Atovaquone/proguanil in malaria prophylaxis

Summary:

Atovaquone/proguanil in malaria prophylaxis

• acts as a causal prophylactic agent
• had very good efficacy against chloroquine-resistant P. falciparum
• the information relating to efficacy against P. vivax and other species is more limited (1)
• there is a relatively low incidence of adverse effects with this combination - there is evidence that atovaquone-proguanil caused fewer gastrointestinal adverse events than chloroquine-proguanil in travellers who were not immune to malaria (1)
• the half-life of this combination is 17 hours for proguanil and 2-3 days for atovaquone
• this combination treatment requires daily dosage - proguanil 100 mg plus atovaquone 250 mg
• started 1-2 days before entering a malarious area, should continue daily throughout the stay and for 7 days after leaving malaria endemic area
• contraindications include pregnancy

Mode of action

• atovaquone works by inhibiting electron transport in the mitochondrial cytochrome b-c1 complex, causing collapse in the mitochondrial membrane potential. This action is potentiated by proguanil and is not dependent upon conversion to its metabolite cycloguanil. Indeed, the combination remains effective in cycloguanil-resistant parasites
  
  
• atovaquone/proguanil prevents development of pre-erythrocytic (liver) schizonts (but not hypnozoites). It acts as a causal prophylactic agent, so needs to be continued for only 7 days after leaving a malarious area
  
  
• also has activity against the erythrocytic stages of malaria parasites and is useful for treatment

Efficacy

• prophylactic efficacy against P. falciparum is 90% or more
  
  
• is less published data on protection against P. vivax, but data available indicate that atovaquone-proguanil is effective in the prevention of primary attacks of vivax malaria
  • however, like chloroquine-proguanil, mefloquine and doxycycline, it will not protect against hypnozoite-induced episodes of P. vivax (or P. ovale) malaria

Contraindications

• allergy to proguanil or atovaquone or to any of the other ingredients in the tablets
• renal impairment (avoid for malaria prophylaxis if eGFR less than 30 mL/minute/1.73 m2)

Cautions

• Atovaquone/proguanil should generally be avoided in pregnancy
  • PHE advises that if there are no other options, its use may be considered in the second and third trimesters after careful risk assessment. Inadvertent conception when using atovaquone/proguanil is not an indication to consider termination of the pregnancy, as no evidence of harm has emerged in data so far available
    
    
• Atovaquone/proguanil should generally be avoided in breast feeding
  
  
• diarrhoea or vomiting may reduce the absorption of atovaquone.

Interactions

• as for proguanil
  
  
• drugs: Plasma concentrations of atovaquone are reduced by rifabutin and rifampicin, most non-nucleoside reverse transcriptase inhibitors, boosted protease inhibitors of HIV, tetracycline and metoclopramide (possible therapeutic failure of atovaquone, avoid concomitant use)
  
  
• Atovaquone interacts with some antiretroviral drugs. For up to date information and an Interaction Checker see https://www.hiv-druginteractions.org/
  
  
• Vaccines: None reported

Side-effects

• most frequent side-effects are headache and gastrointestinal upsets

The summary of product characteristics must be consulted before prescribing any of the drugs mentioned.

Reference

1. UK Health Security Agency. Malaria prevention guidelines for travellers from the UK (online). Last updated April 2025