atovaquone/proguanil in malaria prophylaxis

Last edited 12/2019 and last reviewed 02/2023

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:

• Public Health England. Guidelines for malaria prevention in travellers from the UK 2019.