Page 100 - 80 guidelines for the treatment of malaria_opt

N
N
CI
2
CH 3
HN
CH 3
H
NH
2
CH 3
F
H 3 C
F
F
F H 3 C N CH 3 CI HN OH N CH 3 CH 3 H N H 3 C O S O N N O N O CH 3 H N N N 2 H 3 C CI
F
N O O O
O C O C O C
F O O O
ÿ O CH 3 Guidelines for the treatment of malaria – 2 edition O O CH 3
CH 3
nd
O
H H H H 3 C H H HO H H
HO O O O
H
H a3.7 lumefantrine (benflumetol) H
HN CH 3 CH 3 O CH 3
Molecular weight: 528.9
Lumefantrine belongs to the aryl
H 3 C H 3 C CI
aminoalcohol group of antimalarials,
which also includes quinine, CH 3
O O
O C O C NH 2
HN
O O mefloquine and halofantrine. It
CH 3 CH 3 CI CI has a similar mechanism of action. N
O O
H H H H Lumefantrine is a racemic fluorine
H 3 C H 3 C
HO H 3 C O derivative developed in China. It is
O
H H only available in an oral preparation
CH 3 CH 3 H 3 C N
OH coformulated with artemether.
This ACT is highly effective against
multidrug resistant P. falciparum.
Formulations
CI CI
H H H Available only in an oral preparation coformulated with artemether.
N N N CH 3 CI O
H • Tablets containing 20 mg of artemether and 120 mg of lumefantrine.
NH
NH
CH 3
H N S NH 2
2
NH NH CH 3
CI Pharmacokinetics H H CH 3 O
H
O N N N
H Oral bioavailability is variable and is highly dependant on administration with fatty
foods (38,49). Absorption increases by 108% after a meal and is lower in patients with
OH acute malaria than in convalescing patients. Peak plasma levels occur approximately 10 h
O after administration. The terminal elimination half-life is around 3 days.
Toxicity
Despite similarities with the structure and pharmacokinetic properties of halofantrine,
H 2 C H H 3 C CH 3 lumefantrine does not significantly prolong the electrocardiographic QT interval, and has
OH
CI
O
CH 3
O
HO CH 3 H N no other significant toxicity (50). In fact the drug seems to be remarkably well tolerated. CH 3
O
OH
O
OH
N
OH Reported side effects are generally mild – nausea, abdominal discomfort, headache and
NH
2
N dizziness – and cannot be distinguished from symptoms of acute malaria. H N H
H 3 C O
HO H NH 2 CH 3
Drug interactions OH H HO S
OH H H
O OH O OH O O
H 3 C
H 3 C The manufacturer of artemether-lumefantrine recommends avoiding the following: grapefruit OH
OH
HO
N
juice; antiarrhythmics, such as amiodarone, disopyramide, flecainide, procainamide and
H 3 C
CH 3
N quinidine; antibacterials, such as macrolides and quinolones; all antidepressants; antifungals
such as imidazoles and triazoles; terfenadine; other antimalarials; all antipsychotic drugs;
and beta blockers, such as metoprolol and sotalol. However, there is no evidence that
coadministration with these drugs would be harmful.
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