What are the contraindications for Artesunate?

Contraindications for Artesunate

The main contraindications for artesunate include hypersensitivity reactions, risk of QT prolongation, and pregnancy in certain circumstances. 1, 2

Primary Contraindications

• Hypersensitivity reactions: Severe allergic reactions to artesunate, though rare, are an absolute contraindication to its use 2
• QT prolongation risk: For patients with significant risk of QT interval prolongation, artesunate should be used with caution or avoided 1
• Specific geographic considerations: For patients from Southeast Asia (especially the Greater Mekong sub-region) with high levels of resistance to artemisinin-based combination therapies (ACTs), alternative treatments should be considered 1

Special Populations

Pregnancy

• Artesunate can be used in all trimesters of pregnancy for severe malaria, as the benefits outweigh potential risks 1
• For uncomplicated malaria in pregnancy, artemether-lumefantrine is now endorsed by WHO and CDC for use in all trimesters 1

G6PD Deficiency

• While artesunate itself is not contraindicated in G6PD deficiency, caution should be exercised due to the risk of post-artesunate delayed hemolysis (PADH) 1, 3
• Monitoring for hemolysis (hemoglobin, haptoglobin, and lactate dehydrogenase levels) at days 7,14,21, and 28 is recommended in these patients 1, 3

Adverse Effects to Monitor

• Post-artesunate delayed hemolysis (PADH): A significant adverse event that occurs in approximately 37.4% of patients treated with artesunate 1, 3
• Common mild adverse effects: Nausea, vomiting, anorexia, and dizziness 4
• Less common but serious effects: Neutropenia, anemia, hemolysis, elevated liver enzymes 2, 5

Clinical Considerations

• For patients with uncomplicated malaria where artesunate is contraindicated, alternative treatments include:

  • Atovaquone-proguanil 1
  • Quinine sulfate with doxycycline or clindamycin 1
  • Mefloquine (where appropriate) 1

• For severe malaria requiring parenteral treatment where artesunate is contraindicated:

  • Intravenous quinine is the recommended alternative, administered at 20 mg salt/kg over 4 hours (loading dose) followed by 10 mg/kg over 4 hours starting 8 hours after initiation of treatment and then every 8 hours 1, 3
  • Monitor for quinine-specific adverse effects including cinchonism (tinnitus, vertigo, headache), hypoglycemia, and QT prolongation 1

Monitoring Recommendations

• For patients receiving artesunate for severe malaria, monitor parasitemia every 12 hours until decline to <1%, then every 24 hours until negative 1, 3
• Continuous monitoring of cardiocirculatory, pulmonary, renal, and metabolic parameters is essential for patients with severe malaria 1
• Laboratory monitoring should include complete blood counts, liver function tests, and parameters for hemolysis 3, 5

Practical Management of Contraindications

• In cases of known hypersensitivity to artesunate, quinine-based regimens should be used as alternative first-line therapy 1, 6
• For patients at risk of QT prolongation requiring treatment for severe malaria, careful cardiac monitoring should be implemented if artesunate must be used 1
• When treating patients from regions with known artemisinin resistance, consider combination therapy or alternative agents 1