| Artesunate (Malacef®) | Quinine (Quinimax®) | |
| Loading dose | 2.4 mg∙kg−1 intravenously at H0, H12 and H24 Gently dilute 60 mg of artesunate in 1 ml of sodium bicarbonate provided, then dilute again in 5 ml of 5% glucose, to obtain 6 ml of a 10 mg solution ml−1 Injection rate: 3 ml∙min−1 | 16 to 20 mg∙kg−1 over 4 hours intravenously in G10%, without exceeding 1800 mg (if obese patient) Contraindications to the loading dose: - QT prolongation > 25% - Previous treatment with quinine, halofantrine or mefloquine Dysfunction hepatic: reduction of one third of the loading dose |
| Maintenance dose | 2.4 mg∙kg−1 24 h−1 for a maximum of 7 days then systematic relay with a complete 3-day treatment with ACT (oral route or SNG) After a minimum of 3 to 4 intravenous doses, if the patient is conscious, without criteria persistent in severity, with functional transit: oral relay with a complete 3-day treatment with ACT (Eurartesim® or Riamet®) | To start 4 hours after the end of the loading dose: - Either 24 to 30 mg∙kg−1∙d−1 continuously intravenously - Or 8 to 10 mg∙kg−1 over 4 hours every 8 hours, without exceeding 3000 mg∙d−1 (obese) Relay per os at the same dosage to be considered after 72 hours if functional digestive tract Total duration: 7 days |
| Specific monitoring | Clinical and blood examination on D3, D7, D14, D21 and D28: particularly NFS, reticulocyte level, haptoglobin (PADH) level Smear/thick drop on D3, D7, D28 If onset of anemia delayed until D28 (PADH): complete diagnostic work-up for anemia Daily ECG | Hourly blood glucose during the loading dose then every 4 hours. Increased risk of hypoglycaemia in pregnant women Quininemia at the end of the loading dose then daily, especially if renal or hepatic insufficiency Expected concentration between 10 and 15 mg∙l−1 after loading dose, then between 10 and 12 mg∙l−1. Check-up recommended at the 72nd hour Daily ECG with QTc Smear/thick film check-up on D3, D7, D28 |
| Side effects | Digestive disorders Neutropenia (1%), reticulocytopenia (<1%) Alteration in liver function angioedema (1/3000) Theoretical risk of neurological damage, but not found clinically Risk of transient deafness Possible risk of convulsion and vertigo Delayed hemolytic anemia (PADH) | Sometimes very profound hypoglycaemia with coma Prolongation of QTc followed by arrhythmias and conduction disorders Cinchonism (damage to the VIIIth cranial nerve: digestive disorders, headaches, tinnitus, reversible deafness). This phenomenon reflects the therapeutic impregnation, it should not lead to a reduction in dosage, and disappears when stopped |
| Pharmacokinetics (PK)/ Pharmacodynamics (PD) | Prodrug hydrolysed in the systemic circulation to dihydroartemisinin (DHA) Cmax reached in 1 hour Bioavailability: 80% Protein binding: 75% Hepatic elimination Elimination half-life: 15 to 45 min In the event of severe renal impairment: no dosage modifications | Cmax reached in 1 to 3 hours Bioavailability: 76% Binding to plasma proteins in a concentration-dependent manner Hepatic elimination Elimination half-life: 12 hours In the event of severe renal impairment: decrease in dosage after the first 48 hours by adapting to quinine levels |