Atovaquone + Proguanil
Indications
Atovaquone + Proguanil is used for:
Malaria
Adult Dose
Malaria
Prophylaxis
250 mg/100 mg (1 tablet) PO daily, beginning 1-2 days before travel to malaria-endemic area and continued until 7 days after return
Treatment
1 g/400 mg (4 tablets) PO daily for 3 days
Child Dose
Malaria
Prophylaxis
<11 kg: Safety and efficacy not established
11-20 kg: 62.5 mg/25 mg (1 pediatric tablet) PO daily
21-30 kg: 125 mg/50 mg (2 pediatric tablets) PO daily
31-40 kg: 187.5 mg/75 mg (3 pediatric tablets) PO daily
>40 kg: 250 mg/100 mg (1 adult tablet) PO daily, beginning 1-2 days before travel to malaria-endemic area and continued until 7 days after return
Treatment
<5 kg: Safety and efficacy not established
5-8 kg: 125 mg/50 mg (2 pediatric tablets) PO daily for 3 days
9-10 kg: 187.5 mg/75 mg (3 pediatric tablets) PO daily for 3 days
11-20 kg: 250 mg/100 mg (1 adult tablet) PO daily for 3 days
21-30 kg: 500 mg/200 mg (2 adult tablets) PO daily for 3 days
31-40 kg: 750 mg/300 mg (3 adult tablets) PO daily for 3 days
>40 kg: 1 g/400 mg (4 adult tablets) PO daily for 3 days
Renal Dose
CrCl <30 mL/min: Prophylactic use not recommended; only use for treatment if benefits of therapy greatly outweigh risks
CrCl 30-80 mL/min: No dosage adjustments necessary
Administration
Take at same time daily with food or milky drink
For children with difficulty swallowing, may be crushed and mixed with condensed milk just before administration
Contra Indications
Hypersensitivity
Not to be used for prophylaxis of Plasmodium falciparum in severe renal impairment
Precautions
Administration does not provide radical cure, nor does it prevent delayed primary attacks of P vivax and P ovale
Patients with severe malaria are not candidates for oral therapy; not evaluated in treatment of cerebral malaria or severe manifestations of malaria (eg, hyperparasitemia, pulmonary edema, renal failure)
Elevated LFTs and rare cases of hepatitis have been reported
Absorption may be reduced in patients with diarrhea or vomiting; monitor closely, and consider antiemetic use
Monotherapy may result in parasite relapse of P vivax malaria
Recrudescent P falciparum infection or chemoprophylactic failure after monotherapy should be treated with different schizonticide
Prophylaxis should not be prematurely discontinued
Complete prophylaxis includes therapy, protective clothing, insect repellents, and bednets
No chemoprophylactic regimen is 100% effective; patient should seek medical care for any febrile illness that occurs
P falciparum malaria carries higher risk of death and serious complications in pregnant women; patient should discuss risks and benefits of travel, and if travel cannot be avoided, additional prophylaxis, including protective clothing, must be employed
Pregnancy-Lactation
Pregnancy category: C
Lactation: Proguanil is excreted into milk in small quantities, but excretion of atovaquone is unknown; use with caution
Interactions
Adverse Effects
Side effects of Atovaquone + Proguanil :
>10%
Abdominal pain (3-31%)
Transaminase increases (17-27%)
Headache (3-14%)
Vomiting (1-13%)
Nausea (12%)
1-10%
Asthenia (8%)
Diarrhea (1-8%)
Pruritus (6%)
Anorexia (5%)
Dizziness (5%)
Dyspepsia (1-4%)
Gastritis (0-3%)
<1%
Fever
Cough
Mechanism of Action
Antiparasitic activity
Atovaquone: Selective inhibitor of parasite mitochondrial electron transport
Proguanil: Primary effect through metabolite cycloguanil, a dihydrofolate reductase inhibitor in malaria parasite, which leads to disruption of deoxythymidylate synthesis