Close

      This website requires cookies. Please accept or refuse these cookies first.
      For more info about our cookies, please read our cookies policy.

      Wanda, homepage
      Make an appointment
      Wanda for travellers

      Malaria tablets: atovaquone-proguanil

      Latest update: - Authors: Nele Alders, Ula Maniewski

      Atovaquone-proguanil (Malarone®)

      Prevention of malaria caused by Plasmodium falciparum.

      Formulation

      • adult tablet: 250mg atovaquone and 100mg proguanil
      • junior tablet: 62.5mg atovaquone and 25mg proguanil
      • a tablet cutter can be used to cut the tablets into quarter or the pharmacist can prepare a special formulation
      • no liquid formulation available

      Half- Life

      • atovaquone: 2-3 days
      • proguanil: 12-25 hours

      Dosing schedule

      • adults and children >40kg: 1 adult tablet per day
      • children >5kg: can be used in adjusted dose based on the weight
      • duration: daily, to start 1-2 days before entering risk zone until 7 days after leaving endemic area

      Administration

      • take tablet with a fatty meal or milk to enhance absorption
      • tablets may be crushed and mixed with a small amount of something sweet (e.g., condensed milk, chocolate syrup, chocolate spread) to mask the bitter taste
      • in case of vomiting within the hour of administration, a repeat dose is advised

      Protection

      • more than 95% protection against P. falciparum.
      • available data indicate protection against primary attacks of P. vivax
      • no protectection against hypnozoite-induced episodes of P. vivax or P. ovale

      Contra- indications

      • do not administer in case of severe kidney insufficiency (creatinine clearance <30ml/min).
      • hypersensitivity to atovaquone-proguanil
      • depression and epilepsy are not contra-indications
      • it can be used in those known to be G6PD-deficient

      Precautions

      • It may enhance the anticoagulant effect of warfarin or other coumarin- anticoagulation (increased risk of bleeding risk). Monitoring the anticoagulant response (INR and signs of bleeding), closely following the addition or cessation of atovaquone-proguanil, is advised.
      •  It should not be taken together with Vivotif ® (oral live attenuated typhoid fever vaccine) since it can diminish the efficacy of the vaccine. Preferably, an interval of 7 days with a minimum of 3 days is respected.
      • Plasma concentrations of atovaquone are reduced by rifabutin and rifampicin, most nonnucleoside reverse transcriptase inhibitors, boosted protease inhibitors of HIV, tetracycline and metoclopramide which may lead to possible therapeutic failure of atovaquone so preferably avoid concomitant use.
      • Atovaquone interacts with some antiretroviral drugs. For up-to-date information and interactions use the HIV Drug Interactions website.

      Breastfeeding

      • It can be used during breastfeeding if the child is >5kg. The amount of medication in breast milk will not protect the infant from malaria. Therefore, the breastfeeding child needs his or her own prophylaxis. 

      Pregnancy

      • Malaria infection poses a significant risk in pregnancy,  yet data on safety of prophylaxis in pregnancy are sparse. The current advice is that atovaquone- proguanil should only be used if there is no suitable alternative available.

      Different sources offer varying recommendations. According to the medication leaflet it can be used during pregnancy if there is a clear risk-benefit, this is in line with the advice of the CDC. The WHO claims that there are insufficient data, and therefore it is not recommended.
      The guideline in the United Kingdom  does not recommend the use during pregnancy due to sparse data but states that it can be considered in the second or third pregnancy if there are no other appropriate options. The French guideline states that it can be used during pregnancy.   
      The studies performed during pregnancy are limited and retrospective. Animal studies showed no evidence for teratogenicity. A retrospective analyses looked at pregnancies and live births among active duty military woman in the United states. Among 198 164 pregnancies 50 were exposed to atovaquone-proguanil. They found a non-statistically significant increase in the risk of fetal loss. Overall 28% of exposed pregnancies ended in fetal loss, compared to 17.6% in unexposed pregnancies. However this is a small number of exposed pregnancies, the mothers in the exposed group were older and more of them (94%) were in the first trimester compared to the control groups ( 85% and 74%).
      A systemic review of the safety of atovaquone-proguanil for malaria prevention and treatment in pregnancy suggested that, although only limited data available, outcomes following exposure during pregnancy are similar to expected rates in similar populations. A registry-based cohort study of the inadvertent use of atovaquone-proguanil in weeks 3 to 8 after conception identified 149 pregnancies and found no significant association between exposure to atovaquone-proguanil in early pregnancy and the risk of a major birth defect.


      Side effects

      • The most frequent side effects are headaches and gastro-intestinal upsets.


      Advantages and disadvantages

      Advantages
      Disadvantages
      well tolerated expensive, especially for longer duration
      good for last-minute travellers
      paediatric tablets available

      Additional information

      References

      Back to top