MEFLOQUINE TREATMENT OF ACUTE FALCIPARUM-MALARIA - A PROSPECTIVE-STUDY OF NON-SERIOUS ADVERSE-EFFECTS IN 3673 PATIENTS

Between 1990 and 1994, a series of prospective studies were conducted to optimize the treatment of multidrug-resistant falciparum malaria on the borders of Thailand. The tolerance of various treatment regimens containing either mefloquine 15 mg/kg (M15) or 25 mg/kg (M25) was eval uated in 3673 patients aged between 6 months and 88 years. Early vomit ing (within 1 hour) is an important determinant of treatment outcome i n these areas, despite re-administration of the dose. Overall, 7% of t he patients vomited within an hour. Significant risk factors were age less than or equal to 6 years (relative risk (RR), 3.9) or >50 years ( RR, 2.7), the higher mefloquine dose (M25) (RR, 2.7), vomiting <24 hou rs before enrolment (RR, 2.5), axillary temperature >38.0 degrees C (R R, 1.6), and parasitaemia >10 000/mu l (RR, 1.3). in children less tha n or equal to 2 years, 30% vomited with M25, and 13% did not tolerate a repeat dose. Vomiting was reduced 40% by splitting the higher dose ( RR, 0.6; 95% Cl, 0.4-0.8), and 50% by giving mefloquine on the second day in combination with artesunate (RR, 0.5; Cl, 0.3-0.9). Anorexia, n ausea, vomiting, dizziness, and sleeping disorders were 1.1-1.4 times more frequent with M25 than M15 in the three days following treatment, but were similar in the single or split-dose M25 groups, despite twof old higher mefloquine concentrations obtained with the latter. There w as no evidence that diarrhoea, headache, and abdominal pain were assoc iated with mefloquine use. High-dose mefloquine is well tolerated but should be given as a split dose.