Hacettepe University Journal of the Faculty of Pharmacy Review Article Volume 41 / Number 2 / July 2021 / pp. 93-101 Pharmacovigilance Activities in the Treatment of COVID-19 COVID-19 Tedavisinde Farmakovijilans Aktiviteleri Ozal, Gizem1 Orcid: 0000-0003-1928-566X, ABSTRACT Inceoglu, Bilge1 The unexpected pandemic initiated by the new coronavirus 2019 (2019-nCoV) Orcid: 0000-0003-1172-1711, caused severe panic among people around the world since December 2019. Cor- Suzgec, Sezen1 onavirus disease 2019 (COVID-19) has wreaked havoc, and Health Authorities Orcid: 0000-0001-5865-8110, have started to make announcements and studies have been started quickly, for Duran, Nur Hilal1 effective treatment and vaccination. In studies, drugs that reduce the symptoms Orcid: 0000-0001-7160-4408, of COVID-19 and alleviate the course of the disease have been used. In addition Topaloglu, Gizem1 to the effects of these promising drugs, adverse events and multiple drug interac- Orcid:0000-0003-0580-5337, tions have begun to appear all over the world, as well as in our country. Therefore, Arda, Burcu Eda1 pharmacovigilance is of particular importance during the COVID-19 pandemic. Orcid: 0000-0002-6767-9092, Health authorities have been taking additional actions and measures to carry out Erkoc, Gozdenur1 adverse effects monitoring and risk minimization activities of drugs. In our study, Orcid: 0000-0001-6315-8807, we have reviewed the measures taken related to COVID-19 in Turkey and around Gulhan, Ali1 the world along with safety of drugs used to treat COVID-19 and pharmacovigi- Orcid: 0000-0001-7460-0576 lance activities during the pandemic. Keywords: SARS-CoV-2, COVID-19, Pharmacovigilance, Drug Safety, Ad- 1 Excelya Medikal Araştırma ve verse Event Danışmanlık AŞ, Department of Pharmacovigilance and Safety, Istanbul, ÖZET Turkey Aralık 2019’dan bu yana yeni tip koronavirüsün (2019-nCoV) başlattığı beklen- medik 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 Corresponding author: çalışmalara hızlıca başlanmıştır. Çalışmalarda, COVID-19 semptomlarını azaltıcı Burcu Eda Arda Excelya Medikal Araştırma ve Danışmanlık ve hastalığın seyrini hafifletici ilaçlar kulanılmaya başlanmıştır. Umut vadeden bu AŞ, Department of Pharmacovigilance and ilaçların etkilerinin yanısıra, tüm dünyada ve ülkemizde advers olaylar ve çoklu ilaç Safety, İstanbul etkileşimleri görülmeye başlanmıştır. Bu nedenle, COVID-19 pandemi sürecinde E-mail: [email protected] https://orcid.org/0000-0002-6767-9092 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 güvenliği ve pandemi sürecindeki farmakovijilans aktivitelerini derlemektir. Anahtar Kelimeler: SARS-CoV-2, COVID-19, Farmakovijilans, İlaç Güvenliliği, Received date : 26.03.2021 Advers Olay Accepted date : 05.07.2021 Hacettepe University Journal of the Faculty of Pharmacy 1. Introduction demic was declared on March 11, 2020, as it was al- ready spread to 113 countries outside of China. The The pneumonia cases with unknown etiology started most important reason for COVID-19 to transform to be reported in Wuhan, Hubei Province, China in into a pandemic is the ease of its transmission. The December 2019 [1]. The Chinese authorities identi- ways of transmission are direct contact, indirect con- fied a new type of coronavirus (2019-nCoV) which tact, aerosol and droplet [9]. was not previously detected in humans on January 7th, 2020 [2]. The virus renamed as severe acute As it did in all countries, coronavirus began to spread respiratory syndrome coronavirus 2 (SARS-CoV-2) across Turkey. Ministry of Health announced the due to its close similarity to SARS-CoV. Then, 2019- first case on March 11, 2020. According to the infor- nCoV disease was accepted as COVID-19 [1]. Coro- mation reported by governments, 30,372,127 people naviruses are a fairly large family of viruses, with were infected in the world and 949,486 of them died subtypes found in humans that can be transmitted as of October 1st. In Turkey, 7,315 deaths were re- from one person to another, often causing mild in- ported out of 298,039 cases, as of October 1st [9,10]. fection, such as the common cold. However, many coronavirus subtypes, detected in animals, can cause 2. Pharmacovigilance Activities of severe illness in humans when transmitted from animals to humans [1]. The viruses that caused the Authorities During Covid-19 Pandemic SARS-CoV outbreak in 2002 and the Middle East Pharmacovigilance system has been greatly affected respiratory syndrome coronavirus (MERS-CoV) by the COVID-19 pandemic, like every part of the outbreak in 2012 also belong to the same family healthcare systems in the world. Health authorities named Coronaviridae [3,5]. have published various announcements about drug SARS-CoV-2, like other coronaviruses, is an en- safety almost every day to ensure that pharmacovigi- veloped, single-stranded RNA virus [6]. One of the lance processes are carried out correctly and com- structural protein types of the coronaviruses, spike pletely. Regulatory authorities also play a very im- (S) protein, is important for infection mechanism be- portant role in pharmacovigilance during the COV- cause of its assistance viral entry into the host cell by ID-19 pandemic. binding to angiotensin-converting enzyme 2 (ACE2) receptor [7,8]. SARS-CoV and SARS-CoV-2 are WHO (World Health Organization) has published similar because they both use S protein and ACE2 Solidarity Clinical Trial for COVID-19 Treatments as a receptor [3]. [11]. The spectrum of illness caused by COVID-19 in EMA (European Medicines Agency) announced the humans can range from the common cold (mild res- first notification about COVID-19 entitled “Guid- piratory symptoms) to lethal symptoms which are ance for medicine developers and other stakeholders associated with severe pneumonia, acute respiratory on COVID-19” on the 4th of February. More than distress, and renal failure [1,6]. It can also cause en- a hundred announcements were shared during the teric, hepatic, nephrotic and neurological involve- 7-month pandemic period after the first notification. ment in humans [1]. The most frequent symptoms These announcements were related to guidance for of COVID-19 infection are fever, dry cough, myal- medicine developers and other stakeholders, avail- gia, fatigue, and dyspnea [1,7]. Additional symptoms ability of medicines, treatments and vaccines and can be seen as headache, sore throat, nasal discharge, public-health advice. EMA has explained how to loss of sense of smell and taste, and diarrhea [1]. act on pharmacovigilance processes and inspections Cases with severe symptoms and deaths are gener- with the announcements it has published throughout ally seen in elderly patients or patients with concom- the pandemic [12]. itant systemic diseases like hypertension, diabetes, Meanwhile, FDA (U.S. Food & Drug Administra- cardiovascular disease, cancer, chronic lung diseases tion) announced the first notification about COV- and other immunosuppressive conditions [1]. Even ID-19 on the 27th of January. According to this though symptoms are various, there is a chance that notification, FDA published key activities to the patients may be asymptomatic. advancement of novel coronavirus medical counter- Due to the speed and severity of the virus, the pan- measures. The announcements are published almost Volume 41 / Number 2 / July 2021 / pp. 93-101 94 Arda et al. Hacettepe University Journal of the Faculty of Pharmacy every day to include recent information and updates 3. Pharmacological Therapies Considered on the COVID-19 pandemic [13]. For Treatment of Covid-19 The first announcement shared by ANSM (French Agency for the Safety of Health Products) about The unexpected epidemic initiated by COVID-19 has caused severe panic among people around the COVID-19 on the 3rd of March was related to mask world, hence scientists and doctors have started drug stock demand [14]. A special system established by and vaccine studies to treat COVID-19, whilst also ANSM aimed to monitor drug-related adverse reac- testing the efficacy and safety of used drugs [19]. tions more carefully. With this system, the focus was on the follow-up monitoring of drug-related adverse Drug development is a multi-step process and typi- reactions, as well as medication errors and overdose cally requires more than five years to ensure the cases [15]. safety and effectiveness of the new compound [20]. Several national regulatory agencies, such as EMA In the UK, the situation regarding pharmacovigilance and FDA, approved procedures to expedite clinical processes in pandemic started by MHRA (Medicines testing [21,22]. and Healthcare products Regulatory Agency) an- Currently, there is no proven effective treatment nouncing the first notification about COVID-19 on or vaccine against COVID-19 infection. Therefore, the 22nd of January. MHRA explained the monitor- no standard therapy is available. A large number of ing of the coronavirus situation in Wuhan. This noti- drugs are used empirically based on experience and fication was mainly related to travel restrictions [16]. availability. Studies