Antimalarial (combination)
Atovaquone + proguanil (Malarone) is a combination antimalarial used for the prevention (prophylaxis) and treatment of Plasmodium falciparum malaria, including areas with chloroquine resistance. The two active ingredients work together, blocking different steps of the parasite life cycle. It should be taken with food or milk to improve absorption, and only with medical advice appropriate for the travel destination.
Also known as: Malarone
Proguanil may enhance the anticoagulant effect of Warfarin.
Atovaquone is very highly protein-bound (over 99%) and, by competing for the same binding sites, can displace warfarin and increase the active free fraction, with a transient INR rise. Proguanil does not appear to contribute significantly, but the two are used together. The effect is usually modest and transient, but in patients with a borderline INR it can trigger bleeding. The INR should be monitored at the start and end of prophylaxis and the dose adjusted if necessary.
Atovaquone is extensively protein-bound and can displace warfarin, transiently raising the INR. Monitor the INR when starting and stopping antimalarial prophylaxis.
Possible interaction with hepatic Warfarin metabolism.
INR and signs of bleeding.
Bleeding, bruising, dark stools.
Monitor the INR on starting/stopping and adjust the dose.
DailyMed/FDA (NIH/NLM) — approved Atovaquone + Proguanil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc22e8d8-3bfb-4f70-a599-dd81262a4887 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Alcohol may worsen the gastrointestinal effects of atovaquone + proguanil; limit intake.
Limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Atovaquone + Proguanil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc22e8d8-3bfb-4f70-a599-dd81262a4887
Taking with food (or milk) increases atovaquone absorption (2–3-fold) and is recommended to optimise efficacy.
Take with food or milk, preferably at the same daily meal.
DailyMed/FDA (NIH/NLM) — approved Atovaquone + Proguanil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc22e8d8-3bfb-4f70-a599-dd81262a4887
Proguanil is metabolised in the liver; in liver disease exposure may increase and requires caution.
Use with caution in liver disease.
DailyMed/FDA (NIH/NLM) — approved Atovaquone + Proguanil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc22e8d8-3bfb-4f70-a599-dd81262a4887
Atovaquone is not dialysable and its excretion depends on the biliary route; in severe renal impairment (CrCl < 30 ml/min) prophylaxis is not recommended and treatment requires caution.
Avoid prophylaxis in CrCl < 30 ml/min; use with caution for treatment.
DailyMed/FDA (NIH/NLM) — approved Atovaquone + Proguanil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc22e8d8-3bfb-4f70-a599-dd81262a4887
Atovaquone + proguanil may be used for malaria treatment in pregnancy when the benefit justifies it; it is not recommended as prophylaxis in pregnancy.
Use for treatment only if the benefit outweighs the risk; prefer another prophylaxis in pregnancy.
Excreted into breast milk in small amounts; compatible with breastfeeding under supervision.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Atovaquone + Proguanil label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fc22e8d8-3bfb-4f70-a599-dd81262a4887
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Combination antimalarial (atovaquone + proguanil) with synergistic action against P. falciparum, including chloroquine-resistant strains; used for prophylaxis and treatment of uncomplicated malaria.
Atovaquone is a ubiquinone analogue that selectively inhibits complex III of the plasmodial mitochondrial electron transport chain; proguanil (prodrug → cycloguanil via CYP2C19) inhibits the parasite dihydrofolate reductase. The combination is synergistic (sequential blockade).
Atovaquone is lipophilic with low aqueous solubility — highly variable absorption; with food (fat) AUC increases 2-3x and Cmax 5x; absolute bioavailability with food 23%; protein binding >99% (atovaquone) and 75% (proguanil).
Atovaquone: limited metabolism (no specific metabolite identified), faecal excretion >94% unchanged over 21 days and <0.6% urinary. Proguanil: metabolised to cycloguanil (CYP2C19) and 4-chlorophenylbiguanide; 40-60% excreted renally (adjust in renal impairment).
Elimination half-life ~2-3 days (atovaquone) and 12-21 h (proguanil, longer in slow metabolisers); volume of distribution ~8.8 L/kg (atovaquone).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
