Amodiaquine

Observational studies

Amodiaquine has been suggested to be effective and safe in pregnancy, but its use has been limited because of previous reports of neutropenia and lymphopenia. Amodiaquine has been studied alone or in combination with sulfadoxine + pyrimethamine in 900 women with P. falciparum malaria in Ghana, who were randomly assigned to chloroquine (n = 225), sulfadoxine + pyrimethamine (n = 225), amodiaquine (n = 225), or amodiaquine plus sulfadoxine + pyrimethamine (n = 225) [ ]. The primary outcome measure was parasitological failure at day 28 of treatment. Parasitemia, hemoglobin concentration, white blood cell count, and liver function were assessed on days 3, 7, 14, and 28, and reports of adverse events were solicited at each visit. At day 28, parasitological failure was 14%, 11%, 3%, and 0% in the women assigned chloroquine, sulfadoxine + pyrimethamine, amodiaquine, and amodiaquine with sulfadoxine + pyrimethamine respectively. General weakness, vomiting, dizziness, and nausea were the most frequent adverse effects and were more common in those who took amodiaquine and amodiaquine with sulfadoxine + pyrimethamine than in those who took sulfadoxine. However, there were no major changes in the white blood cell, bilirubin, and liver enzyme profiles during or at the end of the study. Of the 900 women, 711 (79%), were followed up to delivery and for 6 weeks after. The proportion with peripheral parasitemia was significantly lower in those who took amodiaquine + sulfadoxine than in those who took chloroquine (2% versus 10%), but there was no significant difference in the occurrence of placental parasitemia across the four treatment groups. No maternal deaths were recorded and seven babies had extra digits (one chloroquine, five amodiaquine, and one amodiaquine with sulfadoxine + pyrimethamine).

This suggests that amodiaquine, alone or in combination with sulfadoxine + pyrimethamine, is associated with minor adverse effects but is efficacious in malaria in pregnancy in places where falciparum malaria is still sensitive to these drugs, as is the case in much of West Africa.

Comparative studies

Amodiaquine and chloroquine have been compared in an open, randomized trial in uncomplicated falciparum malaria in Nigerian children [ ]. The doses were amodiaquine (n = 104) 10 mg/kg/day for 3 days and chloroquine (n = 106) 10 mg/kg/day for 3 days. After 28 days, the cure rate was significantly higher with amodiaquine than chloroquine (95% versus 58%). The rates of adverse events, most commonly pruritus (10%) and gastrointestinal disturbances (3%), were similar in the two groups. Cross-resistance between the two aminoquinolines is common, and there are concerns regarding toxicity of amodiaquine with repeated use.