Recommended Chemotherapeutic Regimens for Treating Severe Maaria

As formulations and preparations (e.g. base/salt/ compound) of antimalarial drugs vary from centre to centre, it is CRITICAL TO CHECK DOSES with local pharmacists, particularly for drugs used parenterally.

1. Parenteral quinine. A loading dose of parenteral quinine should be given to most patients to ensure rapid attainment of effective drug concentrations. A loading dose should NOT be given if the patient has received quinine, quinidine or mefloquine during the preceding 1224 hours.

• If intensive care facilities are available, 7 mg quinine dihydrochloride salt/kg diluted in 60 ml 0.9% saline should be infused by motor-driven syringe pump over 30 minutes, followed by an intravenous infusion of 10 mg/

kg quinine dihydrochloride diluted in 10 ml/ kg isotonic fluid, given over the next 4 hours (White, 1996b). Maintenance doses should be given 8 hourly, as indicated below.

• Alternatively, a loading dose of 20 mg salt/kg may be infused in 500 ml 5% glucose over 4 hours, followed by a maintenance infusion of 10 mg salt/kg over 2-8 hours, repeated every 8 hours until oral therapy is tolerated. The maintenance dose should be commenced 4 hours after the loading dose is completed (White, 1996b).

• If an intravenous infusion cannot be given, quinine dihydrochloride diluted to between 60 and 100mg/ml may be administered by deep intramuscular injection into the anterior aspect of the thigh. The initial loading dose can be divided and half injected into each leg. This regimen has been shown to be satisfactory for the treatment of severe malaria in children in Kenya (Pasvol et al., 1991).

Note: The bisulphate salt of quinidine has only 70% of the activity of the sulphate salt and appropriate dosage adjustments should be made.

2. Parenteral quinidine. Quinidine is more active than quinine but it is also more cardio-toxic. It is mainly used in areas where parenteral quinine is not commonly available (such as in the USA Miller et al., 1989). It has an approximately four-fold greater effect in prolonging the EKG QT interval than quinine and, although arrhythmias have not been reported in association with malaria therapy, EKG monitoring is required. A loading dose of quinidine gluconate (10 mg salt/ kg, max 600 mg) should be infused in normal saline over 1-2 hours followed by 0.02mg/kg/ min by infusion pump until the patient can swallow quinine tablets (White, 1996b). The infusion rate should be slowed if the plasma quinidine concentration exceeds 6 mg/ml, or the QT interval exceeds 25% of the baseline value.

Both quinine and quinidine may accumulate during renal failure, so doses should be decreased to one-third to one-half after 48 hours or serum levels should be measured (Murphy and Oldfield, 1996). The therapeutic range for the unbound drug probably lies between 0.8 and 2mg/l, depending on the sensitivity of the infecting malaria parasites. This corresponds to total plasma concentrations of 8-20 mg/1 for quinine and 4-8 mg/1 for quinidine.

• Treatment with quinine or quinidine should be combined with doxycycline (100 mg twice daily for seven days), commenced while the patient is in hospital, or pyrimethamine-sulphadoxine (3 tablets) given on the last day of quinine therapy, provided that these drugs are not contraindicated (in which circumstance a longer course of quinine would be required).

3. Chloroquine is as effective as quinine in the treatment of chloroquine-sensitive falciparum malaria.

• The total dose should be 25 mg base/kg/day (not exceeding 15 mg base/kg on the first day) administered as follows. An initial dose of 10 mg base/kg intravenously by constant rate infusion (or, if infusion pump unavailable, in 500 ml isotonic saline or 5% dextrose) given over 8 hours, followed by 15 mg base/kg over 24 hours (White, 1996b). Oral treatment should be substituted as soon as the patient can take tablets.

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