Journal
SAUDI PHARMACEUTICAL JOURNAL
Volume 30, Issue 5, Pages 605-612Publisher
ELSEVIER
DOI: 10.1016/j.jsps.2022.02.010
Keywords
Atazanavir-ritonavir; Artemether-lumefantrine; Cardiotoxicity; LUTH
Categories
Funding
- BRAINS (Building Research and Innovation in Nigeria Science) [D43TW010134]
- National Institute of Health (NIH)
- Fogarty International Centre of the National Institutes of Health [D43TW010134]
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This study evaluated the interaction between artemether-lumefantrine (AL) and atazanavir-ritonavir (ATVr) in patients with HIV infection and malaria comorbidity, focusing on the cardiotoxicity and other adverse effects. The results showed that concomitant administration of AL and ATVr could potentially have cardiotoxic effects but did not lead to clinically significant renal, blood, or liver toxicities.
The interplay of artemether-lumefantrine (AL) and atazanavir-ritonavir (ATVr) with Cytochrome P (CYP) 3A4 isoenzyme and QTc-interval may spawn clinically significant drug interactions when administered concomitantly. Cardiotoxicity and other adverse effects associated with interaction between AL and ATVr were evaluated in patients with HIV infection and malaria comorbidity. In a two-arm parallel study design, six doses of AL 80/480 mg were administered to 20 participants [control-arm (n = 10) and ATVrarm (n = 10)], having uncomplicated Falciparum malaria, at intervals of 0, 8, 24, 36, 48 and 60 h respectively. Participants in the control arm took only AL while those in ATVr-arm took both AL and ATVr-based ART regimen. Electrocardiography, adverse events monitoring and blood tests were carried out for each of them at pre and post doses of AL. Data obtained were analyzed. QTc-interval was significantly increased in the ATVr-arm (0.4079 +/- 0.008 to 0.4215 +/- 0.007 s, p = 0.008) but not in the control-arm (0.4016 +/- 0.018 to 0.4024 +/- 0.014 s, p = 0.962). All values were, however, within normal range [0.36 - 0.44 / 0.46 s (male/ female)]. General body weakness and chest pain were new adverse events reported, at post-dose of AL, in the ATVr-arm but not in the control-arm. There was no significant change (p > 0.05) in the plasma levels of creatinine, alanine aminotransferase, aspartate aminotransferase and hemoglobin at post-dose compared to pre-dose of AL in both arms of study. Concomitant administration of artemether-lumefantrine with atazanavir-ritonavir-based regimen is potentially cardiotoxic but not associated with clinically significant renal, blood nor liver toxicities. They must be used with caution. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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