Post-marketing surveillance: adverse events during long-term use of atovaquone/proguanil for travelers to malaria-endemic countries.
BACKGROUND
Atovaquone/proguanil in Europe is only licensed for 4 weeks of travel. Data on its long-term tolerability in nonimmune travelers are scarce.


METHODS
We prospectively studied adverse reactions reported by long-term travelers using atovaquone/proguanil among a population intolerant to mefloquine. The average length of atovaquone/proguanil use was 9 weeks (4.5 to 34 weeks). Adverse events were recorded on a regular questionnaire. Travelers rated complaints as: (1) mild, not interfering with their daily activities; (2) moderate, causing interference, such as canceling a trip or being confined to the hotel; or (3) severe, causing a visit to a doctor or clinic. Hospital admission was classified as category 3 and specified. We then compared our data with those on adverse reactions from 2 large multicenter studies of atovaquone/proguanil in nonimmune travelers.


RESULTS
One hundred and fifty-four subjects used atovaquone/proguanil for a total of 1538 weeks. Diarrhea was the most common ailment (18%). Further complaints were abdominal pain (mild 4%, moderate 5%, severe 2%), headache (mild 4%, moderate 4%, severe 1%), dizziness (mild 3%, moderate 1%, severe 1%), and insomnia (mild 6%, moderate 0%, severe 0%). Two subjects of 154 (1%) discontinued prophylaxis, both due to diarrhea. Nobody was admitted to hospital. No case of malaria was reported. Comparison with data from previous, larger atovaquone/proguanil studies shows that the adverse events reported by the long-term atovaquone/proguanil users are no different in type and frequency of occurrence to those travel-related health problems normally encountered in the Tropics.


CONCLUSIONS
Atovaquone/proguanil was well tolerated by these long-term travelers. Long-term users of atovaquone/ proguanil antimalarial prophylaxis suffer no more ailments than normally occur to travelers in tropical regions.
Overbosch
David
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Travel Clinic, Harbor Hospital, Rotterdam, The Netherlands.
D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D053626:Atovaquone; D004338:Drug Combinations; D019353:Endemic Diseases; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008288:Malaria / Q000453:epidemiology / Q000517:prevention & control*; D008297:Male; D009285:Naphthoquinones / Q000008:administration & dosage / Q000009:adverse effects*; D011358:Product Surveillance, Postmarketing; D002727:Proguanil / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D014195:Travel
D000962:Antimalarials; D004338:Drug Combinations; D009285:Naphthoquinones; C109496:atovaquone, proguanil drug combination; D002727:Proguanil; D053626:Atovaquone