Table 1 |
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Key clinical studies evaluating the safety of the six-dose regimen of AL. |
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| Study number |
Design |
Comparator |
Patients |
Number given AL compared with total |
Participating countries |
Key safety findings |
|
|
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| van Vugt et al 1999 [6] |
Randomized, double-blind |
Six-dose regimen |
Adults & children (>2 years) |
120 out of 359† |
Thailand |
Possible treatment-related AEs were reported by 16.7% of patients. These AEs could
also have been related to malaria and were mild or moderate in severity. No neurological
or cardiac safety issues were identified. |
| van Vugt et al 2000 [7] |
Randomized, open-label |
MAS* |
Adults & children (≥ 2 years) |
150 out of 200 |
Thailand |
Most AEs considered drug-related were mild or moderate in severity. Possibly related
AEs occurred at a frequency of 22% in the AL group compared with 46% in the MAS group.
In the AL group 6% had nervous system AEs compared with 34% in the MAS group (relative
risk: 0.18; p < 0.0001). Gastrointestinal AEs were also less frequent in the AL compared
with MAS groups (12.7% vs 26%; relative risk: 0.49; p < 0.043). No ECG abnormalities
were identified. |
| Lefèvre et al 2001 [8] |
Randomized, open-label |
MAS* |
Adults & adolescents (≥ 12 years) |
164 out of 219 |
Thailand |
Nearly 90% in both treatment groups reported treatment emergent signs/symptoms and
these were of mild or moderate severity. 18.3% of patients taking AL and 21.8% of
patients taking MAS reported gastrointestinal symptoms while 27.4% and 16.4% of patients,
respectively reported headache, dizziness and sleep disorder. Skin reactions were
reported by 4.9% of patients taking AL and 3.6% of patients taking MAS. There were
no cardiac complications and no significant renal, hepatic or haemopoietic dysfunction. |
| Falade et al 2005 [9] |
Open-label |
Nil |
Infants & children (5 to 25 kg) |
310 |
Kenya, Tanzania, Nigeria |
The most commonly reported AEs were cough, anaemia, anorexia, vomiting and diarrhoea.
Some differences in AEs were seen in the different body weight groups but as these
were generally mild, differences were not considered clinically relevant. Only one
patient had a SAE (urticaria) that was considered to be related to study medication
and this event resolved when treatment was withdrawn. No cardiac safety issues were
identified and there were no significant abnormal laboratory values associated with
AL treatment. |
| Hatz et al 2008 [10] |
Open-label |
Nil |
Adult, non-immune travellers |
165 |
EU, Colombia |
Treatment was well tolerated and most AEs were mild or moderate in severity. The most
frequently reported AEs were headache, insomnia, diarrhoea, nausea and vomiting and
these AEs (along with anorexia, vertigo and chills) were most probably related to
signs and symptoms of malaria. No allergic reactions were reported in any of the patients.
There were few SAEs and none of these were considered related to AL. No significant
effects were observed during ECGs and there were no significant effects seen with
regard to laboratory parameters. |
| Abdulla et al 2008 [11] |
Randomized, investigator-blind |
Dispersible formulation of AL |
Infants & children (5 to <35 kg) |
452 out of 899 |
Kenya, Tanzania, Mali, Benin, Mozambique |
There was no difference in the pattern of AEs seen in patients who received treatment
with crushed AL tablets compared with those who received the dispersible formulation.
No new or unexpected AEs were identified and the most commonly reported AEs were also
related to malaria. The most common drug-related AE was vomiting; this was more frequently
reported in the lowest weight category. The number of SAEs was low (1-2% in both groups)
and most of these were infections. There were no signs of ototoxicity. There were
no clinically relevant findings or differences between study groups for ECG assessments,
vital signs, or laboratory parameters. |
|
|
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|
*Study was not designed to compare artemether/lumefantrine with mefloquine/artesunate †Artemether/lumefantrine over 60 hours AE: adverse event;AL: artemether/lumefantrine; ECG: electrocardiogram; MAS: mefloquine/artesunate; SAE: serious adverse event; vs.: versus |
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|
Falade and Manyando Malaria Journal 2009 8(Suppl 1):S6 doi:10.1186/1475-2875-8-S1-S6 |
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