hujpharm Hacettepe University Journal of the Faculty of Pharmacy 2458-8806 Hacettepe University 10.52794/hujpharm.903721 Pharmacology and Pharmaceutical Sciences Eczacılık ve İlaç Bilimleri Pharmacovigilance Activities in the Treatment of COVID-19 COVID-19 Tedavisinde Farmakovijilans Aktiviteleri https://orcid.org/0000-0003-1928-566X Özal Gizem EXCELYA https://orcid.org/0000-0003-1172-1711 İnceoğlu Bilge EXCELYA https://orcid.org/0000-0001-5865-8110 Süzgeç Sezen EXCELYA https://orcid.org/0000-0001-7160-4408 Duran Nur Hilal EXCELYA https://orcid.org/0000-0003-0580-5337 Topaloğlu Gizem EXCELYA https://orcid.org/0000-0002-6767-9092 Arda Burcu EXCELYA https://orcid.org/0000-0001-7460-0576 Gulhan Ali EXCELYA 06 01 2021 41 2 93 101 03 26 2021 07 05 2021 Copyright © 1981, Hacettepe University Journal of the Faculty of Pharmacy 1981 Hacettepe University Journal of the Faculty of Pharmacy

The unexpected pandemic initiated by the new coronavirus 2019 (2019-nCoV) caused severe panic among people around the world since December 2019. Coronavirus disease 2019 (COVID-19) has wreaked havoc, and Health Authorities have started to make announcements and studies have been started quickly, for effective treatment and vaccination. In studies, drugs that reduce the symptoms of COVID-19 and alleviate the course of the disease have been used. In addition to the effects of these promising drugs, adverse events and multiple drug interactions have begun to appear all over the world, as well as in our country. Therefore, pharmacovigilance is of particular importance during the COVID-19 pandemic. Health authorities have been taking additional actions and measures in order to carry out adverse effects monitoring and risk minimization activities of drugs. In our study, we have reviewed the measures taken related to COVID-19 in Turkey and around the world along with safety of drugs used to treat COVID-19 and pharmacovigilance activities during the pandemic.

Aralık 2019’dan bu yana yeni tip koronavirüsün (2019-nCoV) başlattığı beklenmedik pandemi, dünyanın dört bir yanındaki insanlar arasında şiddetli paniğe neden olmuştur. Koronavirüs hastalığı 2019 (COVID-19) ciddi hasarlara yol açmış ve Sağlık otoriteleri tarafından yayınlanan duyurular ile etkili tedavi ve aşı için çalışmalara hızlıca başlanmıştır. Çalışmalarda, COVID-19 semptomlarını azaltıcı ve hastalığın seyrini hafifletici ilaçlar kulanılmaya başlanmıştır. Umut vadeden bu ilaçların etkilerinin yanısıra, tüm dünyada ve ülkemizde advers olaylar ve çoklu ilaç etkileşimleri görülmeye başlanmıştır. Bu nedenle, COVID-19 pandemi sürecinde farmakovijilans ayrı bir önem arz etmektedir. İlaçların advers etkilerinin takibi ve risk minimizasyon faaliyetlerini yürütmek açısından sağlık otoriteleri ek aksiyonlar ve önlemler almaktadır. Çalışmamızın amacı, Türkiye'de ve dünyada COVID-19 ile ilgili alınan önlemler ile birlikte, COVID-19 tedavisinde kullanılan ilaçların güvenliliği ve pandemi sürecindeki farmakovijilans aktivitelerini derlemektir.

 SARS-CoV-2 COVID-19 Pharmacovigilance Drug Safety Adverse Event SARS-CoV-2 COVID-19 Farmakovijilans İlaç Güvenliliği Advers Olay N/A N/A [1] “Genel Bilgiler, Epidemiyoloji ve Tanı,” 2020. [Online]. Available: https://covid19.saglik.gov.tr/TR-66337/genel-bilgiler-epidemiyoloji-ve-tani.html#. [2] A. L. YAĞCI İ., Sarikaya S., Ayhan F. F. , Bahsi A., Kaya B. B. , ERHAN B. , Ahi E. D. , Okan S., Ozkan Y., Korkmaz M. D. , Yaksi E., Kabayel D. D. , Ozdemir H., Kayalar G., Celik C., Kesiktas F. N. , Yagci H. C., “The effects of COVID-19 on Physical Medicine and Rehabilitation in Turkey in the first month of pandemic,” TURKISH J. Phys. Med. Rehabil., vol. 66, pp. 244–251, [Online]. Available: http://www.ftrdergisi.com/uploads/pdf/pdf_4214.pdf. [3] D.-G. Ahn et al., “Current Status of Epidemiology, Diagnosis, Therapeutics, and Vaccines for Novel Coronavirus Disease 2019 (COVID-19),” J. Microbiol. Biotechnol., vol. 30, pp. 313–324, 2020, doi: 10.4014/jmb.2003.03011. [4] M. Koska and H. Süslü, “Cutaneous Findings of COVID-19: A Review of the Literature,” J. Turkish Acad. Dermatology, vol. 14, pp. 30–43, Jun. 2020, doi: 10.4274/jtad.galenos.2020.36855. [5] P. Yamoah, T. M. Alalbila, V. Bangalee, and F. Oosthuizen, “Coronavirus Disease 2019 (COVID-19) Spread and Pharmacovigilance Implications: Expert Opinion,” Drug Inf. J., pp. 1–4, May 2020, doi: 10.1007/s43441-020-00158-8. [6] M. Uddin et al., “SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology, Vaccines, and Therapeutic Interventions,” Viruses, vol. 12, no. 5, p. 526, May 2020, doi: 10.3390/v12050526. [7] Z. Y. Zu et al., “Coronavirus Disease 2019 (COVID-19): A Perspective from China,” Radiology, vol. 296, no. 2, pp. E15–E25, Feb. 2020, doi: 10.1148/radiol.2020200490. [8] H. A. Rothan and S. N. Byrareddy, “The epidemiology and pathogenesis of coronavirus disease (COVID-19) outbreak,” J. Autoimmun., vol. 109, p. 102433, 2020, doi: https://doi.org/10.1016/j.jaut.2020.102433. [9] “Coronavirus Resource Center.” [Online]. Available: https://coronavirus.jhu.edu/. [10] “Coronavirus Resource Center: Turkey.” [Online]. Available: https://coronavirus.jhu.edu/region/turkey. [11] “‘Solidarity’ clinical trial for COVID-19 treatments.” [Online]. Available: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments. [12] “COVID-19: latest updates.” [Online]. Available: https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/covid-19-whats-new. [13] “Coronavirus Disease 2019 (COVID-19).” [Online]. Available: https://www.fda.gov/emergency-preparedness-and-response/counterterrorism-and-emerging-threats/coronavirus-disease-2019-covid-19. [14] “COVID-19 - Informations réglementaires.” [Online]. Available: https://www.ansm.sante.fr/Dossiers/COVID-19/COVID-19-Informations-reglementaires/(offset)/7. [15] “Pharmacovigilance et addictovigilance dans le contexte du COVID-19 : une surveillance renforcée.” [Online]. Available: https://www.ansm.sante.fr/Declarer-un-effet-indesirable/Systemes-de-vigilances-de-l-Agence/COVID-19-Dispositif-renforce-de-Pharmacovigilance-et-d-Addictovigilance/(offset)/0. [16] “DHSC and PHE statement on coronavirus,” 2020. [Online]. Available: https://www.gov.uk/government/news/dhsc-and-phe-statement-on-coronavirus. [17] “MHRA regulatory flexibilities resulting from coronavirus (COVID-19),” 2020. [Online]. Available: https://www.gov.uk/guidance/mhra-regulatory-flexibilities-resulting-from-coronavirus-covid-19#pharmacovigilance. [18] “COVID-19 Terms and MedDRA.” [Online]. Available: https://www.meddra.org/COVID-19-terms-and-MedDRA. [19] M. Iyer et al., “COVID-19: an update on diagnostic and therapeutic approaches,” BMB Rep., vol. 53, no. 4, pp. 191–205, Apr. 2020, doi: 10.5483/BMBRep.2020.53.4.080. [20] “The Drug Development Process.” [Online]. Available: https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process. [21] “Coronavirus (COVID-19) Update: FDA Continues to Facilitate Development of Treatments,” 2020. [Online]. Available: https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-continues-facilitate-development-treatments. [22] “Call to pool research resources into large multi-centre, multi-arm clinical trials to generate sound evidence on COVID-19 treatments,” 2020. [Online]. Available: https://www.ema.europa.eu/en/news/call-pool-research-resources-large-multi-centre-multi-arm-clinical-trials-generate-sound-evidence. [23] V. H.-L. Regás, M. T. D. Culla, and R. L. Bellfill, “Adverse reactions of drugs specifically used for treatment of SARS-CoV-2 infection,” Med. Clínica (English Ed., 2020. [24] “EU Risk Management Plan for Remdesivir.” [Online]. Available: https://www.ema.europa.eu/en/documents/rmp/veklury-epar-risk-management-plan_en.pdf. [25] T. P. Sheahan et al., “Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses,” Sci. Transl. Med., vol. 9, no. 396, 2017. [26] “Veklury (remdesivir): An overview of Veklury and why it is authorised in the EU,” 2020. [Online]. Available: https://www.ema.europa.eu/en/documents/overview/veklury-epar-medicine-overview_en.pdf. [27] S. Z. Tatlı, G. Çakar, B. Çolak, and E. T. Ö. Kızıl, “COVID-19 pandemisinde psikofarmakolojik tedavi,” Klin. Psikiyatr. Derg., p. 23, 2020. [28] S. A. Doggrell, “Remdesivir, a remedy or a ripple in severe COVID-19?,” Expert Opin. Investig. Drugs, vol. 29, no. 11, pp. 1195–1198, Nov. 2020, doi: 10.1080/13543784.2020.1821645. [29] B. Gasser and R. A. R. Uscategui, “POTENTIAL THERAPIES FOR TREATMENT OF COVID-19,” Rev. Ciência Veterinária e Saúde Pública, vol. 7, no. 1 SE-Artigos Originais, Aug. 2020, doi: 10.4025/revcivet.v7i1.55502. [30] “Summary on compassionate use: Remdesivir,” 2020. [Online]. Available: https://www.ema.europa.eu/en/documents/other/summary-compassionate-use-remdesivir-gilead_en.pdf. [31] T. Carr, “Doctors on the Front Lines Are Testing New Therapies to Treat COVID-19,” 2020. [Online]. Available: https://www.consumerreports.org/medical-treatments-procedures/new-therapies-to-treat-covid-19/. [32] “Clinical Management of COVID-19,” 2020. [Online]. Available: https://www.who.int/publications/i/item/clinical-management-of-covid-19. [33] G. Aksel, M. M. Islam, T. Aslan, and S. E. Eroglu, “Prolongation of QT interval due to hydroxychloroquine overdose used in COVID-19 treatment,” Turkish J. Emerg. Med., vol. 20, no. 3, pp. 149–151, Jul. 2020, doi: 10.4103/2452-2473.290063. [34] E. Mahase, “Coronavirus: covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate,” BMJ, vol. 368, 2020, doi: 10.1136/bmj.m641. [35] “Lopinavir and Ritonavir: MedlinePlus Drug Information.” [Online]. Available: https://medlineplus.gov/druginfo/meds/a602015.html. [36] N. Mehta, M. Mazer-Amirshahi, N. Alkindi, and A. Pourmand, “Pharmacotherapy in COVID-19; A narrative review for emergency providers,” Am. J. Emerg. Med., vol. 38, no. 7, pp. 1488–1493, Jul. 2020, doi: 10.1016/j.ajem.2020.04.035. [37] “A randomized, controlled open-label trial to evaluate the efficacy and safety of lopinavir-ritonavir in hospitalized patients with novel coronavirus pneumonia (COVID-19).” [Online]. Available: http://www.chictr.org.cn/showprojen.aspx?proj=48684. [38] A. Gérard et al., “‘Off-label’ use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: A survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers,” Therapies, vol. 75, no. 4, pp. 371–379, 2020, doi: https://doi.org/10.1016/j.therap.2020.05.002. [39] J. Sun et al., “Incidence of Adverse Drug Reactions in COVID-19 Patients in China: An Active Monitoring Study by Hospital Pharmacovigilance System,” Clin. Pharmacol. Ther., vol. 108, no. 4, pp. 791–797, Oct. 2020, doi: 10.1002/cpt.1866. [40] K. Pennington and E. Carmona, “Currently Available and Emerging Therapies for COVID-19.” [Online]. Available: https://www.chestnet.org/Guidelines-and-Resources/COVID-19/Currently-Available-and-Emerging-Therapies-for-COVID-19. [41] “What’s New in the Guidelines.” [Online]. Available: https://www.covid19treatmentguidelines.nih.gov/whats-new/. [42] P. Gautret et al., “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial,” Int. J. Antimicrob. Agents, vol. 56, no. 1, p. 105949, 2020, doi: https://doi.org/10.1016/j.ijantimicag.2020.105949. [43] I. Nessaibia, D. Siciliano, and A. Tahraoui, “Why nobody discusses the adverse psychiatric effects of chloroquine in case it might become the future treatment against COVID-19?,” Int. J. Health Plann. Manage., vol. n/a, no. n/a, Sep. 2020, doi: https://doi.org/10.1002/hpm.3057. [44] Y. Furuta, B. B. Gowen, K. Takahashi, K. Shiraki, D. F. Smee, and D. L. Barnard, “Favipiravir (T-705), a novel viral RNA polymerase inhibitor,” Antiviral Res., vol. 100, no. 2, pp. 446–454, Nov. 2013, doi: 10.1016/j.antiviral.2013.09.015. [45] B. Wang, Y., Fan, G., Salam, A., Horby, P., Hayden, F. G., Chen, C., Pan, J., Zheng, J., Lu, B., Guo, L., Wang, C., & Cao, “Comparative Effectiveness of Combined Favipiravir and Oseltamivir Therapy Versus Oseltamivir Monotherapy in Critically Ill Patients With Influenza Virus Infection,” J. Infect. Dis., vol. 221, no. 10, pp. 1688–1698, 2020, doi: https://doi.org/10.1093/infdis/jiz656. [46] V. Madelain et al., “Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials,” Clin. Pharmacokinet., vol. 55, no. 8, pp. 907–923, Aug. 2016, doi: 10.1007/s40262-015-0364-1. [47] “Faviravir: Favipiravir Leaflet.” [Online]. Available: https://www.aci-bd.com/Brand/Faviravir.pdf. [48] M. Nasir, R. Perveen, S. Sk, K. Talha, and I. Ma, “Systematic Review on Repurposing Use of Favipiravir Against SARS-CoV-2,” Mymensingh Med. J., vol. 29, pp. 747–754, Sep. 2020. [49] “COVID-19 Tedavisine Yönelik Advers Reaksiyon Bildirim Formu,” 2020. [Online]. Available: https://titck.gov.tr/storage/Archive/2020/contentFile/Covid-19 Advers Reaksiyon Bildirim Formu-web yayın_1fea7671-1dba-4e4a-9515-e623be819d6e.pdf. [50] “COVID-19 Advers Reaksiyon (İstenmeyen Etki) Takip Formu,” 2020. [Online]. Available: https://titck.gov.tr/storage/Archive/2020/contentFile/Covid-19 Advers Reaksiyon Takip Formu-web yayın_83840ddb-bbe4-4108-a0c4-58dac7b51de0.pdf. [51] “TITCK Duyuru 3774,” 2020. [Online]. Available: https://www.titck.gov.tr/duyuru/3774. [52] “İlaç Güvenlik İzlem Formu ile Kullanılan ve Kısıtlı Dağıtımda Olan İlaçların Temini,” 2020. [Online]. Available: https://www.titck.gov.tr/duyuru/ilac-guvenlik-izlem-formu-ile-kullanilan-ve-kisitli-dagitimda-olan-ilaclarin-01042020114742. [53] “İlaç Güvenlik İzlem Formu ile Kullanılan ve Kısıtlı Dağıtımda Olan İlaçların Temini Hakkında Duyuru,” 2020. [Online]. Available: https://www.titck.gov.tr/duyuru/ilac-guvenlik-izlem-formu-ile-kullanilan-ve-kisitli-dagitimda-olan-ilaclarin-temini-hakkinda-duyuru-06072020172105. [54] “PHARMACOVIGILANCE IN THE AGE OF COVID-19,” 2020. [Online]. Available: https://www.uppsalareports.org/articles/pharmacovigilance-in-the-age-of-covid-19/. [55] C. Ogar, W. Mathenge, C. Khaemba, and H. Ndagije, “The challenging times and opportunities for pharmacovigilance in Africa during the COVID-19 pandemic,” Drugs Ther. Perspect. Ration. drug Sel. use, pp. 1–4, May 2020, doi: 10.1007/s40267-020-00748-4. [56] R. E. Chandler, D. McCarthy, J.-C. Delumeau, and M. Harrison-Woolrych, “The Role of Pharmacovigilance and ISoP During the Global COVID-19 Pandemic,” Drug Saf., vol. 43, no. 6, pp. 511–512, Jun. 2020, doi: 10.1007/s40264-020-00941-4.