Adult: Each tab contains atovaquone 250 mg and proguanil HCl 100 mg: >40 kg: 1 tab daily. Commence 24 hr or 48 hr prior to entering a malaria-endemic area; continue during the period of stay; and continue for 7 days after leaving the area. Child: Each tab contains atovaquone 62.5 mg and proguanil HCl 25 mg: 11-20 kg: 1 tab daily; 21-30 kg: 2 tab as a single dose daily; 31-40 kg: 3 tab as a single dose daily; >40 kg: Same as adult dose. Commence 24 hr or 48 hr prior to entering a malaria-endemic area; continue during the period of stay; and continue for 7 days after leaving the area.
Oral Acute uncomplicated falciparum malaria
Adult: Each tab contains atovaquone 250 mg and proguanil HCl 100 mg: 4 tab as a single dose for 3 consecutive days. Child: Each tab contains atovaquone 62.5 mg and proguanil HCl 25 mg: 5-8 kg: 2 tab as a single dose daily; 9-10 kg: 3 tabs as a single dose daily. Each tab contains atovaquone 250 mg and proguanil HCl 100 mg: 11-20 kg: 1 tab daily; 21-30 kg: 2 tab daily; 31-40 kg: 3 tab daily; >40 kg: Same as adult dose. All doses to be taken for 3 consecutive days.
Renal Impairment
Prophylaxis of Falciparum malaria:
CrCl (mL/min)
Dosage
<30
Contraindicated.
Administration
Should be taken with food. Take w/ meals or a milky drink.
Contraindications
Prophylactic use in severe renal impairment (CrCl <30 mL/min).
Special Precautions
Patient w/ diarrhoea or vomiting. Not intended for cerebral malaria or other severe manifestations of complicated malaria. Renal impairment. Pregnancy and lactation.
This drug may cause dizziness, if affected, do not drive or operate heavy machinery.
Monitoring Parameters
Monitor renal and hepatic function.
Drug Interactions
Reduced plasma concentrations of atovaquone w/ rifampicin, rifabutin, metoclopramide, tetracycline, efavirenz or boosted protease inhibitors. Proguanil may potentiate effect of warfarin and other coumarin based anticoagulants, leading to increased risk of haemorrhage.
Food Interaction
Admin w/ dietary fat increases the rate and extent of GI absorption of atovaquone.
Action
Description: Mechanism of Action: Atovaquone is a hydroxynaphthoquinone derivative, which selectively inhibits mitochondrial electron transport, reduces pyrimidine biosynthesis and collapses mitochondrial membrane potential in plasmodia, thus preventing parasite replication. Proguanil is a biguanide derivative; its metabolite, cycloguanil inhibits dihydrofolate reductase leading to depletion of pyrimidine nucleotide pools and disruption in nucleic acid synthesis and cell replication in plasmodia. The antimalarial activity of atovaquone and proguanil is synergistic against erythrocytic stages of the parasite. Pharmacokinetics: Absorption: Atovaquone: Bioavailability (w/ food): 23% (tab); 47% (liq). Increased rate and extent of GI absorption w/ dietary fat. Proguanil: Extensively absorbed from GI tract. Distribution: Atovaquone: Volume of distribution: Approx 8.8 L/kg. Plasma protein binding: >99%. Proguanil: Volume of distribution: 20-42 L/kg. Plasma protein binding: 75%. Metabolism: Proguanil: Partially metabolised primarily by CYP2C19 isoenzyme to cycloguanil and 4-chlorophenylbiguanide. Excretion: Atovaquone: Via faeces, >90% as unchanged drug. Elimination half-life: 2-3 days. Proguanil: Via urine, <40% as unchanged drug and metabolites. Elimination half-life: 12-15 hr (proguanil and cycloguanil).
Chemical Structure
Atovaquone Source: National Center for Biotechnology Information. PubChem Database. Atovaquone, CID=74989, https://pubchem.ncbi.nlm.nih.gov/compound/Atovaquone (accessed on Jan. 21, 2020)
Proguanil Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 6178111, Proguanil. https://pubchem.ncbi.nlm.nih.gov/compound/Proguanil. Accessed Feb. 27, 2023.
Anon. Atovaquone and Proguanil. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 03/03/2016.Buckingham R (ed). Atovaquone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/03/2016.Buckingham R (ed). Proguanil Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/03/2016.Joint Formulary Committee. Atovaquone with Proguanil Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/03/2016.McEvoy GK, Snow EK, Miller J et al (eds). Atovaquone and Proguanil Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 03/03/2016.
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