[Pg 36]
Treatment of uncomplicated Plasmodium falciparum malaria
Factors associated with altered drug exposure and treatment
response:
• Decreased exposure to lumefantrine has been documented in
young children (<3 years)as well as pregnant women, large adults, patients
taking mefloquine, rifampicin or efavirenz and in smokers. As these target
populations may be at increased risk for treatment failure, their responses to
treatment should be monitored more closely and their full adherence ensured.
[Pg 48]
Treatment of uncomplicated P.falciparum malaria in
special populations
Several important patient sub-populations, including young
children, pregnant women and patients taking potent enzyme inducers (e.g.
rifampicin, efavirenz), have altered pharmacokinetics, resulting in sub-optimal
exposure to antimalarial drugs. This increases the rate of treatment failure
with current dosage regimens. The rates of treatment failure are substantially
higher in hyperparasitaemic patients and patients in areas with artemisinin-resistant
falciparum malaria, and these groups require greater exposure to antimalarial
drugs (longer duration of therapeutic concentrations) than is achieved with
current ACT dosage recommendations. It is often uncertain how best to achieve this.
Options include increasing individual doses, changing the frequency or duration
of dosing, or adding an additional antimalarial drug. Increasing individual
doses may not, however, achieve the desired exposure (e.g. lumefantrine
absorption becomes saturated), or the dose may be toxic due to transiently high
plasma concentrations (piperaquine, mefloquine, amodiaquine, pyronaridine). An
additional advantage of lengthening the duration of treatment (by giving a
5-day regimen) is that it provides additional exposure of the asexual cycle to
the artemisinin component as well as augmenting exposure to the partner drug.
The acceptability, tolerability, safety and effectiveness of augmented ACT
regimens in these special circumstances should be evaluated urgently.
[Pg 56]
Treatment of uncomplicated P.falciparum malaria in
special populations
5.5 | PATIENTS CO-INFECTED WITH TUBERCULOSIS
Rifamycins, in particular rifampicin, are potent CYP3A4
inducers with weak antimalarial activity. Concomitant administration of
rifampicin during quinine treatment of adults with malaria was associated with
a significant decrease in exposure to quinine and a five-fold higher
recrudescence rate. Similarly, concomitant rifampicin with mefloquine in
healthy adults was associated with a there-fold decrease in exposure to
mefloquine.
In adults co-infected with HIV and tuberculosis who were
being treated with rifampicin, administration of artemether + lumefantrine
resulted in significantly lower exposure to artemether, dihydroartemisinin and
lumefantrine (nine-, six- and there-fold decreases, respectively).
There is
insufficient evidence at this time to change the current mg/kg bw dosing
recommendations; however, as these patients are at higher risk of recrudescent infections
they should be monitored closely.
[Pg 274-275]
Ref: WHO Guidelines for the Treatment of Malaria – 3rd Edition, 2015
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.