Drug interactions
The 8-aminoquinolines have important pharmacokinetic and pharmacodynamic
interactions with other structurally related antimalarial drugs.
Coadministration of mepacrine (atebrin, quinacrine) substantially
increases plasma concentrations of pamaquine and also reduces
tolerability. It substantially increases methaemoglobinaemia associated
with pamaquine (33). Chloroquine, piperaquine and pyronaridine all
increase plasma concentrations of primaquine by approximately 20%, but
they do not affect tolerability (34). Pamaquine and primaquine radical
curative activity is increased by concomitant (but not sequential)
administration with quinine (35, 36). Chloroquine has also been shown to
potentiate the radical curative efficacy of primaquine. During the
clinical development of primaquine it was observed that coadministration
of primaquine with quinine or chloroquine attenuated the consequent
methaemoglobinaemia. This was not observed in comparable studies with
pamaquine (plasmoquine) (Figure 5).
However larger, more recent, studies have not confirmed this early
finding (Figure 6). They do not suggest any substantial differences
between methaemoglobin levels with or without concomitant medicines
(quinine, chloroquine, artesunate, artesunate-pyronaridine,
dihydroartemisinin-piperaquine have all been evaluated), nor do they
suggest differences between methemoglobin levels in the treatment of
malaria (in which steady state methaemoglobin levels are reached well
after resolution of symptoms), or in healthy subjects. Thus the impact
of blood schizontocides on 8-aminoquinoline induced methaemoglobineamia
is specific to the drugs and is not a general class effect.