Atovaquone + proguanil
Antimalarials
Antimalarials
Daily oral combination for malaria prevention in travellers and for uncomplicated P. falciparum; taken with food or milk, avoided in severe kidney disease.
Quick facts
- Group
- Antimalarials
- Target
- Parasite mitochondrial cytochrome bc1 complex, Qo site (atovaquone); parasite dihydrofolate reductase (cycloguanil, from proguanil)
- Used for
- Treatment of uncomplicated P
- Key effects
- Nausea · Headache and dizziness · Cough
- Monitor
- Clinical response · Kidney function before prophylaxis
- ATC
- P01BB51
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows atovaquone bound to the Qo site of cytochrome bc1 from yeast (Saccharomyces cerevisiae), a model of the parasite complex.
Two drugs that act together. Atovaquone imitates ubiquinone and binds the Qo site of the parasite's cytochrome bc1 complex in the mitochondrion: electron transport stops, the membrane potential collapses and the parasite can no longer make pyrimidines. Proguanil itself enhances that mitochondrial effect, and its metabolite cycloguanil inhibits parasite dihydrofolate reductase. It acts on blood stages and on the early liver stage of P. falciparum, but not on P. vivax hypnozoites. Proguanil makes resistance to atovaquone much less likely.
- Atovaquone blocks the Qo site of cytochrome bc1
- Parasite mitochondria lose their membrane potential
- Proguanil boosts this; cycloguanil blocks DHFR
- Blood and early liver stages die
Indications
- Prophylaxis for travellers to malaria areas, including chloroquine-resistant areas Malaria →
- Treatment of uncomplicated P. falciparum malaria (an alternative to artemether + lumefantrine) Malaria →
Adverse effects
Common
- Nausea, vomiting, diarrhoea and abdominal pain
- Headache and dizziness
- Mouth sores and loss of appetite
- Cough
- Sun sensitivity of the skin
Contraindications
- Hypersensitivity to atovaquone or proguanil
- Severe kidney impairment (for prophylaxis)
- Not used alone in travellers with hyperparasitaemia; not recommended in pregnancy or for infants under the weight limit because of limited data
Key interactions
- Rifampicin and rifabutin
- Lower atovaquone levels
- Tetracycline
- Lowers atovaquone concentrations
- Efavirenz, lopinavir-ritonavir and atazanavir-ritonavir
- Markedly lower atovaquone and proguanil exposure; efficacy may be compromised
What is monitored
- Clinical response and blood smears when used as treatment (early failures can occur)
- Kidney function before prophylaxis in older people or kidney disease
- Vomiting after doses
- Skin and liver symptoms
Administration and safety
- Oral, once daily at the same time, with food or a milky drink.
- Prophylaxis starts a day or two before travel, continues during the stay and for 7 days after leaving.
- Adult and paediatric tablets differ: check the strength dispensed.
- If vomiting occurs soon after a dose, the prescriber decides whether to repeat it.
Pregnancy and breastfeeding
Not listed for pregnancy because safety data are insufficient; it may be considered when other options cannot be used.
Nursing care
- Before: kidney function, pregnancy status and other medicines (antiretrovirals, rifamycins).
- Teaching: take it with food or milk every day and keep taking it for a week after leaving the malaria area.
- Advise sun protection and repellents and bed nets; no drug prevents malaria completely.
- Fever during or after travel is an emergency: seek a malaria test at once.
Pharmacokinetics
- Absorption
- Atovaquone: slow and variable, much better with fatty food; proguanil: slow but adequate
- Distribution
- Atovaquone more than 99 % bound to plasma proteins
- Metabolism
- Proguanil is oxidised by liver CYP2C enzymes to active cycloguanil; atovaquone shows double blood peaks, suggesting enterohepatic cycling
Test yourself
Think of the answer, then tap the question to see it.
On which parasite structure does atovaquone act?
The Qo site of the mitochondrial cytochrome bc1 complex: electron transport stops and the mitochondrial membrane potential collapses.
Why is proguanil combined with atovaquone?
Proguanil enhances atovaquone's mitochondrial effect and greatly reduces the emergence of atovaquone resistance, which arises easily when atovaquone is used alone.
How long is it continued after leaving a malaria area, and why so short?
Seven days, because it also kills the early liver stage of P. falciparum, unlike drugs that only act on blood stages.
Connections
← Back to the class: Antimalarials
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Atovaquone and Proguanil: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); Treatment of Uncomplicated Malaria (Centers for Disease Control and Prevention (CDC), 2026); Adopción Parcial de Guía de Práctica Clínica Diagnóstico y tratamiento de la malaria, OMS 2022. Guía para Colombia, GPC #67-2022 (Ministerio de Salud y Protección Social (Colombia), 2022).
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Representative model, for educational purposes only.