Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
COVID-19 Tedavisinde Kullanılan İlaçların Yan Etki Sıklığının Değerlendirilmesi: Bir Retrospektif Araştırma
Evaluation of the Frequency of Side Effects of Drugs Used in the Treatment of COVID-19: A Retrospective Study
Esma ERYILMAZ ERENa, İlhami ÇELİKa, Didem ERENa, Emine ARMAN FIRATa, Ulaş Serkan TOPALOĞLUb, Mehmet KARAc, Berna BOZBAYa, Ayşegül ULU KILIÇd
aKayseri Şehir Hastanesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Kliniği, Kayseri, TÜRKİYE
bKayseri Şehir Hastanesi, İç Hastalıkları Kliniği, Kayseri, TÜRKİYE
cKayseri Şehir Hastanesi, Tıbbi Farmakoloji Kliniği, Kayseri, TÜRKİYE
dErciyes Üniversitesi Tıp Fakültesi, Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji ABD, Kayseri, TÜRKİYE
Turkiye Klinikleri J Med Sci. 2021;41(4):410-5
doi: 10.5336/medsci.2020-78763
Article Language: TR
Full Text
ÖZET
 Amaç: Koronavirüs hastalığı-2019 [coronavirus disease-2019 (COVID-19)] tedavisinde kullanılan antiviral, antibakteriyel ve immünomodülatör etkili ilaçların, kombinasyon şeklinde veya monoterapi olarak kullanımında görülen yan etkilerinin sıklığını belirlenmesi amaçlanmıştır. Gereç ve Yöntemler: Bu retrospektif çalışmada, COVID-19 tanısı ile hidroksiklorokin, makrolid ve favipiravir tedavilerini monoterapi veya kombinasyon şeklinde almış olan hastalar, yan etki gelişimi açısından değerlendirildi. Hastaların demografik ve klinik verileri, aldıkları diğer tedaviler ve gelişen yan etkiler kaydedildi. Bulgular: Çalışma süresi boyunca, 337 hastanın verileri incelendi. Hastaların medyan yaşı 56 (19-94) idi ve 184'ü (%54,6) erkekti. Hipertansiyon en sık (%29,9) eşlik eden komorbidite idi. Pnömoni saptanan 272 (%80,7) hastanın 210'unda (%62,3) yaygın infiltrasyon saptandı. Hastaların 18'i (%5,3) yalnız hidroksiklorokin, 86'sı (%25,5) yalnız makrolid, 193'ü (%57,3) hidroksiklorokin ve makrolid, 40'ı (%11,9) ise hidroksiklorokin, makrolid ve favipiravir 3'lü kombinasyonunu almıştı. Hidroksiklorokin monoterapisi alan 2 (%11,1) hastada, makrolid monoterapisi alan 4 (%4,7) hastada, hidroksiklorokin-makrolid kombinasyonu alan 55 (%28,5) hastada ve hidroksiklorokin-makrolid-favipiravir kombinasyonu alan 4 (%10,0) hastada yan etki kaydı mevcut idi. Hidroksiklorokin ve makrolid kombinasyonu alan grupta en sık (%12,9) görülen yan etkinin QT uzaması olduğu gözlemlendi. En sık (%7,3) görülen gastrointestinal sistem yan etkisinin ise bulantı olduğu saptandı. Sonuç: COVID-19 tedavisi için kullanılan antiviral, antibakteriyel ve immünomodülatör ilaçların kombinasyon şeklinde kullanılması hâlinde yan etki gelişiminin sıklığı artmaktadır.

Anahtar Kelimeler: COVID-19; hidroksiklorokin; makrolidler; favipiravir; istenmeyen etkiler
ABSTRACT
 Objective: It is aimed to determine the frequency of side effects seen in the use of antiviral, antibacterial and immunomodulatory drugs used in the treatment of coronavirus disease-2019 (COVID-19) in combination or monotherapy. Material and Methods: In this retrospective study, patients with a diagnosis of COVID-19 who received hydroxychloroquine, macrolide, and favipiravir treatments in combination or monotherapy were evaluated in terms of the development of side effects. Demographic and clinical data of the patients, other treatments they received and the side effects that occurred were recorded. Results: During the study period, data from 337 patients were analyzed. The median age of the patients was 56 (19-94), and 184 (54.6%) were male. Hypertension was the most common comorbidity (29.9%). Diffuse infiltration was detected in 210 (62.3%) of 272 (80.7%) patients with pneumonia. Eighteen (5.3%) patients received only hydroxychloroquine, 86 (25.5%) had only macrolide, 193 (57.3%) had hydroxychloroquine and macrolide, and 40 (11.9%) had hydroxychloroquine, macrolide and favipiravir triple combination. Side effects were observed in 2 (11.1%) patients receiving hydroxychloroquine monotherapy, 4 (4.7%) patients receiving macrolide monotherapy, 55 (28.5%) patients receiving hydroxychloroquine-macrolide combination, and 4 (10.0%) patients receiving hydroxychloroquine-macrolidefavipiravir combination. It was observed that the most common (12.9%) side effect in the group receiving the combination of hydroxychloroquine and macrolide was QT prolongation. The most common (7.3%) side effect of the gastrointestinal system was found to be nausea. Conclusion: The frequency of side effects increases when antiviral, antibacterial and immunomodulatory drugs used for the treatment of COVID-19 are used in combination.

Keywords: COVID-19; hydroxychloroquine; macrolides; favipiravir; adverse effect
REFERENCES:
  1. Cucinotta D, Vanelli M. WHO Declares COVID-19 a Pandemic. Acta Biomed. 2020; 91(1):157-60. [PubMed] [PMC] 
  2. World Health Organisation [İnternet]. [Erişim tarihi: 29 Ağustos 2020]. Health Emergency Dashboard: WHO Coronavirus disease (COVID-19) Situation reports. [Link] 
  3. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-ınfected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. Erratum in: JAMA. 2021;325(11):1113. [Crossref] [PubMed] [PMC] 
  4. Wolff D, Nee S, Hickey NS, Marschollek M. Risk factors for Covid-19 severity and fatality: a structured literature review. Infection. 2021;49(1):15-28. [Crossref] [PubMed] [PMC] 
  5. Esposito S, Noviello S, Pagliano P. Update on treatment of COVID-19: ongoing studies between promising and disappointing results. Infez Med. 2020;28(2):198-211. [PubMed] 
  6. Sethi A, Bach H. Evaluation of current therapies for COVID-19 treatment. Microorganisms. 2020;8(8):1097. [Crossref] [PubMed] [PMC] 
  7. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. In vitro antiviral activity and projection of optimized dosing design of hydroxychloroquine for the treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020; 71(15):732-9. [Crossref] [PubMed] [PMC] 
  8. Zhou D, Dai SM, Tong Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J Antimicrob Chemother. 2020; 75(7):1667-70. [Crossref] [PubMed] [PMC] 
  9. Andreani J, Le Bideau M, Duflot I, Jardot P, Rolland C, Boxberger M, et al. In vitro testing of combined hydroxychloroquine and azith romycin on SARS-CoV-2 shows synergistic effect. Microb Pathog. 2020;145:104228. [Crossref] [PubMed] [PMC] 
  10. Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;56(1):105949. [Crossref] [PubMed] [PMC] 
  11. Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J, et al. Experimental treatment with favipiravir for COVID-19: An open-label control study. Engineering (Beijing). 2020;6(10):1192-8. [Crossref] [PubMed] [PMC] 
  12. Song J, Hu W, Yu Y, Shen X, Wang Y, Yan J, et al. A comparison of clinical characteristics and outcomes in elderly and younger patients with COVID-19. Med Sci Monit. 2020; 26:e925047. [Crossref] [PubMed] [PMC] 
  13. İnkaya AÇ, Taş Z, Akova M. COVID-19'un güncel tedavisi. Yalçın Ş, Özet A, editörler. Kanser ve COVID-19 Pandemisi. 1. Baskı. Ankara: Türkiye Klinikleri; 2020. p.27-37. [Link] 
  14. Naksuk N, Lazar S, Peeraphatdit TB. Cardiac safety of off-label COVID-19 drug therapy: a review and proposed monitoring protocol. Eur Heart J Acute Cardiovasc Care. 2020; 9(3):215-21. [Crossref] [PubMed] [PMC] 
  15. Poluzzi E, Raschi E, Motola D, Moretti U, De Ponti F. Antimicrobials and the risk of torsades de pointes: the contribution from data mining of the US FDA adverse event reporting system. Drug Saf. 2010;33(4):303-14. [Crossref]  [PubMed] 
  16. Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB. Pharmacologic treatments for Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;323(18):1824-36. [Crossref] [PubMed] 
  17. Wang L, He W, Yu X, Hu D, Bao M, Liu H, et al. Coronavirus disease 2019 in elderly patients: Characteristics and prognostic factors based on 4-week follow-up. J Infect. 2020; 80(6):639-45. [Crossref] [PubMed] [PMC] 

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