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