0131\u015fman kurulu, hafif seyirli eri\u015fkin semptomatik \u00a0COVID-19 hastalar\u0131n\u0131n tedavisinde, a\u011f\u0131r hastal\u0131k a\u00e7\u0131s\u0131ndan riskli olmalar\u0131 durumunda molnupiravir kullan\u0131m\u0131n\u0131 tavsiye etmi\u015ftir (13).\n\n1 Aral\u0131k 2021 tarihinde de FDA uzman dan\u0131\u015fma kurulu, molnupiravirin yine hafif seyirli ve riskli semptomatik COVID-19 hastalar\u0131 i\u00e7in kullan\u0131lmas\u0131n\u0131 tavsiye etmi\u015ftir (14).\n\n\u00dcretici firma Hindistan\u2019da 8 firmaya, d\u00fc\u015f\u00fck ve orta d\u00fc\u015f\u00fck gelirli \u00fclkelerde kullan\u0131lmak \u00fczere jenerik molnupiravir \u00fcretimi i\u00e7in izin vermi\u015ftir. B\u00f6ylece\u00a0 yoksul \u00fclkeler i\u00e7in, ABD\u2019de $712 olan 5 g\u00fcnl\u00fck tedavi maliyetinin,\u00a0 $10\u2019a kadar d\u00fc\u015f\u00fcr\u00fclebilece\u011fi beklenmektedir (15) .\n\n\u00dclkemizden de merkezlerin dahil oldu\u011fu molnupiravirin temasl\u0131 ki\u015filerde profilaksi amac\u0131yla kullan\u0131m\u0131n\u0131n ara\u015ft\u0131r\u0131ld\u0131\u011f\u0131 Faz-III \u00e7al\u0131\u015fma ise Ekim 2021\u2019de ba\u015flam\u0131\u015f olup halen devam etmektedir.\n\nMolnupiravirin ara \u00fcr\u00fcnlerinin DNA sentezinde kullan\u0131labilece\u011fine dair Zhou ve ark. taraf\u0131ndan yap\u0131lan bir <em>in-vitro<\/em>\u00a0 \u00e7al\u0131\u015fman\u0131n yay\u0131mlanmas\u0131n\u0131n ard\u0131ndan, bu ajan\u0131n insan h\u00fccrelerinde de mutasyonu tetikleyebilece\u011fi y\u00f6n\u00fcnde ku\u015fkular ortaya \u00e7\u0131km\u0131\u015ft\u0131r (16). Ancak ilgili firma, genotoksisite analizlerinin detayl\u0131 bir \u015fekilde ve uygun y\u00f6ntemlerle yap\u0131ld\u0131\u011f\u0131n\u0131, preklinik <em>in-vivo<\/em> hayvan mutajenisite\u00a0 \u00e7al\u0131\u015fmalar\u0131nda (Pig-a mutagenicity assay and Big Blue [cII locus] transgenic rodent assay) sorun belirlenmedi\u011fini bildirmi\u015f,\u00a0 Zhou ve ark.\u2019n\u0131n\u00a0 \u00e7al\u0131\u015fmas\u0131nda kullan\u0131lan y\u00f6ntemlerin uygun olmad\u0131\u011f\u0131n\u0131 ifade ederek\u00a0 bulgulara itiraz etmi\u015ftir (17). \u00a0FDA dan\u0131\u015fma kurulu da firman\u0131n yapt\u0131\u011f\u0131 genotoksisite \u00e7al\u0131\u015fmalar\u0131n\u0131n yeterli oldu\u011funu bildirmi\u015ftir (10).<\/p>\n<p>Molnupiravirle ili\u015fkili bir di\u011fer kayg\u0131ysa, molnupiravir gibi mutajenik antivirallerin virusta mutasyonu uyarmas\u0131n\u0131n bir sonucu olarak yeni ve daha tehlikeli olabilecek varyantlar\u0131n ortaya \u00e7\u0131kmas\u0131na yol a\u00e7abilece\u011fi konusundaki hipotezlerdir. Bu hipotezi ileri s\u00fcrenler, olas\u0131 mutant bir virusun ba\u015fkalar\u0131na bula\u015fmamas\u0131 i\u00e7in molnupiravir kullanan ki\u015filerin izolasyonunun \u00f6nemine vurgu yapmaktad\u0131r (18). Ancak molnupiravirin virusta neden oldu\u011fu yo\u011fun mutasyon, virus i\u00e7in s\u0131kl\u0131kla k\u0131sa s\u00fcrede \u00f6l\u00fcmc\u00fcl oldu\u011fundan bu kayg\u0131n\u0131n klinik \u00f6nemi hen\u00fcz bilinmemektedir.<\/p>\n<p><strong><em>\u00d6neri <\/em><\/strong><\/p>\n<p><strong><em>COVID-19 \u00fclkemizde halen her g\u00fcn y\u00fczlerce \u00f6l\u00fcme yol a\u00e7maktad\u0131r. Hastal\u0131\u011f\u0131n erken tedavisinde kullan\u0131labilecek, daha etkili ba\u015fka bir oral antiviral\u00a0 bulunmamaktad\u0131r. Bu nedenle, ayaktan izlenen veya ba\u015fka nedenlerle hastanede yatarken COVID-19 tan\u0131s\u0131 konulup, semptomlar\u0131n\u0131n ilk 5 g\u00fcn\u00fcnde olan hafif-orta \u015fiddetli COVID-19 olgular\u0131nda,\u00a0 a\u011f\u0131r COVID-19 i\u00e7in en az 1 risk fakt\u00f6r\u00fc bulunmas\u0131 halinde\u00a0 molnupiravirin kullan\u0131lmas\u0131 uygun olacakt\u0131r. <\/em><\/strong><\/p>\n<p><strong><em>Molnupiravirin kullan\u0131m dozu ve s\u00fcresi; 2X800mg\/g\u00fcn, toplam 5 g\u00fcn \u015feklindedir. <\/em><\/strong><\/p>\n<p><strong>Kaynaklar<\/strong><\/p>\n<ol>\n<li><em>Pruijssers AJ, Denison MR. Nucleoside analogues for the treatment of coronavirus infections. Current Opinion in Virololgy 2019;35:57-62. doi: 10.1016\/j.coviro.2019.04.002. <\/em><\/li>\n<li><em>Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijssers AJ, et al. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Science Translational Medicine 2020;12(541):eabb5883. doi: 10.1126\/scitranslmed.abb5883<\/em><\/li>\n<li><em>Cox RM, Wolf JD, Plemper RK. Therapeutically administered ribonucleoside analogue MK-4482\/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nature Microbiology 2021 ;6(1):11-18. doi: 10.1038\/s41564-020-00835-2. <\/em><\/li>\n<li><em>Painter<\/em><em> WP, <\/em><em>Holman<\/em><em> W, Bush JA, Almazedi F, Malik H, et al. Human Safety, Tolerability, and Pharmacokinetics of a Novel Broad-Spectrum Oral Antiviral Compound, Molnupiravir, with Activity Against SARS-CoV-2. <\/em><em>medRxiv preprint 2020; doi: <\/em><a href=\"https:\/\/doi.org\/10.1101\/2020.12.10.20235747\"><em>https:\/\/doi.org\/10.1101\/2020.12.10.20235747<\/em><\/a> <em>[accessed 16 June 2021].<\/em><\/li>\n<li><a href=\"https:\/\/www.businesswire.com\/news\/home\/20210415005258\/en\/\"><em>https:\/\/www.businesswire.com\/news\/home\/20210415005258\/en\/<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.heteroworld.com\/images\/Press_Release_Molnupiravir_Interim_Clinical_Results_Final_090721.pdf\"><em>https:\/\/www.heteroworld.com\/images\/Press_Release_Molnupiravir_Interim_Clinical_Results_Final_090721.pdf<\/em><\/a><\/li>\n<li><em>Willyard C. Nature 2021; \u00a0<\/em><a href=\"https:\/\/doi.org\/10.1038\/d41586-021-02783-1\"><em>https:\/\/doi.org\/10.1038\/d41586-021-02783-1<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.merck.com\/news\/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat\/\"><em>https:\/\/www.merck.com\/news\/merck-and-ridgebacks-investigational-oral-antiviral-molnupiravir-reduced-the-risk-of-hospitalization-or-death-by-approximately-50-percent-compared-to-placebo-for-patients-with-mild-or-moderat\/<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.merck.com\/news\/merck-and-ridgeback-biotherapeutics-provide-update-on-results-from-move-out-study-of-molnupiravir-an-investigational-oral-antiviral-medicine-in-at-risk-adults-with-mild-to-moderate-covid-19\">https:\/\/www.merck.com\/news\/merck-and-ridgeback-biotherapeutics-provide-update-on-results-from-move-out-study-of-molnupiravir-an-investigational-oral-antiviral-medicine-in-at-risk-adults-with-mild-to-moderate-covid-19<\/a><\/li>\n<li><a href=\"https:\/\/www.fda.gov\/media\/154419\/download\"><em>https:\/\/www.fda.gov\/media\/154419\/download<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.merck.com\/news\/merck-and-ridgeback-announce-submission-of-emergency-use-authorization-application-to-the-u-s-fda-for-molnupiravir-an-investigational-oral-antiviral-medicine-for-the-treatment-of-mild-to-moderate-c\/\"><em>https:\/\/www.merck.com\/news\/merck-and-ridgeback-announce-submission-of-emergency-use-authorization-application-to-the-u-s-fda-for-molnupiravir-an-investigational-oral-antiviral-medicine-for-the-treatment-of-mild-to-moderate-c\/<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.gov.uk\/government\/news\/first-oral-antiviral-for-covid-19-lagevrio-molnupiravir-approved-by-mhra#:~:text=and%20licensing%20guidance-,First%20oral%20antiviral%20for%20COVID%2D19%2C%20Lagevrio%20(molnupiravir),review%20of%20the%20available%20evidence\"><em>https:\/\/www.gov.uk\/government\/news\/first-oral-antiviral-for-covid-19-lagevrio-molnupiravir-approved-by-mhra#:~:text=and%20licensing%20guidance-,First%20oral%20antiviral%20for%20COVID%2D19%2C%20Lagevrio%20(molnupiravir),review%20of%20the%20available%20evidence<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.ema.europa.eu\/en\/news\/ema-issues-advice-use-lagevrio-molnupiravir-treatment-covid-19\"><em>https:\/\/www.ema.europa.eu\/en\/news\/ema-issues-advice-use-lagevrio-molnupiravir-treatment-covid-19<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.cnbc.com\/2021\/11\/30\/fda-advisory-panel-narrowly-endorses-mercks-oral-covid-treatment-pill-despite-reduced-efficacy.html\"><em>https:\/\/www.cnbc.com\/2021\/11\/30\/fda-advisory-panel-narrowly-endorses-mercks-oral-covid-treatment-pill-despite-reduced-efficacy.html<\/em><\/a><\/li>\n<li><a href=\"https:\/\/www.nytimes.com\/2021\/10\/17\/health\/covid-treatment-access-molnupiravir.html\"><em>https:\/\/www.nytimes.com\/2021\/10\/17\/health\/covid-treatment-access-molnupiravir.html<\/em><\/a><em>. <\/em><\/li>\n<li><em>Zhou S. The Journal of Infectious Diseases\u00ae 2021;224:415\u20139.<\/em><\/li>\n<li><em>Troth S. The Journal of Infectious Diseases, jiab362,\u00a0<\/em><a href=\"https:\/\/doi.org\/10.1093\/infdis\/jiab362\"><em>https:\/\/doi.org\/10.1093\/infdis\/jiab362<\/em><\/a><\/li>\n<li><em>https:\/\/virological.org\/t\/mutagenic-antivirals-the-evolutionary-risk-of-low-doses\/768<\/em><\/li>\n<li>Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients. N Engl J Med. 2021 Dec 16. doi: 10.1056\/NEJMoa2116044. Epub ahead of print. PMID: 34914868.<\/li>\n<\/ol>\n            <\/div>\n    \n            <div post_id=\"5310\" itemcount=\"6\"  header_id=\"header-1600777520530\" id=\"header-1600777520530\" style=\"\" class=\"accordions-head head1600777520530 border-none\" toggle-text=\"\" main-text=\"PAKSLOV\u0130D (PF-07321332+ritonavir)\">\n                                    <span id=\"accordion-icons-1600777520530\" class=\"accordion-icons\">\n                        <span class=\"accordion-icon-active accordion-plus\"><i class=\"fas fa-chevron-up\"><\/i><\/span>\n                        <span class=\"accordion-icon-inactive accordion-minus\"><i class=\"fas fa-chevron-right\"><\/i><\/span>\n                    <\/span>\n                    <span id=\"header-text-1600777520530\" class=\"accordions-head-title\">PAKSLOV\u0130D (PF-07321332+ritonavir)<\/span>\n                            <\/div>\n            <div class=\"accordion-content content1600777520530 \">\n                <p>PF-00835321 ve onun yeni tasarlanm\u0131\u015f fosfat \u00f6n ilac\u0131 olan PF-07304814, koronaviruslar\u0131n ana proteaz\u0131na (Mpro) kar\u015f\u0131, insan proteazlar\u0131ndan daha fazla olmak \u00fczere <em>in-vitro<\/em> potent inhibit\u00f6r etki g\u00f6stermektedir. \u0130lk kez 2003 y\u0131l\u0131nda SARS i\u00e7in geli\u015ftirilmi\u015f olan bu ila\u00e7la ilgili \u00e7al\u0131\u015fmalar, SARS salg\u0131n\u0131n\u0131n sonlanmas\u0131yla klinik kullan\u0131ma uygun hale getirilemeden sonland\u0131r\u0131lm\u0131\u015ft\u0131r. COVID-19\u2019un ortaya \u00e7\u0131kmas\u0131, ve SARS-CoV-2 Mpro proteinin SARS ile neredeyse ayn\u0131 oldu\u011funun anla\u015f\u0131lmas\u0131 \u00fczerine, bu ajan\u0131n COVID-19\u2019da kullan\u0131labilece\u011fi d\u00fc\u015f\u00fcn\u00fclerek \u00e7al\u0131\u015fmalar ba\u015flat\u0131lm\u0131\u015ft\u0131r. Klinik \u00f6ncesi \u00e7al\u0131\u015fmalarda PF-00835231\u2019in SARS-CoV-2\u2019ye kar\u015f\u0131 da <em>in vitro<\/em> potent antiviral etkinli\u011fi ve farmas\u00f6tik \u00f6zelliklerinin uygun oldu\u011fu g\u00f6r\u00fclm\u00fc\u015ft\u00fcr.<\/p>\n<p>\u0130V olarak uygulanabilen PF07304814\u2019\u00fcn oral formu PF07321332 ad\u0131yla geli\u015ftirilmi\u015ftir. PF-07321332\u2019nin oral biyoyararlan\u0131m\u0131n\u0131n iyi olmas\u0131, COVID-19\u2019un klinik y\u00f6netimi i\u00e7in olduk\u00e7a avantajl\u0131d\u0131r (1, 2, 3).\u00a0 PF-07304814 (IV) ve PF-07321332 (oral)\u2019nin klinik \u00e7al\u0131\u015fmalar\u0131n\u0131n bir k\u0131sm\u0131 tamamlanm\u0131\u015f, bir k\u0131sm\u0131 ise devam etmektedir. Oral form olan PF-07321332 klinik \u00e7al\u0131\u015fmalarda ritonavirle birlikte kullan\u0131lm\u0131\u015f olup, bu kombinasyona pakslovid ad\u0131 verilmi\u015ftir.\u00a0 Faz-2-3 \u00e7al\u0131\u015fmas\u0131n\u0131n bas\u0131nla payla\u015f\u0131lan ara analiz sonu\u00e7lar\u0131nda, a\u011f\u0131r hastal\u0131k a\u00e7\u0131s\u0131ndan riskli, semptomlar\u0131n\u0131n ilk 3-5 g\u00fcn\u00fcnde olan 1219 eri\u015fkin COVID-19 hastas\u0131nda, pakslovidin hastane yat\u0131\u015f\u0131 ve \u00f6l\u00fcm riskini 89% azaltt\u0131\u011f\u0131 bildirilmi\u015ftir (4, 5). Bu verilerle ilac\u0131n yarar\u0131 g\u00f6sterildi\u011fi i\u00e7in,\u00a0 ba\u011f\u0131ms\u0131z de\u011ferlendirme komisyonu ve FDA \u00e7al\u0131\u015fman\u0131n sonland\u0131r\u0131lmas\u0131n\u0131 \u00f6nermi\u015f ve ilgili firma FDA\u2019ya acil kullan\u0131m onay\u0131 i\u00e7in ba\u015fvurarak, 22\/12\/2021 tarihinde bu onay\u0131 alm\u0131\u015ft\u0131r. Molnupiravirde oldu\u011fu gibi pakslovid i\u00e7inde ilgili firma, d\u00fc\u015f\u00fck ve orta d\u00fc\u015f\u00fck gelirli \u00fclkelerde patent hakk\u0131ndan vazge\u00e7ti\u011fini duyurmu\u015ftur.<\/p>\n<p><strong><em>\u00d6neri<\/em><\/strong><\/p>\n<p><em><strong>Pakslovid, Faz-3 \u00e7al\u0131\u015fmas\u0131nda COVID-19\u2019a kar\u015f\u0131 y\u00fcksek etkinlik g\u00f6stermi\u015f ve COVID-19\u2019da kullan\u0131lmak \u00fczere FDA\u2019dan acil kullan\u0131m onay\u0131 alm\u0131\u015ft\u0131r. Bu nedenle, ayaktan izlenen veya ba\u015fka nedenlerle hastanede yatarken COVID-19 tan\u0131s\u0131 konulup, semptomlar\u0131n\u0131n ilk 5 g\u00fcn\u00fcnde olan hafif-orta \u015fiddetli COVID-19 olgular\u0131nda, a\u011f\u0131r COVID-19 i\u00e7in en az 1 risk fakt\u00f6r\u00fc bulunmas\u0131 halinde pakslovidin kullan\u0131lmas\u0131 uygun olacakt\u0131r.<\/strong><\/em><\/p>\n<p><strong>Kaynaklar<\/strong><\/p>\n<ol>\n<li><em>Hoffman RL, Kania RS, Brothers MA, Davies JF, Ferre RA et al. Discovery of ketone-based covalent inhibitors of coronavirus 3CL proteases for the potential therapeutic treatment of COVID-19J. Journal of Medical Chemistry 2020; 63(21): 12725\u201312747 \u00a0doi:\u00a010.1021\/acs.jmedchem.0c01063<\/em><\/li>\n<li><em>Boras B, Jones RM, Anson BJ, Arenson D, Aschenbrenner L, et al. Discovery of a novel inhibitor of coronavirus 3CL protease as a clinical candidate for the potential treatment of COVID-19. bioRxiv [Preprint]. 2020:2020.09.12.293498. doi: 10.1101\/2020.09.12.293498; [accessed 16 June 2021].<\/em><\/li>\n<li><em>Dolgin E. The race for antiviral drugs to beat COVID - and the next pandemic. Nature 2021;592(7854):340-343. doi: 10.1038\/ d41586-021-00958-4<\/em><\/li>\n<li><em>Mahase E. Covid-19: Pfizer\u2019s paxlovid is 89% effective in patients at risk of serious illness, company reports . BMJ2021;\u00a0375<\/em><em>:n2713<\/em><em>. <\/em><em>doi:\u00a0<\/em><a href=\"https:\/\/doi.org\/10.1136\/bmj.n2713\"><em>https:\/\/doi.org\/10.1136\/bmj.n2713<\/em><\/a><em>\u00a0<\/em><\/li>\n<li><a href=\"https:\/\/www.pfizer.com\/news\/press-release\/press-release-detail\/pfizer-provide-us-government-10-million-treatment-courses\"><em>https:\/\/www.pfizer.com\/news\/press-release\/press-release-detail\/pfizer-provide-us-government-10-million-treatment-courses<\/em><\/a><\/li>\n<li>Coronavirus (COVID-19) Update: FDA Authorizes First Oral Antiviral for Treatment of COVID-19. <a href=\"https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19n\">https:\/\/www.fda.gov\/news-events\/press-announcements\/coronavirus-covid-19-update-fda-authorizes-first-oral-antiviral-treatment-covid-19n<\/a><\/li>\n<\/ol>\n            <\/div>\n    <\/div>\n\n\n\n            <\/div><\/p>\n","protected":false},"excerpt":{"rendered":"<p>COVID-19 patogenezinde erken d\u00f6nemde virusun, sonras\u0131ndaysa konak savunmas\u0131n\u0131n rol ald\u0131\u011f\u0131 bilinmektedir. Bu nedenle (&#8230;)<\/p>\n","protected":false},"author":1,"featured_media":5315,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[5],"tags":[],"_links":{"self":[{"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/posts\/5309"}],"collection":[{"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/comments?post=5309"}],"version-history":[{"count":8,"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/posts\/5309\/revisions"}],"predecessor-version":[{"id":5417,"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/posts\/5309\/revisions\/5417"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/media\/5315"}],"wp:attachment":[{"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/media?parent=5309"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/categories?post=5309"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.klimik.org.tr\/koronavirus\/wp-json\/wp\/v2\/tags?post=5309"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}