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Table 3 Published studies with the six-dose AL regimen in Asia

From: Safety profile of Coartem®: the evidence base

Authors Country Design and patient population Comparators (no. of patients) Results
South-East Asia     
Krudsood et al 2003 [33] Thailand Randomized, open-label, single centre in adults AL (n = 41) DNP (n = 89) No deterioration in clinical or biochemical responses occurred after treatment with AL or DNP. Minor symptoms (nausea, headache, and dizziness) were seen in both groups. These could not be differentiated from malaria signs and symptoms as they resolved simultaneously with fever 1-4 days after treatment. There were no SAEs or deaths, and no neurological or neuropsychiatric manifestations were seen during treatment or during the 28-day follow-up period.
Stohrer et al 2004 [34] Laos Randomized, open-label, hospital and community-based study in adults and children (≥ 10 kg) AL (n = 53) MAS (n = 55) Most of the recorded treatment emergent symptoms/signs (TESS) on day 0 and day 3 were mild or moderate in severity, and were symptoms typical of malaria. There were no significant differences between treatment groups in the incidence of gastrointestinal disorders like abdominal pain, nausea, vomiting, diarrhoea or anorexia (12.8% for AL vs. 12.0% for MAS), or nervous system disorders like headache, dizziness, weakness, or sleep disorder (29.8% for AL vs. 41.5% for MAS). Apart from severe diarrhoea (1 patient in the AL group) and sleep disorder and dizziness (1 patient in the MAS group), no other potentially drug-related AEs were reported.
Mayxay et al 2004 [35] Laos Randomized, open-label, single centre, in adolescents and adults (12-19 years) AL (n = 110) MAS (n = 110) CQSP (n = 110) The proportion of patients with symptoms and signs before treatment, which may subsequently be confused with drug-related AEs, did not differ significantly between the 3 groups. The proportion of patients with ≥ 1 potential side-effect was higher in the MAS group (52%) than in the CQSP group (44%) or the AL group (27%). Three patients in the MAS group had serious neuropsychiatric effects following treatment, 1 patient developed fever and a Glasgow coma score of 8/15 due to the presence of gametocytes on day 15 after CQSP and 1 patient had hallucinations and uncharacteristic anxiety on day 20.
Ratcliff et al 2007 [36] Indonesia Randomized, open-label, 2-centre in children (body weight ≥ 10 kg) and adults AL (n = 387) DP (n = 387) AEs were assessed in patients without the symptom at enrolment and were similar between groups apart from a two-fold increased risk of diarrhoea on days 1 and 2 in more patients receiving DP compared with AL (95% CI 1.3-3.3; p = 0.003). By day 7, the risk of diarrhoea was 5% in both treatment groups. Although 35% of patients developed a headache on days 1 and 2 after DP compared with 23% of patients given AL, the difference was not significant as headache was a common symptom at presentation.
Hutagalung 2005 [37] Thailand Randomized, open-label, 2-centre, in children (>10 kg) and adults AL (n = 245) MAS (n = 245) AL and MAS were well tolerated. Vomiting of one or more doses of drug occurred in 2.1% in the AL group and 0.8% of the MAS group (relative risk, 2.5; 95% CI, 0.5-12.7; p = 0.45). The rates of early vomiting (within one hour) of dosing were very low (around 2%) and did not differ between groups. The most commonly reported and possibly drug-related AEs were effects on the gastrointestinal (abdominal pain, anorexia, nausea, diarrhoea and vomiting more than 1 hour after dosing) and central nervous system (headache, dizziness). There were fewer AEs in the AL group compared with the MAS group, although this was not statistically significant. No SAEs were reported.
South Asia     
van den Broek et al 2005 [38] Bangladesh Randomized, open-label, single centre, in adults and children (≥ 1 year) AL (n = 121) MAS (n = 121) CQSP (n = 122) All treatments were well tolerated. Mild AEs reported during the 3 days of treatment were headache, vomiting, nausea and dizziness. The frequency of these AEs was generally higher after MAS compared with AL (p < 0.05). After CQSP treatment, complaints were of intermediate frequency, but vomiting occurred more in this group. Other AEs were anorexia, skin itching and deafness with CQSP, sleeplessness, anorexia, skin itching/rash, epigastric pain and excessive sweating with MAS and blurred vision and anorexia with AL. No severe AEs were observed.
Thapa et al 2007 [39] Nepal Randomized, open-label, single centre, in adults and children (>5 years) AL (n = 66) SP (n = 33) The most commonly reported symptoms at presentation apart from fever were headache (97% in the AL group and 88% in the SP groups), nausea (42% and 64%, respectively), and vomiting (39% and 46%, respectively). Other gastrointestinal, neurological, musculoskeletal, respiratory, and dermatologic complaints were much less frequent. During treatment, <12.5% of patients reported one or more symptoms, with the majority of mild intensity, and no significant differences seen between groups. There were no group-specific differences in changes in pulse or blood pressure during initial therapy. ECGs were conducted in 10 patients in the AL group and 8 patients in the SP group and no changes in QTc were observed during treatment with either drug.
  1. AL: artemether/lumefantrine; ECG: electrocardiogram; SP: sulphadoxine/pyrimethamine; CI: confidence interval; CQSP: Chloroquine/sulphadoxine/pyrimethamine; DP: Dihydroartemisinin/piperaquine; DNP: dihydroartemisinin/napthoquine/trimethoprim; MAS: mefloquine/artesunate; vs.: versus