Jarir At Thobari
Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta

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Safety monitoring of chloroquine and hydroxychloroquine in COVID-19 patients in Indonesia on QT prolongation: hospital based monitoring study Jarir At Thobari; Togi Junice Hutadjulu; Tri Asti Isnariani; Umi Sa'adatun Nikmah; Lukman Ade Chandra; Pompini Agustina Sitompul; Anggoro Budi Hartopo; Rizki Amalia Gumilang; Luhur Pribadi; Deva Bachtiar; Anwar Santoso
Indonesian Journal of Pharmacology and Therapy Vol 4 No 1 (2023)
Publisher : Indonesian Pharmacologist Association or Ikatan Farmakologi Indonesia (IKAFI) and Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (287.561 KB) | DOI: 10.22146/ijpther.7148

Abstract

Chloroquine (CQ) and Hydroxychloroquine (HCQ) are the challenging drugs used for COVID-19. Several studies show its beneficial, however, both medications can prolong the QTc interval and increase the risk of patients for torsades de pointes and death. The Tisdale score is identified to have successfully predicted the at-risk population of side effects of these drugs. This study aim to evaluate the QT prolongation caused by the administration of chloroquine and hydroxychloroquine in COVID-19 patients and the association with the treatment outcomes based on their Tisdale score. We conducted an observational study on 213 hospitalized patients with confirmed or suspect COVID-19 in 6 referral hospitals in Indonesia. All baseline demographic such as age and gender, RT-PCR test result, severity of disease, history of cardiovascular disease (myocardial infarction, heart failure, hypertension), serum kalium level at baseline, and the use of medication associated with risk QTc interval prolongation were collected. The Tisdale risk score was used for predicting high-risk patients for QT corrected (QTc) interval prolongation. Out of 213 patients who were treated with CQ/HCQ, there were 60 (28.2%) patients had QTc interval prolongation, included 43 patients (20.2%) who had normal QTc interval at baseline and at the end of treatment had prolong interval; or 17 patients (8.0%) who had QTc interval more than 470 msec at baseline and QTc interval prolongation was worsen at the end of treatment. Several factors, including age more than 50 years, COVID-19 confirm PCR, and had comorbidity heart failure, were statistically significant associated with QTc interval prolongation. The high-risk score of Tisdale score have increased risk significantly on QTc interval prolongation (RR: 2.15, 95%CI 1.07-4.32) and associated with risk of death (RR: 3.50, 95%CI 1.34-9.13) compared to low-risk score. Our findings showed that the treatment of CQ/HCQ in COVID-19 patients is associated with QTc prolongation. The Tisdale score can be used as a valuable tool to predict the COVID-19 patients’ outcome after treatment of these QTc-prolonging drugs.
Early drug-induced hepatotoxicity in newly diagnosed HIV-positive patients on ARV therapy: A retrospective follow-up study of liver function profiles Lukman Ade Chandra; Yanri Wijayanti Subronto; Jarir At Thobari
Indonesian Journal of Pharmacology and Therapy Vol 4 No 2 (2023)
Publisher : Indonesian Pharmacologist Association or Ikatan Farmakologi Indonesia (IKAFI) and Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (217.386 KB) | DOI: 10.22146/ijpther.7817

Abstract

Antiretroviral therapy (ART) is a primary therapeutic modality for managing individuals with Human Immunodeficiency Virus (HIV) infection, and its efficacy has been established. However, the safety profiles of ART need to be continually monitored, including early elevated liver function test (LFT) after antiretroviral (ARV) initiation. This study aimed to assess the incidence of abnormal LFT among HIV-positive patients receiving initial ARV and to identify factors associated with abnormal LFT. A retrospective cohort study without a control group summarised medical records from Dr Sardjito General Hospital, Yogyakarta between January 2014 and December 2021. The study subjects were adult HIV patients taking their first ARV and underwent follow-up visits for at least two weeks. Study outcomes were LFT levels, abnormal LFT, and factors associated with abnormal LFT during follow-up visits at 2 wk, 6 mo, and 12 mo. Univariate and multivariate analyses will be performed with a significance level of p<0.05. A total of 137 subjects with 203 visits were retrieved from medical records. The subjects' mean age was 33.4 years, predominantly male, younger, unmarried, in the early stage of HIV infection, and without comorbidities. The findings showed a significant increase in alanine transaminase (ALT) at all three follow-up visits: 2 wk (p=0.02), 6 mo (p=0.003), 12 mo (p=0.001) and an increase in aspartate aminotransferase (AST) after 6 mo (p=0.007) and 12 mo (p=0.04). Abnormal LFT levels (AST and/or ALT) were observed in 23.4% of patients after a normal baseline, with ALT increase being more common. Furthermore, homosexuality was identified as a significant independent factor associated with abnormal LFT (AOR=3.1; 95% CI 1.27-7.51; p=0.01). The findings indicate exceptionally elevated LFT levels and the occurrence of abnormal LFTs among HIV-positive patients initiating ARVs. The increase in abnormal LFTs was significantly associated with patients identifying as homosexual, where hepatitis co-infection may be a contributing factor. The limited study design and measured variables warrant further investigation.