Practical info Artemether Artemether is two to three times less active than its main metabolite dihydroartemisinin. Artemether can be given as an oilbased intramuscular injection or orally. In severe falciparum malaria, the concentration of the parent compound predominates after intramuscular injection, whereas parenteral artesunate is hydrolysed rapidly and almost completely to dihydroartemisinin. Given intramuscularly, artemether may be absorbed more slowly and more erratically than water-soluble artesunate, which is absorbed rapidly and reliably after intramuscular injection. These pharmacological advantages may explain the clinical superiority of parenteral artesunate over artemether in severe malaria. Artemether is dispensed dissolved in oil (groundnut, sesame seed) and given by intramuscular injection into the anterior thigh. Therapeutic dose: The initial dose of artemether is 3.2 mg/kg bw intramuscularly (to the anterior thigh). The maintenance dose is 1.6 mg/kg bw intramuscularly daily. Quinine Quinine treatment for severe malaria was established before the methods for modern clinical trials were developed. Several salts of quinine have been formulated for parenteral use, but the dihydrochloride is the most widely used. The peak concentrations after intramuscular quinine in severe malaria are similar to those after intravenous infusion. Studies of pharmacokinetics show that a loading dose of quinine (20 mg salt/kg bw, twice the maintenance dose) provides therapeutic plasma concentrations within 4 h. The maintenance dose of quinine (10 mg salt/ kg bw) is administered at 8-h intervals, starting 8 h after the first dose. If there is no improvement in the patient’s condition within 48 h, the dose should be reduced by one third, i.e. to 10 mg salt/kg bw every 12 h. Rapid intravenous administration of quinine is dangerous. Each dose of parenteral quinine must be administered as a slow, rate-controlled infusion (usually diluted in 5% dextrose and infused over 4 h). The infusion rate should not exceed 5 mg salt/kg bw per h. Whereas many antimalarial drugs are prescribed in terms of base, for historical reasons quinine doses are usually recommended in terms of salt (usually sulphate for oral use and dihydrochloride for parenteral use). Recommendations for the doses of this and other antimalarial agents should state clearly whether the salt or the base is being referred to; doses with different salts must have the same base equivalents. Quinine must never be given by intravenous bolus injection, as lethal hypotension may result. Quinine dihydrochloride should be given by rate-controlled infusion in saline or dextrose solution. If this is not possible, it should be given by intramuscular injection to the anterior thigh; quinine should not be injected into the buttock in order to avoid sciatic nerve injury. The first dose should be split, with 10 mg/kg bw into each thigh. Undiluted quinine dihydrochloride at a concentration of 300 mg/ mL is acidic (pH 2) and painful when given by intramuscular injection, so it is best to administer it either in a buffered formulation or diluted to a concentration of 60–100 mg/mL for intramuscular injection. Gluconate salts are less acidic and better tolerated than the dihydrochloride salt when given by the intramuscular and rectal routes. As the first (loading) dose is the most important in the treatment of severe malaria, it should be reduced only if there is clear evidence of adequate pre-treatment before presentation. Although quinine can cause hypotension if administered rapidly, and overdose is associated with blindness and deafness, these adverse effects are rare in the treatment of severe malaria. The dangers of insufficient treatment (i.e. death from malaria) exceed those of excessive initial treatment.