Atovaquone + Proguanil


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : PO Prophylaxis of Falciparum malaria Each tab contains atovaquone 250 mg and proguanil HCl 100 mg: >40 kg: 1 tab/day. 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. Acute uncomplicated falciparum malaria Each tab contains atovaquone 250 mg and proguanil HCl 100 mg: 4 tab as a single dose for 3 consecutive days.
Dosage Details
Oral
Prophylaxis of falciparum malaria
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.
Adverse Reactions
Abdominal pain, headache, anorexia, nausea, vomiting, diarrhoea, coughing, dizziness, asthenia, dreams, oral ulcers, pruritus.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate heavy machinery.
MonitoringParameters
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: 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

Chemical Structure Image
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)


Chemical Structure Image
Proguanil

Source: National Center for Biotechnology Information. PubChem Database. Proguanil, CID=6178111, https://pubchem.ncbi.nlm.nih.gov/compound/Proguanil (accessed on Jan. 21, 2020)

Storage
Store at 25°C.
MIMS Class
References
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.

Disclaimer: This information is independently developed by MIMS based on Atovaquone + Proguanil from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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