Page 89 - 80 guidelines for the treatment of malaria_opt

ANNEX 3. Pharmacology of antimalarial medicines

a3.2 amodiaquine

Molecular weight: 355.9
Amodiaquine is a Mannich base
CI N CI N
4-aminoquinoline with a mode of
action similar to that of chloroquine H N N
2
(interference with parasite haem N N CH 3
O
O
S
HN CH 3 HN detoxification). It is effective against CH 3 N
N CH 3 N O
some chloroquine-resistant strains of A3 NH
H
OH CH 3 P. falciparum, although there is cross- O CH 3 2 CI
H N
2
resistance.
N CH 3
Formulations
H 3 C
• Tablets containing 200 mg of amodiaquine base as hydrochloride or 153.1 mg of base
as chlorohydrate.
F
Pharmacokinetics H 3 C H 3 C
H 3 C
F F
F
F Amodiaquine hydrochloride is readily absorbed from the gastrointestinal tract. It is
N O O C O O C O O C
F rapidly converted in the liver to the active metabolite desethylamodiaquine, which O
O
O
contributes nearly all of the antimalarial effect (10). There are insufficient data on the CH 3
ÿ
CH 3
CH 3
O
terminal plasma O O O
H elimination half-life of desethylamodiaquine. Both amodiaquine
H H H H H H
H 3 C
and desethylamodiaquine have been detected in the urine several months after HO
HO O O O
administration. H H H
HN CH 3 CH 3 O CH 3
Toxicity
The adverse effects of amodiaquine are similar to those of chloroquine. Amodiaquine
CI
H 3 C is associated with much less pruritus and is more palatable than chloroquine, but is
H 3 C
associated with a much higher risk of agranulocytosis and, to a lesser degree, of hepatitis CH 3
O
O Oylaxis (11). The risk of a serious adverse reaction with prophylactic use NH
O C when used for proph C 2
O (which is no longer recommended) appears to be between 1 in 1000 and 1 in 5000. It is not HN
O
CH 3 CH 3 CI CI N
O clear whether the risks are lower when amodiaquine is used to treat malaria. Following
O
H H H H
overdose cardiotoxicity appears to be much less frequent than with chloroquine. Large H 3 C
H 3 C
O
H 3 C
HO doses of amodiaquine have been reported to cause syncope, spasticity, convulsions and O
H H
involuntary movements. H 3 C N
CH 3 CH 3
OH
Drug interactions
There are insufficient data.
CI CI
H H H
N N N CH 3 CI O
H NH NH CH 3 H N S NH
NH NH CH 3 75 2 2
CI H H H CH 3 O
O N N N
H
OH
O
H 2 C H H 3 C CH 3 OH CI
HO CH 3 H N OH O O O CH 3 O CH 3
OH OH N
NH N
N 2 H H
H 3 C O
HO H NH 2 CH 3
OH H HO S
OH H H
O OH O OH O O
H 3 C H 3 C OH N HO OH
H 3 C CH 3
N