Is it safe to use artemether (antimalarial) lumefantrine (antimalarial) with azithromycin (antibiotic) for treating uncomplicated malaria with potential bacterial co-infection?

From the Guidelines

Artemether-lumefantrine can be used with azithromycin for treating uncomplicated malaria with suspected bacterial co-infection, but caution is advised due to potential cardiac risks. The standard artemether-lumefantrine regimen (six doses over three days) can be administered alongside appropriate azithromycin dosing (typically 500mg daily for 3-5 days for most bacterial infections) 1. However, this combination requires careful consideration of potential cardiac risks, as both medications can prolong the QT interval, potentially causing dangerous heart rhythm disturbances, especially in patients with pre-existing heart conditions, electrolyte abnormalities, or those taking other QT-prolonging medications 1.

Key Considerations

• Patients with risk factors may need ECG monitoring during treatment.
• Both medications may be metabolized through similar liver pathways, potentially affecting drug levels.
• This combination is often necessary in clinical practice when bacterial co-infection is suspected alongside malaria, as untreated bacterial infections can worsen outcomes.
• If this combination is used, patients should be monitored for side effects including irregular heartbeat, dizziness, or fainting, which could indicate cardiac complications requiring immediate medical attention.

Treatment Recommendations

• Azithromycin is generally well tolerated with minimal side effects, usually dose-related gastrointestinal complaints 1.
• The efficacy of single dose regimens for both FQs and azithromycin supports their acceptability (Strong recommendation, high level of evidence) 1.
• Azithromycin should be considered the first-line agent in cases of dysentery (Strong recommendation, high level of evidence) as well as acute watery diarrhea with greater than mild fever given the increased likelihood of FQ-resistant Campylobacter, and other bacterial causes such as Shigella spp., enteroinvasive E. coli, Aeromonas spp., Plesiomonas spp., and Yersinia enterocolitica 1.

Monitoring and Precautions

• Patients should be monitored for side effects including irregular heartbeat, dizziness, or fainting, which could indicate cardiac complications requiring immediate medical attention.
• ECG monitoring may be necessary for patients with risk factors.
• Consideration should be given to the potential for drug interactions in a given patient.

From the Research

Safety of Using Artemether Lumefantrine with Azithromycin

• The use of artemether lumefantrine with azithromycin for treating uncomplicated malaria with potential bacterial co-infection has been explored in various studies 2.
• A randomized, controlled trial in Tanzanian children found that azithromycin plus artesunate was less effective than artemether-lumefantrine for treating uncomplicated malaria, with a higher parasitological failure rate by day 28 2.
• However, there is no direct evidence on the safety of using artemether lumefantrine with azithromycin, as the studies focused on the efficacy of artemether-lumefantrine alone or in combination with other antimalarials 3, 4, 5.
• The pharmacokinetic and pharmacodynamic properties of lumefantrine have been investigated in young children and pregnant women, suggesting that revised dosing regimens may be necessary to improve drug exposure 6.

Potential Interactions and Side Effects

• The combination of artemether lumefantrine with azithromycin may increase the risk of adverse effects, such as gastrointestinal and neurological disorders, which are commonly reported with artemether lumefantrine 4, 5.
• Azithromycin may also interact with lumefantrine, potentially affecting its absorption or increasing the risk of QT interval prolongation 5.
• However, without direct evidence on the safety of this combination, it is difficult to predict the potential interactions and side effects.

Efficacy of Artemether Lumefantrine

• Artemether lumefantrine has been shown to be highly effective in treating uncomplicated malaria, with cure rates of >95% in many different patient populations 3.
• The combination has also been found to be effective in areas with high levels of resistance to other antimalarials 5.
• However, the efficacy of artemether lumefantrine may be affected by factors such as patient age, weight, and pregnancy status, as well as the presence of bacterial co-infections 2, 6.