TOLERABILITY OF PROPHYLACTIC LARIAM(R) REGIMENS

Three hundred and fifty-nine US Marines participated in a randomized d ouble-blind clinical trial to assess tolerance of two prophylactic mef loquine regimens [250 mg salt weekly (n = 157) or 250 mg daily for 3 d ays followed by 250 mg weekly (n = 46)] compared with 300 mg weekly ch loroquine (n = 156) over a 12-week period. The study participants were seen daily for four days, then weekly for 11 weeks. On each visit, th e subject answered two computerized questionnaires (a review of body s ystems and an evaluation of mood states), participated in a physician interview, and was administered medications under supervision. A rando m sample of each group was assigned to either pharmacokinetic sampling or to wear a wrist watch size computerized sleep monitor (actigraph). The frequencies of intercurrent illness and other concomitant medicat ions were tabulated. End study mefloquine plasma levels were obtained on all study participants. The results obtained showed no compromise i n function due to dizziness or incoordination in the mefloquine groups . Overall, both weekly mefloquine and loading dose mefloquine were wel l tolerated. Sleep disturbance and increased dream activity were detec ted in the mefloquine groups. Depressive feelings were noted in two to three times more individuals in the mefloquine groups than in the chl oroquine group early in the course of the study, and resolved in the m ajority of subjects as tolerance developed. Steady state mefloquine pl asma levels were attained rapidly with the loading dose regimen in fou r days versus seven weeks with weekly mefloquine. The mefloquine loadi ng dose regimen should be considered as an option for short-term adult travelers or military personnel to chloroquine-resistant areas of the world.