Administration of Artesunate After Artemether in Malaria Treatment
Intravenous artesunate can be administered after 12 hours of intramuscular artemether in the treatment of malaria, as both are artemisinin derivatives used for severe malaria with different pharmacokinetic profiles but similar mechanisms of action.
Rationale for Sequential Administration
- Intravenous artesunate is the first-line treatment for severe malaria due to its faster parasite clearance and shorter ICU stays compared to other antimalarials 1.
- When transitioning between artemisinin derivatives, there is no contraindication to administering artesunate after artemether, as both work through the same mechanism of parasite clearance 2.
- Artesunate provides more rapid parasite clearance than artemether, with studies showing significantly earlier mean parasite clearance times (PCT50: 9.1 versus 13.8 hours) 3.
Treatment Protocol for Severe Malaria
- For severe malaria, intravenous artesunate should be administered at 2.4 mg/kg body weight at 0,12, and 24 hours, and then daily until oral medication can be taken 2.
- If injectable artesunate is unavailable, intramuscular artemether can be used at 3.2 mg/kg on admission followed by 1.6 mg/kg daily 2.
- When switching from artemether to artesunate, the standard artesunate dosing schedule can be followed, with timing adjusted based on the last artemether dose 1.
Clinical Considerations
- Both artemether and artesunate share dihydroartemisinin as their common active metabolite, but artesunate achieves higher initial plasma concentrations, which explains its faster clinical effect 3.
- Monitoring of peripheral blood parasitemia should be done every 12 hours after starting treatment until a decline to <1% is observed, then every 24 hours until negative results 2.
- For patients treated with IV artesunate, monitoring for post-artesunate delayed hemolysis (PADH) at days 7,14,21, and 28 is warranted 2, 1.
Completion of Treatment
- After parenteral therapy with either artemether or artesunate, patients should be switched to a complete course of oral artemisinin-based combination therapy (ACT) once they are clinically improved and able to take oral medication 2, 1.
- The full course of the chosen ACT should be administered to prevent recrudescence, which can occur with short courses of artemisinin derivatives 4.
Important Considerations and Cautions
- Both artesunate and artemether are well-tolerated in adults and children with no evidence of serious clinical toxicity 5.
- When using artemisinin derivatives sequentially, the total cumulative dose should be considered to avoid potential toxicity, though both drugs have excellent safety profiles 6.
- In areas with known or suspected artemisinin resistance, combination therapy with a partner drug is essential to prevent the development of resistance 4.