Can anaphylactic reactions occur with intravenous (IV) artesunate (artemisinin derivative)?

From the Guidelines

Yes, anaphylactic reactions can occur with intravenous (IV) artesunate, though they are rare. IV artesunate, a water-soluble artemisinin derivative used for severe malaria treatment, has been associated with hypersensitivity reactions including anaphylaxis in a small percentage of patients 1. Healthcare providers should monitor patients closely during and after administration, particularly within the first few minutes to hours. Symptoms of anaphylaxis may include urticaria, angioedema, bronchospasm, hypotension, and cardiovascular collapse. Emergency medications and equipment should be readily available when administering IV artesunate. The mechanism behind these reactions is thought to be related to immediate hypersensitivity, possibly IgE-mediated. The standard adult dose of IV artesunate is 2.4 mg/kg at 0,12,24, and 48 hours, but treatment should be immediately discontinued if anaphylaxis occurs, and appropriate emergency treatment initiated, following the guidelines for anaphylaxis management, which include the administration of epinephrine, antihistamines, and glucocorticoids as adjunctive therapy 1. Some key points to consider in the management of anaphylaxis include:

• Administering epinephrine promptly, as it is the first-line treatment for anaphylaxis
• Using antihistamines and glucocorticoids as adjunctive therapy, but not as a replacement for epinephrine
• Monitoring patients closely for signs of anaphylaxis, such as hypotension, bronchospasm, and cardiovascular collapse
• Being prepared to provide emergency care, including oxygen therapy, fluid replacement, and vasopressor support, as needed. Patients with a history of allergic reactions to artemisinin compounds should not receive artesunate, and alternative antimalarial treatments should be considered. It is essential to follow the most recent guidelines for anaphylaxis management, as outlined in the 2020 practice parameter update 1, to ensure the best possible outcomes for patients.

From the Research

Anaphylactic Reactions with Intravenous Artesunate

• Anaphylactic reactions to artesunate, an artemisinin derivative, are rare entities 2
• Common adverse reactions to artemisinin derivatives include nausea, vomiting, anorexia, and dizziness, while more serious but less-frequent toxic effects include neutropenia, anemia, hemolysis, elevated liver enzymes, and severe allergic reactions 2
• A case report has been documented where a patient experienced anaphylaxis to parenteral artesunate, which was successfully managed 2

Anti-Allergic Effects of Artesunate

• Artesunate has been shown to possess anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders 3
• The anti-allergic effects of artesunate were evaluated in animal models of IgE-dependent anaphylaxis, and the results suggest that artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner 3

Management of Anaphylaxis

• Epinephrine is the first-line treatment for anaphylaxis, and delayed epinephrine administration is a risk factor for fatal anaphylaxis 4
• The use of antihistamines and corticosteroids in anaphylaxis management is not well established, and convincing data on their role are sparse 4
• A study found that patients treated with prehospital epinephrine were less likely to have uncontrolled reactions, receive intravenous fluids in the emergency department, and be admitted after the reaction 4
• Another study suggested that prompt epinephrine treatment is crucial, and the use of antihistamines in conjunction with epinephrine may reduce the risk of uncontrolled reactions 5