Safety and tolerability of artesunate-amodiaquine, artemether-lumefantrine and quinine plus clindamycin in the treatment of uncomplicated Plasmodium falciparum malaria in Kinshasa, the Democratic Republic of the Congo

Abstract

IntroductionArtemisinin-based combination therapy is currently the best option for the treatment of uncomplicated malaria. Quinine is recommended as a rescue treatment. Safety information during repeated treatment with the same drug is scarce. We report safety data from the Quinact randomized clinical trial (RCT) that was designed to assess efficacy and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and quinine+clindamycin (QnC).MethodologyMales and females aged 12 to 59 months with uncomplicated malaria were treated with ASAQ and followed up during 42 days (preRCT). Clinical failures were randomized to one of the 3 treatments and followed up for 28 days (RCT). Subsequent failures were repeatedly treated with ASAQ several times as needed (postRCT1, postRCT2 and so on) until a 28-days follow up period without parasitaemia.ResultsEight hundred and sixty-five, 242 and 64 patients were recruited respectively in preRCT, RCT and postRCTs. In preRCT, 433 (50.0%) patients experienced at least one drug-related adverse event (AE). The most reported AEs were anorexia (22.9%), asthenia (19.4%), and abnormal behavior (14.6%). Twenty-nine AEs (3.5%) were reported to be severe. In RCT, at least one drug-related AE was reported in 54.7%, 21.5% and 40.0% of patient randomized respectively to ASAQ, AL and QnC (p<0.001). During postRCT1 (n = 64), postRCT 2 (n = 17) and postRCT3 (n = 7), respectively 32.8%, 35.3% and 71.4% of patients experienced at least one drug-related AE. Three serious adverse events occurred but not judged related to study medication.ConclusionThe proportion of AEs did not increase over the treatment courses with ASAQ. However, continuous monitoring is important.

Efficacy of Quinine Plus Clindamycin Versus Artemether-Lumefantrine For The Treatment of Uncomplicated Plasmodium Falciparum Malaria In Kenyan Children (CLINDAQUINE): An Open-Label Randomised Trial

“…In our study, the combination of quinine with clindamycin was well tolerated and had a comparable safety pro le to artemether-lumefantrine. These ndings are similar to those of the QUINACT study [17,23]. Children treated using quinine plus clindamycin were more likely to develop severe adverse events associated with worsening of the malaria infection.…”

Drug-induced hypersensitivity to artemisinin-based therapies for malaria

“…Hypersensitivity drug reactions (HDRs) are, in contrast to most other adverse drug reactions, mediated by specific immunological pathways and are considered largely independent of the administered dose or pharmacological action [27]. Cases of allergic reaction following treatment with artemisinin derivatives have consistently been reported since the first clinical trials systematically evaluating artemisinins [5,19,[28][29][30][31][32][33][34][35].…”

Efficacy and safety of artesunate–amodiaquine and artemether–lumefantrine and prevalence of molecular markers associated with resistance, Guinea: an open-label two-arm randomised controlled trial

“…In line with these recommendations, sub-Saharan African countries have initiated the surveillance of the efficacy and safety of anti-malarial drug treatments to prevent parasite resistance [7][8][9][10]. In Tanzania, a study assessing the efficacy and safety of AL for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of artemisinin resistance molecular markers found high efficacy and safety of AL and no known artemisinin resistance pfk13 mutations [11].…”