Riamet & Rifampicin Co-administration

 [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