A traveler, returning from a stay of twenty days in an area at risk of malaria from chloroquine-resistant Plasmodium falciparum, continues to take atovaquone + proguanil (Malarone) as required, even for a week. A few days later asking for our opinion on a problem: he has just done a pregnancy test, which is positive. The woman recalls the recommendation not to become pregnant during treatment with Malarone and asks us what the risks are.
How to proceed?
The technical details of the drug and the various guidelines on malaria prophylaxis consider pregnancy a contraindication to treatment with Malarone, due to lack of data on it.
The question is no experience of administration of the combination atovaquone-proguanil in pregnancy?
perform a Medline search through and find some clinical trials in which the drug was administered for the treatment of malaria rather than prophylaxis.
We find three trials conducted by the same research group (1-3). Warning: reading the three studies is not clear whether the same patients appear in more than one trial. The one with the highest number of enrolled patients comparing 39 pregnant women (2nd and 3rd trimester) treated with artesunate-atovaquone-proguanil vs.. 42 treated with quinine; not been detected differences in the following parameters: birth weight, gestation length, birth defects, growth parameters and development of children monitored for a year (1).
Other two trials come to similar conclusions (2.3).
Finally, there is a pharmacokinetic and pharmacodynamic study of 26 women in the third trimester of pregnancy with malaria and treated with atovaquone-proguanil without severe adverse events or premature birth or miscarriage (4 ).
What can you conclude?
available studies were conducted on a limited population of pregnant women suffering from malaria, so these studies are not of sufficient magnitude to make a risk assessment. The doses of atovaquone-proguanil were, naturally, much higher than those for the chemoprophylaxis of malaria. It was not revealed an increased risk, but we must emphasize that the patients were in second and third in the first quarter instead. In any case, exposure Accident Malarone in pregnancy is not a sufficient reason for deciding whether to break the same. This is also the position of the UK National Travel Health Network and Centre (NaTHNaC), see:
Bibliography
(1) McGready R, Ashley EA, Moo E, Cho T, Barends M, Hutagalung R, Looareesuwan S, White NJ, Nosten F . A randomized comparison of artesunate-atovaquone-proguanil versus quinine in treatment for uncomplicated falciparum malaria during pregnancy. J Infect Dis 2005;192:846-53.
DOI: 10.1086/432551
(2) McGready R, Keo NK, Villegas L, White NJ, Looareesuwan S, Nosten F.
Artesunate-atovaquone-proguanil rescue treatment of multidrug-resistant Plasmodium falciparum malaria in pregnancy: a preliminary report.
Trans R Soc Trop Med Hyg 2003;97(5):592-4
DOI:10.1016/S0035-9203(03)80040-8
(3) McGready R, Stepniewska K, Edstein MD, Cho T, Gilveray G, Looareesuwan S, White NJ, Nosten F. The pharmacokinetics of atovaquone and proguanil in pregnant women with acute falciparum malaria.
Eur J Clin Pharmacol 2003;59:545-52.
DOI: 10.1007/s00228-003-0652-9
(4) Na-Bangchang K, Manyando C, Ruengweerayut R, Kioy D, Mulenga M, Miller GB, Konsil J. The pharmacokinetics and pharmacodynamics of atovaquone and proguanil for the treatment of uncomplicated falciparum malaria in third-trimester pregnant women.
Eur J Clin Pharmacol 2005; 61:573-82.
DOI: 10.1007/s00228-005-0969-7
0 comments:
Post a Comment