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close this bookGuidelines for the Treatment of Malaria (WHO; 2006; 266 pages) View the PDF document
View the documentGlossary
View the documentAbbreviations
open this folder and view contents1. Introduction
View the document2. The clinical disease
open this folder and view contents3. Treatment objectives
open this folder and view contents4. Diagnosis of malaria
open this folder and view contents5. Resistance to antimalarial medicines9
open this folder and view contents6. Antimalarial treatment policy
open this folder and view contents7. Treatment of uncomplicated P. Falciparum malaria10
close this folder8. Treatment of severe falciparum malaria14
View the document8.1 Definition
View the document8.2 Treatment objectives
View the document8.3 Clinical assessment
View the document8.4 Specific antimalarial treatment
View the document8.5 Practical aspects of treatment
View the document8.6 Follow-on treatment
View the document8.7 Pre-referral treatment options16
View the document8.8 Adjunctive treatment
View the document8.9 Continuing supportive care
View the document8.10 Additional aspects of clinical management
View the document8.11 Treatment during pregnancy
View the document8.12 Management in epidemic situations
View the document8.13 Hyperparasitaemia18
open this folder and view contents9. Treatment of malaria caused by P. vivax, P. ovale or P. malariae19
View the document10. Mixed malaria infections
open this folder and view contents11. Complex emergencies and epidemics
open this folder and view contentsAnnexes

8.5 Practical aspects of treatment

8.5.1 Artemisinins

Artemisinin is formulated as a suppository for rectal administration. Artemether and artemotil are formulated in oil and are given by intramuscular injection. They are both absorbed erratically, particularly in very severely ill patients. Artesunate is soluble in water and can be given either by intravenous or intramuscular injection. There are also rectal formulations of artesunate, artemether and dihydroartemisinin.

The dosing of artemisinin derivatives has been largely empirical. The doses recommended here are those that have been most widely studied. The only recent change is the higher maintenance dose of parenteral artesunate recommended (2.4 mg/kg bw), which is based on pharmacokinetic and pharmacodynamic studies and by extrapolation from studies with oral artesunate. Expert opinion is that the previously recommended maintenance dose of 1.2 mg/kg bw may have been insufficient in some patients.

Artesunate is dispensed as a powder of artesunic acid. This is dissolved in sodium bicarbonate (5%) to form sodium artesunate. The solution is then diluted in approximately 5 ml of 5% dextrose and given by intravenous injection or by intramuscular injection to the anterior thigh. The solution should be prepared freshly for each administration and should not be stored.

Artemether and artemotil are dispensed dissolved in oil (groundnut, sesame seed) and given by i.m. injection into the anterior thigh.

8.5.2 Quinine

Whereas many antimalarials are prescribed in terms of base, for historical reasons quinine doses are often recommended in terms of salt (usually sulfate for oral use and dihydrochloride for parenteral use). Recommendations for doses of this and other antimalarials should state clearly whether the salt or base is being referred to (doses with different salts must have the same base equivalents). Quinine must never be given by intravenous injection, as lethal hypotension may result. Quinine dihydrochloride should be given by rate-controlled infusion in saline or dextrose solutions at a rate not exceeding 5 mg salt/kg bw per hour. If this is not possible then it should be given by intramuscular injection to the anterior thigh, not the buttock (to avoid sciatic nerve injury). The first dose should be split, 10 mg/kg bw to 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 either formulated or diluted to concentrations 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 dose (loading dose) is the most important in the treatment of severe malaria, this 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 from excessive treatment initially. After the second day of parenteral treatment, if there is no clinical improvement or in acute renal failure, the maintenance doses of quinine given by infusion should be reduced by one-third to avoid accumulation.

8.5.3 Adjustment of dosing in renal failure or hepatic dysfunction

The dosage of artemisinin derivatives does not need adjustment in vital organ dysfunction. Quinine (and quinidine) levels may accumulate in severe vital organ dysfunction. If there is no clinical improvement or the patient remains in acute renal failure the dose should be reduced by one-third after 48 h. Dosage adjustments are not necessary if patients are receiving either haemodialysis or haemofiltration. Dosage adjustment by one-third is necessary in patients with hepatic dysfunction.

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