Comparison of QTc interval changes in drug-resistant tuberculosis patients on delamanid-containing regimens versus shorter treatment regimens

Article type: Research Article

Authors: Jefman Efendi Marzuki, H.Y.^{a; b} | Nafrialdi, Nafrialdi^c | Sawitri, Neni^d | Sugiri, Yani Jane^e | Gusti Agung Ayu Putu Sri Darmayani, I^{f; g} | Ascobat, Purwantyastuti^c;

Affiliations: [a] Program Pendidikan Dokter Spesialis Farmakologi Klinik, FK UI, Jakarta, Indonesia | [b] Fakultas Kedokteran Universitas Surabaya, Surabaya, Indonesia | [c] Departemen Farmakologi dan Terapeutik, FK UI, Jakarta, Indonesia | [d] Rumah Sakit Paru M. Goenawan Partowidigdo, Gadog Cisarua, Indonesia | [e] RSUD Dr. Saiful Anwar, Malang, Indonesia | [f] Program Pendidikan Dokter Spesialis Farmakologi Klinik, FK UI, Jakarta, Indonesia | [g] Badan Pengawas Obat dan Makanan, Jakarta, Indonesia

Correspondence: [*] Address for correspondence: Prof. Dr. Purwantyastuti, M.Sc, Sp.F.K., Departemen Farmakologi dan Terapeutik, FK UI, Jalan Salemba Raya Jakarta, 10430, Indonesia. E-mail: [email protected]

Abstract: BACKGROUND:Delamanid (DLM) is a relatively new drug for drug-resistant tuberculosis (DR-TB) that has been used in Indonesia since 2019 despite its limited safety data. DLM is known to inhibit hERG potassium channel with the potential to cause QT prolongation which eventually leads to Torsades de pointes (TdP). OBJECTIVE:This study aims to analyse the changes of QTc interval in DR-TB patients on DLM regimen compared to shorter treatment regimens (STR). METHODS:A retrospective cohort was implemented on secondary data obtained from two participating hospitals. The QTc interval and the changes in QTc interval from baseline (ΔQTc) were assessed every 4 weeks for 24 weeks. RESULTS:The maximum increased of QTc interval and ΔQTc interval were smaller in the DLM group with mean difference of 18,6 (95%CI 0.3 to 37.5) and 31.6 milliseconds (95%CI 14.1 to 49.1) respectively. The proportion of QTc interval prolongation in DLM group were smaller than STR group (RR=0.62; 95%CI 0.42 to 0.93). CONCLUSION:This study has shown that DLM regimens are less likely to increase QTc interval compared to STR. However, close monitoring of the risk of QT interval prolongation needs to be carried out upon the use of QT interval prolonging antituberculoid drugs.

Keywords: Anti-tuberculoid, pharmacovigilance, QT prolonged, long QT syndrome

DOI: 10.3233/JRS-230024

Journal: International Journal of Risk & Safety in Medicine, vol. 35, no. 2, pp. 181-190, 2024