Atovaquone + Proguanil

Malaria

Adults: Malaria Prophylaxis 250 mg/100 mg (1 tablet) Start prophylaxis 1 or 2 days before entering a malaria-endemic area and continue daily during the stay and for 7 days after return. One adult strength tablet per day. Treatment 1 g/400 mg (4 tablets): Four adult-strength tablets as a single daily dose for 3 days.

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

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

In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, the higher systemic exposure to cycloguanil, and the greater frequency of concomitant disease or other drug therapy.

No dosage adjustments are needed in patients with mild or moderate hepatic impairment. No trials have been conducted in patients with severe hepatic impairment.

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

Hypersensitivity Not to be used for prophylaxis of Plasmodium falciparum in severe renal impairment

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

C Pregnancy category: C Lactation: Proguanil is excreted into milk in small quantities, but excretion of atovaquone is unknown; use with caution

Administration with rifampin or rifabutin is known to reduce atovaquone concentrations; concomitant use with Atovaquone + Proguanil is not recommended. Proguanil may potentiate the anticoagulant effect of warfarin and other coumarin-based anticoagulants. Caution is advised when initiating or withdrawing Atovaquone + Proguanil in patients on anticoagulants; coagulation tests should be closely monitored. Tetracycline may reduce atovaquone concentrations; parasitemia should be closely monitored. Contraindicated (0) Serious - Use Alternative (2) dapsone topical efavirenz

>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

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