What is the interaction between artemether (antimalarial drug)/lumefantrine (antimalarial drug) and promethazine (antihistamine)?

From the Guidelines

Promethazine should be used with caution when taking artemether/lumefantrine due to potential interactions that could increase the risk of heart rhythm problems. Both medications can prolong the QT interval on an electrocardiogram, and using them together may enhance this effect, potentially leading to dangerous heart arrhythmias 1. Additionally, promethazine may inhibit certain liver enzymes that metabolize artemether/lumefantrine, potentially increasing blood levels of the antimalarial drugs and their side effects. If both medications are necessary, healthcare providers should monitor the patient closely, possibly with ECG monitoring, especially in patients with existing heart conditions, electrolyte abnormalities, or those taking other QT-prolonging medications. Some key points to consider when managing patients with malaria in non-endemic settings include:

• The use of artemether/lumefantrine as a first-line treatment for uncomplicated P. falciparum malaria, with a recommended dose of 4 tablets (20 mg artemether and 120 mg lumefantrine) per day for 3 days 1.
• The potential for promethazine to interact with artemether/lumefantrine, leading to increased risk of QT interval prolongation and cardiac arrhythmias 1.
• The importance of monitoring patients closely for signs of cardiac toxicity, particularly those with pre-existing heart conditions or taking other QT-prolonging medications 1. Alternative antihistamines that don't affect heart rhythm, such as loratadine or cetirizine, might be safer options for patients requiring antimalarial therapy with artemether/lumefantrine. This interaction occurs because both medications affect cardiac electrical conduction through different mechanisms, and promethazine's effect on cytochrome P450 enzymes can alter the metabolism of artemether and lumefantrine.

From the Research

Interaction between Artemether/Lumefantrine and Promethazine

There are no direct studies on the interaction between artemether/lumefantrine and promethazine. However, we can look at the pharmacokinetics of artemether and lumefantrine to understand potential interactions:

• Artemether and lumefantrine are metabolized by cytochrome P450 isoenzyme CYP3A4 2, 3.
• The absorption of lumefantrine is poor during the fasting state, but it becomes adequate with a normal diet 4, 5.
• The pharmacokinetics of artemether and lumefantrine can be affected by other drugs that inhibit or induce CYP3A4 2, 3.

Potential Interaction with Promethazine

• Promethazine is an antihistamine that can have various drug interactions, but its specific interaction with artemether/lumefantrine is not well-studied.
• Since promethazine is not a known inhibitor or inducer of CYP3A4, it is unlikely to have a significant interaction with artemether/lumefantrine based on the available information 2, 3.
• However, without direct studies, it is difficult to confirm the absence of any interaction, and caution should be exercised when co-administering these drugs.

Pharmacokinetics of Artemether and Lumefantrine

• The pharmacokinetics of artemether and lumefantrine have been studied in various populations, including adults and children 5, 6.
• The absorption, distribution, metabolism, and elimination of these drugs can vary depending on factors such as age, diet, and co-administration with other drugs 4, 5, 6.
• Understanding the pharmacokinetics of artemether and lumefantrine is essential to optimize their use and minimize potential interactions with other drugs.